Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Fetal Programming and Cardiovascular Pathology

Barbara T. Alexander, John Henry Dasinger, Suttira Intapad

10.1002/cphy.c140036

Source: Volume 5, Issue 2, April 2015

Published online: March 2015

Full Article on Wiley Online Library



ABSTRACT

Low birth weight serves as a crude proxy for impaired growth during fetal life and indicates a failure for the fetus to achieve its full growth potential. Low birth weight can occur in response to numerous etiologies that include complications during pregnancy, poor prenatal care, parental smoking, maternal alcohol consumption, or stress. Numerous epidemiological and experimental studies demonstrate that birth weight is inversely associated with blood pressure and coronary heart disease. Sex and age impact the developmental programming of hypertension. In addition, impaired growth during fetal life also programs enhanced vulnerability to a secondary insult. Macrosomia, which occurs in response to maternal obesity, diabetes, and excessive weight gain during gestation, is also associated with increased cardiovascular risk. Yet, the exact mechanisms that permanently change the structure, physiology, and endocrine health of an individual across their lifespan following altered growth during fetal life are not entirely clear. Transmission of increased risk from one generation to the next in the absence of an additional prenatal insult indicates an important role for epigenetic processes. Experimental studies also indicate that the sympathetic nervous system, the renin angiotensin system, increased production of oxidative stress, and increased endothelin play an important role in the developmental programming of blood pressure in later life. Thus, this review will highlight how adverse influences during fetal life and early development program an increased risk for cardiovascular disease including high blood pressure and provide an overview of the underlying mechanisms that contribute to the fetal origins of cardiovascular pathology. © 2015 American Physiological Society. Compr Physiol 5:997‐1025, 2015.

Comprehensive Physiology offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images


Figure 1. Figure 1. Relationship between offspring of women with pre‐eclampsia and systolic blood pressure. (Used, with permission, Fig. 1, 35.)
Figure 2. Figure 2. Measure of MAP in a rat model of IUGR induced by reduced uterine perfusion. Data shown is for both male and female IUGR versus control offspring, at 4, 8, and 12 weeks of age. *P < 0.05 versus male control; †P < 0.05 versus female control; ‡P < 0.01 versus control; and §P < 0.01 versus control. All data are mean ± SEM. (Used, with permission, Fig. 1, 3.)
Figure 3. Figure 3. Systolic and diastolic blood pressures in male offspring of control (◯, □) or lard‐fed dams (•, ▪) at 80, 180, and 360 days old (n = 6 for all groups at all‐time points). Data are expressed as night (N) and day (D) 12‐h averages over 7 days (1‐7). Values are mean ± SEM. (Used, with permission, Fig. 2, 95.)
Figure 4. Figure 4. Systolic and diastolic blood pressures in female offspring of control dams (◯, □) at 80 days (n = 6), 180 days (n = 5), and 360 days (n = 6) or lard‐fed dams (•, ▪) at 80 days (n = 6), 180 days (n = 5), and 360 days (n = 6). Data are expressed as night (N) and day (D) 12‐h averages over 7 days (1‐7). Values are mean ± SEM. *P < 0.05, **P < 0.01. (Used, with permission, Fig. 3, 95.)
Figure 5. Figure 5. Influence of current parental smoking on BP in preschool children (**P = 0.0001, *P < 0.05). The boundary of the box closest to zero indicates the 25th percentile, the line within the box marks the median, and the boundary of the box farthest from zero indicates the 75th percentile. Whiskers (error bars) above and below the box indicate the 90th and 10th percentiles. (Used, with permission, Fig. 1, 191.)
Figure 6. Figure 6. Effect of nicotine on Ang II‐induced BP response in adult male and female offspring. SBP, DBP, and MAP responses to Ang II (10 μg/kg) were measured in adult male and female offspring that had been exposed in utero to saline control or nicotine. Data are means ± SEMs and were analyzed by two‐way ANOVA with a post hoc test. *P < 0.05, nicotine versus control. (Used, with permission, Fig. 1, 249.)
Figure 7. Figure 7. The effect of chronic Ang II on blood pressure in male and female offspring exposed to early life stress (ELS) relative to control counterpart. ANG II‐induced hypertension is delayed and attenuated in female MatSep rats compared with control rats. B*P < 0.05 versus corresponding sex control group, #P < 0.05 versus corresponding male group. (Used, with permission, Fig. 1A, 114.)
Figure 8. Figure 8. Systolic blood pressures in 6‐month‐old rats that received prenatal dexamethasone or vehicle. Blood pressure was taken in trained rats using a tail cuff. Male rats (A) that received prenatal dexamethasone on days 13 and 14, 15 and 16, and 17 and 18 had elevated blood pressure compared with control rats. Female rats (B) were not hypertensive. There are at least 10 male rats in each group. There were eight female rats in each group except days 11 and 12 and days 19 and 20, in which there were five rats. (Used, with permission, Fig. 5, 151.)
Figure 9. Figure 9. The increase of daytime and nighttime SBP with age by ethnicity and gender. (Used, with permission, Fig. 1, 226.)
Figure 10. Figure 10. Serum testosterone levels measured in control and IUGR adult offspring. Blood collection followed decapitation at 16 weeks of age. Control intact (n = 17), IUGR intact (n = 16), control CTX (n = 16), and IUGR CTX (n = 15) *P < 0.05 versus control; †P < 0.05 versus intact counterpart. All data are expressed as means ± SE. (Used, with permission, Fig. 5, 145.)
Figure 11. Figure 11. The effect of castration on blood pressure in a rat model of intrauterine growth restriction (IUGR) induced by placental insufficiency. Mean arterial pressure (MAP) was measured by radio telemetry from 12 to 16 weeks of age in conscious, free‐moving animals that underwent either sham (intact) or castration (CTX) at 10 weeks of age. Control intact (n = 9), control CTX (n = 8), IUGR intact (n = 8), and IUGR CTX (n = 7). *P < 0.05 versus control intact; †P < 0.05 versus IUGR intact. All data are expressed as means ± SE. (Used, with permission, Fig. 1, 145.)
Figure 12. Figure 12. Arterial pressure and renal hemodynamics in adult intact male, castrated (CAS) male and female offspring of rats fed either a normal or protein‐restricted diet during pregnancy. Values are means ± SE. *P < 0.05 compared with value for intact males of same diet group. †P < 0.05 compared with value for CAS males. ‡P < 0.05 compared with normal protein animals of same sex group. (Used, with permission, Fig. 1, 243.)
Figure 13. Figure 13. Ovariectomy and blood pressure in IUGR offspring. MAP was measured by radiotelemetry from 12 to 16 weeks of age in animals that underwent either sham (intact) or OVX at 10 weeks of age. Control intact (n = 7), control OVX (n = 7), IUGR intact (n = 7), and IUGR OVX (n = 8). *P < 0.01 versus IUGR intact. All data are expressed as mean ± SEM. (Used, with permission, Fig. 1, 144.)
Figure 14. Figure 14. Effect of nicotine on angiotensin II (Ang II)–induced blood pressure (BP) response in sham, ovariectomy (OVX), and OVX+E2 offspring. Diastolic BP (DBP), systolic BP (SBP), and mean arterial BP (MAP) responses to Ang II (10 μg/kg) were measured in sham, OVX, and OVX+E2 groups of female offspring that had been exposed in utero to saline control or nicotine. All of the data are expressed as means ± SEM from six animals in each group. †P < 0.05 versus saline group; *P < 0.05 versus data points in saline group. (Used, with permission, Fig. 1, 251.)
Figure 15. Figure 15. Percentage (SE) postmenopausal by age 44 to 45 years by birthweight. (Used, with permission, Fig. 2, 215.)
Figure 16. Figure 16. The effect of renin‐angiotensin system (RAS) blockade with angiotensin converting enzyme (ACE) inhibition in adult male IUGR offspring. The ACE inhibitor enalapril was administrated at a dose of 250 mg/L via drinking water for 2 weeks starting at 14 weeks of age in IUGR offspring. MAP was measured by radio telemetry from 12 to 16 weeks of age in conscious and free‐moving animals that underwent either sham (intact) or castration (CTX) at 10 weeks of age. IUGR intact untreated (n = 8), IUGR CTX untreated (n = 7), IUGR intact treated (n = 8), IUGR CTX treated (n = 8). *P < 0.05 versus IUGR intact, †P < 0.05 versus IUGR intact; and ‡P < 0.05 versus IUGR CTX. All data are expressed as means ± SE. (Used, with permission, Fig. 2, 145.)
Figure 17. Figure 17. Renal ACE and ACE2 mRNA expression in intact and ovariectomized control and IUGR offspring. Renal ACE and ACE2 mRNA expressions were assessed using real‐time PCR. Results were calculated using the 2−ΔΔCT method and expressed in folds increase/decrease of the gene of interest; control‐intact (n = 7), IUGR‐intact (n = 7), control‐OVX (n = 7), and IUGR‐OVX (n = 8). *P < 0.05 versus control‐intact ACE2. †P < 0.05 versus IUGR‐intact ACE2. All of the data are expressed as mean ± SEM. (Used, with permission, Fig. 5, 144.)
Figure 18. Figure 18. Mean arterial pressure in female control and IUGR rats measured by (a) telemetry or (b) chronically instrumented catheters in the conscious state 2 weeks postbilateral renal denervation. *P < 0.05, †P < 0.01, ‡P < 0.001. Data values represent mean ± SE. (Used, with permission, Fig. 5, 84.)
Figure 19. Figure 19. Effect of prenatal dexamethasone and renal denervation on type 3 Na+/H+ exchanger (NHE3) protein abundance. (Used, with permission, Fig. 3, 32.)
Figure 20. Figure 20. Renal superoxide production and urinary excretion of F2‐isoprostanes in male and female control and intrauterine growth‐restricted (IUGR) offspring treated with the superoxide dismutase (SOD) mimetic Tempol (1 mmol/L) or vehicle (tap water ad libitum) from 14 weeks to 16 weeks of age. (A) 24‐h urinary excretion of F2‐isoprostane; (B) renal basal superoxide anion production; and (C) renal NADPH oxidase‐dependent superoxide anion production. *P < 0.05 versus untreated male control, #P < 0.05 versus untreated male IUGR, †P < 0.05 versus untreated male IUGR. Data values represent mean ± SE. □, control; ▪, IUGR. (Used, with permission, Fig. 3, 146.)
Figure 21. Figure 21. Effect of antenatal nicotine on vascular malondialdehyde (MDA) and superoxide dismutase (SOD) activities. Pregnant rats were treated with saline (control) or nicotine, MDA (A) and SOD activity (B) were determined in aortas isolated from 5‐month‐old male offspring. Data are means ± SEM of tissues from five animals. *P < 0.05 versus control. (Used, with permission, Fig. 4, 250.)
Figure 22. Figure 22. (A) Renal tubular injury scores in response to a mild I/R in NBW and LBW rats untreated and treated with tempol. The degree of tubular injury was scored using an established method of semiquantitive evaluation of 10 fields randomly selected per each examined kidney (high‐power fields). All data are expressed as means ± SE. *P < 0.005 versus all other groups. †P < 0.05 versus LBW untreated counterpart. (B) Microphotographs representing renal tubular injury in response to a mild I/R in NBW and LBW rats untreated and treated with tempol. (a) NBW sham. (b) LBW sham. (c) NBW mild renal I/R. (d) LBW mild renal I/R. (e) NBW mild renal I/R + tempol. (f) LBW mild renal I/R + tempol. (All pictures are hematoxylin and eosin at ×400 magnification. Scale bars = 50 μm.) (Used, with permission, Fig. 8, 143.)
Figure 23. Figure 23. Schematic diagram of the fetal programming of cardiovascular risk that originates from adverse exposure to maternal insults during gestational life and programs alterations in structure and physiology that contribute to the development of increased cardiovascular risk in later life.


Figure 1. Relationship between offspring of women with pre‐eclampsia and systolic blood pressure. (Used, with permission, Fig. 1, 35.)


Figure 2. Measure of MAP in a rat model of IUGR induced by reduced uterine perfusion. Data shown is for both male and female IUGR versus control offspring, at 4, 8, and 12 weeks of age. *P < 0.05 versus male control; †P < 0.05 versus female control; ‡P < 0.01 versus control; and §P < 0.01 versus control. All data are mean ± SEM. (Used, with permission, Fig. 1, 3.)


Figure 3. Systolic and diastolic blood pressures in male offspring of control (◯, □) or lard‐fed dams (•, ▪) at 80, 180, and 360 days old (n = 6 for all groups at all‐time points). Data are expressed as night (N) and day (D) 12‐h averages over 7 days (1‐7). Values are mean ± SEM. (Used, with permission, Fig. 2, 95.)


Figure 4. Systolic and diastolic blood pressures in female offspring of control dams (◯, □) at 80 days (n = 6), 180 days (n = 5), and 360 days (n = 6) or lard‐fed dams (•, ▪) at 80 days (n = 6), 180 days (n = 5), and 360 days (n = 6). Data are expressed as night (N) and day (D) 12‐h averages over 7 days (1‐7). Values are mean ± SEM. *P < 0.05, **P < 0.01. (Used, with permission, Fig. 3, 95.)


Figure 5. Influence of current parental smoking on BP in preschool children (**P = 0.0001, *P < 0.05). The boundary of the box closest to zero indicates the 25th percentile, the line within the box marks the median, and the boundary of the box farthest from zero indicates the 75th percentile. Whiskers (error bars) above and below the box indicate the 90th and 10th percentiles. (Used, with permission, Fig. 1, 191.)


Figure 6. Effect of nicotine on Ang II‐induced BP response in adult male and female offspring. SBP, DBP, and MAP responses to Ang II (10 μg/kg) were measured in adult male and female offspring that had been exposed in utero to saline control or nicotine. Data are means ± SEMs and were analyzed by two‐way ANOVA with a post hoc test. *P < 0.05, nicotine versus control. (Used, with permission, Fig. 1, 249.)


Figure 7. The effect of chronic Ang II on blood pressure in male and female offspring exposed to early life stress (ELS) relative to control counterpart. ANG II‐induced hypertension is delayed and attenuated in female MatSep rats compared with control rats. B*P < 0.05 versus corresponding sex control group, #P < 0.05 versus corresponding male group. (Used, with permission, Fig. 1A, 114.)


Figure 8. Systolic blood pressures in 6‐month‐old rats that received prenatal dexamethasone or vehicle. Blood pressure was taken in trained rats using a tail cuff. Male rats (A) that received prenatal dexamethasone on days 13 and 14, 15 and 16, and 17 and 18 had elevated blood pressure compared with control rats. Female rats (B) were not hypertensive. There are at least 10 male rats in each group. There were eight female rats in each group except days 11 and 12 and days 19 and 20, in which there were five rats. (Used, with permission, Fig. 5, 151.)


Figure 9. The increase of daytime and nighttime SBP with age by ethnicity and gender. (Used, with permission, Fig. 1, 226.)


Figure 10. Serum testosterone levels measured in control and IUGR adult offspring. Blood collection followed decapitation at 16 weeks of age. Control intact (n = 17), IUGR intact (n = 16), control CTX (n = 16), and IUGR CTX (n = 15) *P < 0.05 versus control; †P < 0.05 versus intact counterpart. All data are expressed as means ± SE. (Used, with permission, Fig. 5, 145.)


Figure 11. The effect of castration on blood pressure in a rat model of intrauterine growth restriction (IUGR) induced by placental insufficiency. Mean arterial pressure (MAP) was measured by radio telemetry from 12 to 16 weeks of age in conscious, free‐moving animals that underwent either sham (intact) or castration (CTX) at 10 weeks of age. Control intact (n = 9), control CTX (n = 8), IUGR intact (n = 8), and IUGR CTX (n = 7). *P < 0.05 versus control intact; †P < 0.05 versus IUGR intact. All data are expressed as means ± SE. (Used, with permission, Fig. 1, 145.)


Figure 12. Arterial pressure and renal hemodynamics in adult intact male, castrated (CAS) male and female offspring of rats fed either a normal or protein‐restricted diet during pregnancy. Values are means ± SE. *P < 0.05 compared with value for intact males of same diet group. †P < 0.05 compared with value for CAS males. ‡P < 0.05 compared with normal protein animals of same sex group. (Used, with permission, Fig. 1, 243.)


Figure 13. Ovariectomy and blood pressure in IUGR offspring. MAP was measured by radiotelemetry from 12 to 16 weeks of age in animals that underwent either sham (intact) or OVX at 10 weeks of age. Control intact (n = 7), control OVX (n = 7), IUGR intact (n = 7), and IUGR OVX (n = 8). *P < 0.01 versus IUGR intact. All data are expressed as mean ± SEM. (Used, with permission, Fig. 1, 144.)


Figure 14. Effect of nicotine on angiotensin II (Ang II)–induced blood pressure (BP) response in sham, ovariectomy (OVX), and OVX+E2 offspring. Diastolic BP (DBP), systolic BP (SBP), and mean arterial BP (MAP) responses to Ang II (10 μg/kg) were measured in sham, OVX, and OVX+E2 groups of female offspring that had been exposed in utero to saline control or nicotine. All of the data are expressed as means ± SEM from six animals in each group. †P < 0.05 versus saline group; *P < 0.05 versus data points in saline group. (Used, with permission, Fig. 1, 251.)


Figure 15. Percentage (SE) postmenopausal by age 44 to 45 years by birthweight. (Used, with permission, Fig. 2, 215.)


Figure 16. The effect of renin‐angiotensin system (RAS) blockade with angiotensin converting enzyme (ACE) inhibition in adult male IUGR offspring. The ACE inhibitor enalapril was administrated at a dose of 250 mg/L via drinking water for 2 weeks starting at 14 weeks of age in IUGR offspring. MAP was measured by radio telemetry from 12 to 16 weeks of age in conscious and free‐moving animals that underwent either sham (intact) or castration (CTX) at 10 weeks of age. IUGR intact untreated (n = 8), IUGR CTX untreated (n = 7), IUGR intact treated (n = 8), IUGR CTX treated (n = 8). *P < 0.05 versus IUGR intact, †P < 0.05 versus IUGR intact; and ‡P < 0.05 versus IUGR CTX. All data are expressed as means ± SE. (Used, with permission, Fig. 2, 145.)


Figure 17. Renal ACE and ACE2 mRNA expression in intact and ovariectomized control and IUGR offspring. Renal ACE and ACE2 mRNA expressions were assessed using real‐time PCR. Results were calculated using the 2−ΔΔCT method and expressed in folds increase/decrease of the gene of interest; control‐intact (n = 7), IUGR‐intact (n = 7), control‐OVX (n = 7), and IUGR‐OVX (n = 8). *P < 0.05 versus control‐intact ACE2. †P < 0.05 versus IUGR‐intact ACE2. All of the data are expressed as mean ± SEM. (Used, with permission, Fig. 5, 144.)


Figure 18. Mean arterial pressure in female control and IUGR rats measured by (a) telemetry or (b) chronically instrumented catheters in the conscious state 2 weeks postbilateral renal denervation. *P < 0.05, †P < 0.01, ‡P < 0.001. Data values represent mean ± SE. (Used, with permission, Fig. 5, 84.)


Figure 19. Effect of prenatal dexamethasone and renal denervation on type 3 Na+/H+ exchanger (NHE3) protein abundance. (Used, with permission, Fig. 3, 32.)


Figure 20. Renal superoxide production and urinary excretion of F2‐isoprostanes in male and female control and intrauterine growth‐restricted (IUGR) offspring treated with the superoxide dismutase (SOD) mimetic Tempol (1 mmol/L) or vehicle (tap water ad libitum) from 14 weeks to 16 weeks of age. (A) 24‐h urinary excretion of F2‐isoprostane; (B) renal basal superoxide anion production; and (C) renal NADPH oxidase‐dependent superoxide anion production. *P < 0.05 versus untreated male control, #P < 0.05 versus untreated male IUGR, †P < 0.05 versus untreated male IUGR. Data values represent mean ± SE. □, control; ▪, IUGR. (Used, with permission, Fig. 3, 146.)


Figure 21. Effect of antenatal nicotine on vascular malondialdehyde (MDA) and superoxide dismutase (SOD) activities. Pregnant rats were treated with saline (control) or nicotine, MDA (A) and SOD activity (B) were determined in aortas isolated from 5‐month‐old male offspring. Data are means ± SEM of tissues from five animals. *P < 0.05 versus control. (Used, with permission, Fig. 4, 250.)


Figure 22. (A) Renal tubular injury scores in response to a mild I/R in NBW and LBW rats untreated and treated with tempol. The degree of tubular injury was scored using an established method of semiquantitive evaluation of 10 fields randomly selected per each examined kidney (high‐power fields). All data are expressed as means ± SE. *P < 0.005 versus all other groups. †P < 0.05 versus LBW untreated counterpart. (B) Microphotographs representing renal tubular injury in response to a mild I/R in NBW and LBW rats untreated and treated with tempol. (a) NBW sham. (b) LBW sham. (c) NBW mild renal I/R. (d) LBW mild renal I/R. (e) NBW mild renal I/R + tempol. (f) LBW mild renal I/R + tempol. (All pictures are hematoxylin and eosin at ×400 magnification. Scale bars = 50 μm.) (Used, with permission, Fig. 8, 143.)


Figure 23. Schematic diagram of the fetal programming of cardiovascular risk that originates from adverse exposure to maternal insults during gestational life and programs alterations in structure and physiology that contribute to the development of increased cardiovascular risk in later life.
References
 1. Aagaard‐Tillery KM , Grove K , Bishop J , Ke X , Fu Q , McKnight R , Lane RH . Developmental origins of disease and determinants of chromatin structure: Maternal diet modifies the primate fetal epigenome. J Mol Endocrinol 41: 91‐102, 2008. doi: 10.1677/JME‐08‐0025.
 2. Aceti A , Santhakumaran S , Logan KM , Philipps LH , Prior E , Gale C , Hyde MJ , Modi N . The diabetic pregnancy and offspring blood pressure in childhood: A systematic review and meta‐analysis. Diabetologia 55: 3114‐3127, 2012. doi: 10.1007/s00125‐012‐2689‐8.
 3. Alexander BT . Placental insufficiency leads to development of hypertension in growth‐restricted offspring. Hypertension 41: 457‐462, 2003.
 4. Alexander BT , Hendon AE , Ferril G , Dwyer TM . Renal denervation abolishes hypertension in low‐birth‐weight offspring from pregnant rats with reduced uterine perfusion. Hypertension 45: 754‐758, 2005.
 5. American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol 122: 1122‐1131, 2013.
 6. Anderson CM , Lopez F , Zimmer A , Benoit JN . Placental insufficiency leads to developmental hypertension and mesenteric artery dysfunction in two generations of Sprague‐Dawley rat offspring. Biol Reprod 74: 538‐544, 2006.
 7. Andersen LG , Angquist L , Eriksson JG , Forsen T , Gamborg M , Osmond C , Baker JL , Sorensen TI . Birth weight, childhood body mass index and risk of coronary heart disease in adults: Combined historical cohort studies. PLoS One 5: e14126, 2010. doi: 10.1371/journal.pone.0014126.
 8. Barker D. Mother, Babies, and Disease in Later Life. London: BMJ Publishing Group, 1994, pp. 1‐12 and 132‐134.
 9. Barker DJ , Osmond C . Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet 1: 1077‐1081, 1986.
 10. Barker DJ , Osmond C . Low birth weight and hypertension. BMJ 297: 134‐135, 1988.
 11. Baserga M , Kaur R , Hale MA , Bares A , Yu X , Callaway CW , McKnight RA , Lane RH . Fetal growth restriction alters transcription factor binding and epigenetic mechanisms of renal 11beta‐hydroxysteroid dehydrogenase type 2 in a sex‐specific manner. Am J Physiol Regul Integr Comp Physiol 299: R334‐R342, 2010. doi: 10.1152/ajpregu.00122.2010.
 12. Ben‐Shlomo Y , McCarthy A , Hughes R , Tilling K , Davies D , Smith GD . Immediate postnatal growth is associated with blood pressure in young adulthood: The Barry Caerphilly Growth Study. Hypertension 52: 638‐644, 2008. doi: 10.1161/HYPERTENSIONAHA.108.114256
 13. Bercovich E , Keinan‐Boker L , Shasha SM . Long‐term health effects in adults born during the Holocaust. Isr Med Assoc J 16: 203‐207, 2014.
 14. Bernal AB , Vickers MH , Hampton MB , Poynton RA , Sloboda DM . Maternal undernutrition significantly impacts ovarian follicle number and increases ovarian oxidative stress in adult rat offspring. PLoS One 5: e15558, 2010. doi: 10.1371/journal.pone.0015558.
 15. Black MJ , Sutherland MR , Gubhaju L , Kent AL , Dahlstrom JE , Moore L . When birth comes early: Effects on nephrogenesis. Nephrology (Carlton) 18: 180‐182, 2013. doi: 10.1111/nep.12028.
 16. Bogdarina I , Haase A , Langley‐Evans S , Clark AJ . Glucocorticoid effects on the programming of AT1b angiotensin receptor gene methylation and expression in the rat. PLoS One 5: e9237, 2010. doi: 10.1371/journal.pone.0009237.
 17. Boguszewski MC , Johannsson G , Fortes LC , Sverrisdóttir YB . Low birth size and final height predict high sympathetic nerve activity in adulthood. J Hypertens 22: 1157‐1163, 2004.
 18. Boney CM , Verma A , Tucker R , Vohr BR . Metabolic syndrome in childhood: Association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 115: e290‐e296, 2005.
 19. Börzsönyi B , Demendi C , Pajor A , Rigó J Jr , Marosi K , Agota A , Nagy ZB , Joó JG . Gene expression patterns of the 11β‐hydroxysteroid dehydrogenase 2 enzyme in human placenta from intrauterine growth restriction: The role of impaired feto‐maternal glucocorticoid metabolism. Eur J Obstet Gynecol Reprod Biol 161: 12‐17, 2012. doi: 10.1016/j.ejogrb.2011.
 20. Boubred F , Saint‐Faust M , Buffat C , Ligi I , Grandvuillemin I , Simeoni U . Developmental origins of chronic renal disease: An integrative hypothesis. Int J Nephrol 2013: 346067, 2013. PMID: 24073334. doi: 10.1155/2013/346067.
 21. Bourque SL , Gragasin FS , Quon AL , Mansour Y , Morton JS , Davidge ST . Prenatal hypoxia causes long‐term alterations in vascular endothelin‐1 function in aged male, but not female, offspring. Hypertension 62: 753‐758, 2013. doi: 10.1161/HYPERTENSIONAHA.113.01516.
 22. Breukhoven PE , Kerkhof GF , Willemsen RH , Hokken‐Koelega AC . Fat mass and lipid profile in young adults born preterm. J Clin Endocrinol Metab 97: 1294‐1302, 2012. doi: 10.1210/jc.2011‐2621.
 23. Bromberger JT , Matthews KA , Kuller LH , Wing RR , Meilahn EN , Plantinga P . Prospective study of the determinants of age at menopause. Am J Epidemiol 145: 124‐133, 1997.
 24. Bruin JE , Kellenberger LD , Gerstein HC , Morrison KM , Holloway AC . Fetal and neonatal nicotine exposure and postnatal glucose homeostasis: Identifying critical windows of exposure. J Endocrinol 194: 171‐178, 2007.
 25. Burdge GC , Lillycrop KA . Nutrition, epigenetics, and developmental plasticity: Implications for understanding human disease. Annu Rev Nutr 30: 315‐339, 2010. doi: 10.1146/annurev.nutr.012809.104751.
 26. Cambonie G , Comte B , Yzydorczyk C , Ntimbane T , Germain N , Lê NL , Pladys P , Gauthier C , Lahaie I , Abran D , Lavoie JC , Nuyt AM . Antenatal antioxidant prevents adult hypertension, vascular dysfunction, and microvascular rarefaction associated with in utero exposure to a low‐protein diet. Am J Physiol Regul Integr Comp Physiol 292: R1236‐R1245, 2007.
 27. Carlsson S , Persson PG , Alvarsson M , Efendic S , Norman A , Svanström L , Ostenson CG , Grill V . Low birth weight, family history of diabetes, and glucose intolerance in Swedish middle‐aged men. Diabetes Care 22: 1043‐1047, 1999.
 28. Chernoff N , Gage MI , Stoker TE , Cooper RL , Gilbert ME , Rogers EH . Reproductive effects of maternal and pre‐weaning undernutrition in rat offspring: Age at puberty, onset of female reproductive senescence and intergenerational pup growth and viability. Reprod Toxicol 28: 489‐494, 2009. doi: 10.1016/j.reprotox.2009.06.006
 29. Cunningham FG , Gant NF , Leveno KJ , Gilstrap LC III, Hauth JC, Wenstrom KD. Diabetes. In: Cunningham FG , Gant NF , Leveno KJ , et al., eds. Williams Obstetrics. 21st ed. New York, NY: McGraw‐Hill, 2001, pp. 1359‐1381.
 30. Curhan GC , Chertow GM , Willett WC , Spiegelman D , Colditz GA , Manson JE , Speizer FE , Stampfer MJ . Birth weight and adult hypertension and obesity in women. Circulation 94: 1310‐1315, 1996.
 31. Curhan GC , Willett WC , Rimm EB , Spiegelman D , Ascherio AL , Stampfer MJ . Birth weight and adult hypertension, diabetes mellitus, and obesity in US men. Circulation 94: 3246‐3250, 1996.
 32. Dagan A , Kwon HM , Dwarakanath V , Baum M . Effect of renal denervation on prenatal programming of hypertension and renal tubular transporter abundance. Am J Physiol Renal Physiol 295: F29‐F34, 2008. doi: 10.1152/ajprenal.00123.2008.
 33. Dalziel SR , Parag V , Rodgers A , Harding JE . Cardiovascular risk factors at age 30 following pre‐term birth. Int J Epidemiol 36: 907‐915, 2007.
 34. Davies AA , Smith GD , Ben‐Shlomo Y , Litchfield P . Low birth weight is associated with higher adult total cholesterol concentration in men: Findings from an occupational cohort of 25,843 employees. Circulation 110: 1258‐1262, 2004.
 35. Davis EF , Lazdam M , Lewandowski AJ , Worton SA , Kelly B , Kenworthy Y , Adwani S , Wilkinson AR , McCormick K , Sargent I , Redman C , Leeson P . Cardiovascular risk factors in children and young adults born to preeclamptic pregnancies: A systematic review. Pediatrics 129: e1552‐e1561, 2012. doi: 10.1542/peds.2011‐3093.
 36. De B , Lin S , Lohsoonthorn V , Williams MA . Risk of preterm delivery in relation to maternal low birth weight. Acta Obstet Gynecol Scand 86: 565‐571, 2007.
 37. de Almeida Chaves Rodrigues AF , de Lima IL , Bergamaschi CT , Campos RR , Hirata AE , Schoorlemmer GH , Gomes GN . Increased renal sympathetic nerve activity leads to hypertension and renal dysfunction in offspring from diabetic mothers. Am J Physiol Renal Physiol 304: F189‐F197, 2013. doi: 10.1152/ajprenal.00241.2012.
 38. de Jong F , Monuteaux MC , van Elburg RM , Gillman MW , Belfort MB . Systematic review and meta‐analysis of preterm birth and later systolic blood pressure. Hypertension 59: 226‐234, 2012. doi: 10.1161/HYPERTENSIONAHA.111.181784.
 39. de Rooij SR , Painter RC , Holleman F , Bossuyt PM , Roseboom TJ . The metabolic syndrome in adults prenatally exposed to the Dutch famine. Am J Clin Nutr 86: 1219‐1224, 2007.
 40. Desai M , Jellyman JK , Han G , Beall M , Lane RH , Ross MG . Rat maternal obesity and high‐fat program offspring metabolic syndrome. Am J Obstet Gunecol 2014 [Epub ahead of print] doi: 10.1016/j.ajog.2014.03.025.
 41. DiBona GF . Peripheral and central interactions between the renin angiotensin system and the sympathetic nerves in the control of renal function. Ann N Y Sci 940: 395‐406, 2001.
 42. Di Canni G , Miccoli R , Volpe L , Lencioni C , Del Prato S . Intermediate metabolism in normal pregnancy and in gestational diabetes. Diabetes Metab Res Rev 19: 259‐270, 2003.
 43. Dickinson H , Walker DW , Wintour EM , Moritz K . Maternal dexamethasone treatment at midgestation reduces nephron number and alters renal gene expression in the fetal spiny mouse. Am J Physiol Regul Integr Comp Physiol 292: R453‐R461, 2006.
 44. Dior UP , Lawrence GM , Sitlani C , Enquobahrie D , Manor O , Siscovick DS , Friedlander Y , Hochner H . Parental smoking during pregnancy and offspring cardio‐metabolic risk factors at ages 17 and 32. Atherosclerosis 235: 430‐437, 2014. doi: 10.1016/j.atherosclerosis.2014.05.937.
 45. Dodson RB , Rozance PJ , Fleenor BS , Petrash CC , Shoemaker LG , Hunter KS , Ferguson VL . Increased arterial stiffness and extracellular matrix reorganization in intrauterine growth‐restricted fetal sheep. Pediatr Res 73: 147‐154, 2013. doi: 10.1038/pr.2012.156.
 46. Dominguez TP . Adverse birth outcomes in African American women: The social context of persistent reproductive disadvantage. Soc Work Public Health 26: 3‐16, 2011. doi: 10.1080/10911350902986880.
 47. Dong M , Giles WH , Felitti VJ , Dube SR , Williams JE , Chapman DP , Anda RF . Insights into causal pathways for ischemic heart disease: Adverse childhood experiences study. Circulation 110: 1761‐1766, 2004.
 48. Drake AJ , Walker BR , Seckl JR . Intergenerational consequences of fetal programming by in utero exposure to glucocorticoids in rats. Am J Physiol Regul Integr Comp Physiol 288: R34‐R38, 2005.
 49. Elias SG , van Noord PA , Peeters PH , den Tonkelaar I , Grobbe DE . Caloric restriction reduces age at menopause: The effect of the 1944‐1945 Dutch famine. Menopause 10: 399‐405, 2003.
 50. Eriksson JG , Sandboge S , Salonen MK , Kajantie E , Osmond C . Long‐term consequences of maternal overweight in pregnancy on offspring later health: Findings from the Helsinki Birth Cohort Study. Ann Med 9: 1‐5, 2014.
 51. Esler M . The sympathetic system and hypertension. Am J Hypertens 13: 99S‐105S, 2000.
 52. Ferreira I , Peeters LL , Stehouwer CD . Preeclampsia and increased blood pressure in the offspring: Meta‐analysis and critical review of the evidence. J Hypertens 27: 1955‐1959, 2009. doi: 10.1097/HJH.0b013e328331b8c6.
 53. Filkaszova A , Chabada J , Stencl P , Drobny J , Sysak R , Urban H , Oravec J , Lamprechtova B , Oroszova V . Ultrasound diagnosis of macrosomia. Bratisl Lek Listy 115: 30‐33, 2014.
 54. Finken MJ , Keijzer‐Veen MG , Dekker FW , Frölich M , Hille ET , Romijn JA , Wit JM ; Dutch POPS‐19 Collaborative Study Group. Preterm birth and later insulin resistance: Effects of birth weight and postnatal growth in a population based longitudinal study from birth into adult life. Diabetologia 49: 478‐485, 2006.
 55. Forest JC , Girouard J , Masse J , Moutquin JM , Kharfi A , Ness RB , Roberts JM , Giquere Y . Early occurrence of metabolic syndrome after hypertension in pregnancy. Obstet Gynecol 105: 1373‐1380, 2005.
 56. Forsdahl A . Are poor living conditions in childhood and adolescence an important risk factor for arteriosclerotic heart disease? Br J Prev Soc Med 31: 91‐95, 1977.
 57. Franco MC , Akamine EH , Rebouças N , Carvalho MH , Tostes RC , Nigro D , Fortes ZB . Long‐term effects of intrauterine malnutrition on vascular function in female offspring: Implications of oxidative stress. Life Sci 80: 709‐715, 2007.
 58. Franco MC , Casarini DE , Carneiro‐Ramos MS , Sawaya AL , Barreto‐Chaves ML , Sesso R . Circulating renin‐angiotensin system and catecholamines in childhood: Is there a role for birthweight? Clin Sci (Lond) 114: 375‐380, 2008.
 59. Franco MC , Kawamoto EM , Gorjao R , Rastelli VM , Curi R , Scavone C , Sawaya AL , Fortes ZB , Sesso R . Biomarkers of oxidative stress and antioxidant status in children born small for gestational age: Evidence of lipid peroxidation. Pediatr Res 62: 204‐208, 2007.
 60. Gademan MG , van Eijsden M , Roseboom TJ , van der Post JA , Stronks K , Vrijkotte TG . Maternal prepregnancy body mass index and their children's blood pressure and resting cardiac autonomic balance at age 5 to 6 years. Hypertension 62: 641‐647, 2013. doi: 10.1161/HYPERTENSIONAHA.113.01511.
 61. Gaillard R , Steegers EA , Duijts L , Felix JF , Hofman A , Franco OH , Jaddoe VW . Childhood cardiometabolic outcomes of maternal obesity during pregnancy: The Generation R Study. Hypertension 63: 683‐691, 2014. doi: 10.1161/HYPERTENSIONAHA.113.02671.
 62. Gilbert JS , Lang AL , Grant AR , Nijland MJ . Maternal nutrient restriction in sheep: Hypertension and decreased nephron number in offspring at 9 months of age. J Physiol 565: 137‐147, 2005.
 63. Goldfarb DA , Martin SF , Braun WE , Schreiber MJ , Mastroianni B , Papajcik D , Rolin HA , Flecher S , Goormastic M , Novick AC . Renal outcomes 25 years after donor nephrectomy. J Urol. 166: 2043‐2047, 2001.
 64. Goyal R , Longo LD . Maternal protein deprivation: Sexually dimorphic programming of hypertension in the mouse. Hypertens Res 36: 29‐35, 2013. doi: 10.1038/hr.2012.129.
 65. Gray SP , Denton KM , Cullen‐McEwen L , Bertram JF , Moritz KM . Prenatal alcohol reduces nephron number and raises blood pressure in progeny. J Am Soc Npehrol 21: 1891‐1902, 2010. doi: 10.1681/ASN.2010040368.
 66. Gray SP , Kenna K , Bertram JF , Hoy WE , Yan EB , Bocking AD , Brien JF , Walker DW , Harding R , Moritz KM . Repeated ethanol exposure during late gestation decreases nephron endowment in fetal sheep. Am J Physiol Regul Integr Comp Physiol 295: R568‐R574, 2008. doi: 10.1152/ajpregu.90316.2008.
 67. Grigore D , Ojeda NB , Robertson EB , Dawson AS , Huffman CA , Bourassa EA , Speth RC , Brosnihan KB , Alexander BT . Placental insufficiency results in temporal alterations in the renin angiotensin system in male hypertensive growth restricted offspring. Am J Physiol Regul Integr Comp Physiol 293: R804‐R811, 2007.
 68. Guberman C , Jellyman JK , Han G , Ross MG , Desai M . Maternal high‐fat diet programs rat offspring hypertension and activates the adipose renin‐angiotensin system. Am J Obstet Gynecol 209: 262.e1‐8, 2013. doi: 10.1016/j.ajog.2013.05.023.
 69. Guimarães AM , Bettiol H , Souza LD , Gurgel RQ , Almeida ML , Ribeiro ER , Goldaniv MZ , Barbieri MA . Is adolescent pregnancy a risk factor for low birth weight? Rev Saude Publica 47: 11‐19, 2013.
 70. Guron G , Friberg P . An intact renin‐angiotensin system is a prerequisite for normal renal development. J Hypertens 18: 123‐137, 2000.
 71. Guzmán C , Cabrera R , Cárdenas M , Larrea F , Nathanielsz PW , Zambrano E . Protein restriction during fetal and neonatal development in the rat alters reproductive function and accelerates reproductive ageing in female progeny. J Physiol 572: 97‐108, 2006.
 72. Hadoke PW , Lindsay RS , Seckl JR , Walker BR , Kenyon CJ . Altered vascular contractility in adult female rats with hypertension programmed by prenatal glucocorticoid exposure. J Endocrinol 188: 435‐442, 2006.
 73. Hall JE , da Silva AA , do Carmo JM , Dubinion J , Hamza S , Munusamy S , Smith G , Stec DE . Obesity‐induced hypertension: Role of sympathetic nervous system, leptin, and melanocortins. J Biol Chem 285: 17271‐17276, 2010. doi: 10.1074/jbc.R110.113175.
 74. Harris A , Seckl J . Glucocorticoids, prenatal stress and the programming of disease. Horm Behav 59: 279‐89, 2011. doi: 10.1016/j.yhbeh.2010.06.007.
 75. Hayes DK , Feigal DW , Smith RA , Fuddy LJ . Maternal asthma, diabetes, and high blood pressure are associated with low birth weight and increased hospital birth and delivery charges; Hawai'i hospital discharge data 2003‐2008. Hawaii J Med Public Health 73: 49‐57, 2014.
 76. Hiraoka T , Kudo T , Kishimoto Y . Catecholamines in experimentally growth‐retarded rat fetus. Asia Oceania J Obstet Gynaecol 17: 341‐348, 1991.
 77. Hobbes FD . Reducing cardiovascular risk in diabetes: Beyond glycemic and blood pressure control. Int J Cardio 110: 137‐145, 2006.
 78. Holloway AC , Cuu DQ , Morrison KM , Gerstein HC , Tarnopolsky MA . Transgenerational effects of fetal and neonatal exposure to nicotine. Endocrine 31: 254‐259, 2007.
 79. Hughson M , Farris AB III , Douglas‐Denton R , Hoy WE , Bertram JF . Glomerular number and size in autopsy kidneys: The relationship to birth weight. Kidney Int 63: 2113‐2122, 2003.
 80. Innes KE , Byers TE , Marshall JA , Barón A , Orleans M , Hamman RF . Association of a woman's own birth weight with subsequent risk for gestational diabetes. JAMA 287: 2534‐2541, 2002.
 81. Innes KE , Marshall JA , Byers TE , Calonge N . A woman's own birth weight and gestational age predict her later risk of developing preeclampsia, a precursor of chronic disease. Epidemiology 10: 153‐160, 1999.
 82. Intapad S , Alexander BT . Pregnancy complications and later development of hypertension. Curr Cardiovasc Risk Rep 7: 183‐189, 2013.
 83. Intapad S , Ojeda NB , Dasinger JH , Alexander BT . Sex differences in the developmental origins of cardiovascular disease. Physiology (Bethesda) 29: 122‐132, 2014. doi: 10.1152/physiol.00045.2013.
 84. Intapad S , Tull FL , Brown AD , Dasinger JH , Ojeda NB , Fahling JM , Alexander BT . Renal denervation abolishes the age‐dependent increase in blood pressure in female intrauterine growth‐restricted rats at 12 months of age. Hypertension 61: 828‐834, 2013. doi: 10.1161/HYPERTENSIONAHA.111.00645.
 85. IJzerman RG , Stehouwer CD , de Geus EJ , van Weissenbruch MM , Delemarre‐van de Waal HA , Boomsma DI . Low birth weight is associated with increased sympathetic activity: Dependence on genetic factors. Circulation 108: 566‐571, 2003.
 86. Jansson T , Lambert GW . Effect of intrauterine growth restriction on blood pressure, glucose tolerance and sympathetic nervous system activity in the rat at 3‐4 months of age. J Hypertens 17: 1239‐1248, 1999.
 87. Jiang X , Ma H , Wang Y , Liu Y . Early life factors and type 2 diabetes. J Diabetes Res 2013: 485082, 2013. doi: 10.1155/2013/485082.
 88. Johnsson IW , Haglund B , Ahlsson F , Gustafsson J . A high birth weight is associated with increased risk of type 2 diabetes and obesity. Pediatr Obes 2014 [Epub ahead of print] PMID: 24916852 doi: 10.1111/ijpo.230.
 89. Jones BH , Standridge MK , Taylor JW , Moustaid N . Angiotensinogen gene expression in adipose tissue: Analysis of obese models and hormonal and nutritional control. Am J Physiol 273: R236‐R242, 1997.
 90. Jones CT , Robinson JS . Studies on experimental growth retardation in sheep. Plasma catecholamines in fetuses with small placenta. J Dev Physiol 5: 77‐87, 1983.
 91. Katkhuda R , Peterson ES , Roghair RD , Norris AW , Scholz TD , Segar JL . Sex‐specific programming of hypertension in offspring of late‐gestation diabetic rats. Pediatr Res 72: 352‐361, 2012. doi: 10.1038/pr.2012.93.
 92. Kandasamy Y , Smith R , Wright IM , Lumbers ER . Extra‐uterine growth in preterm infants: Oligonephropathy and prematurity. Pediatr Nephrol 28: 1971‐1796, 2013. doi: 10.1007/s00467‐013‐2462‐3.
 93. Kawamura M , Itoh H , Yura S , Mogami H , Fujii T , Makino H , Miyamoto Y , Yoshimasa Y , Aoe S , Ogawa Y , Sagawa N , Kanayama N , Konishi I . Isocaloric high‐protein diet ameliorates systolic blood pressure increase and cardiac remodeling caused by maternal caloric restriction in adult mouse offspring. Endocr J 56: 679‐689, 2009.
 94. Kelstrup L , Damm P , Mathiesen ER , Hansen T , Vaag AA , Pedersen O , Clausen TD . Insulin resistance and impaired pancreatic β‐cell function in adult offspring of women with diabetes in pregnancy. J Clin Endocrinol Metab 98: 3793‐313801, 2013. doi: 10.1210/jc.2013‐1536.
 95. Khan IY , Taylor PD , Dekou V , Seed PT , Lakasing L , Graham D , Dominiczak AF , Hanson MA , Poston L . Gender‐linked hypertension in offspring of lard‐fed pregnant rats. Hypertension 41: 168‐175, 2003.
 96. Ko TJ , Tsai LY , Chu LC , Yeh SJ , Leung C , Chen CY , Chou HC , Tsao PN , Chen PC , Hsieh WS . Parental smoking during pregnancy and its association with low birth weight, small for gestational age, and preterm birth offspring: A birth cohort study. Pediatr Neonatol 55: 20‐27, 2014. doi: 10.1016/j.pedneo.2013.05.005.
 97. Kramer MS . The epidemiology of low birthweight. Nestle Nutr Inst Workshop Ser 74: 1‐10, 2013. doi: 10.1159/000348382.
 98. Lackland DT , Bendall HE , Osmond C , Egan BM , Barker DJ . Low birth weights contribute to high rates of early‐onset chronic renal failure in the Southeastern United States. Arch Intern Med 160: 1472‐1476, 2000.
 99. Lackland DT , Egan BM , Syddall HE , Barker DJ . Associations between birth weight and antihypertensive medication in black and white medicaid recipients. Hypertension 39: 179‐183, 2002.
 100. LaMarca B , Cornelius D , Wallace K . Elucidating immune mechanisms causing hypertension during pregnancy. Physiology (Bethesda) 28: 225‐233, 2013. doi: 10.1152/physiol.00006.2013.
 101. Langley‐Evans SC . Hypertension induced by foetal exposure to a maternal low‐protein diet, in the rat, is prevented by pharmacological blockade of maternal glucocorticoid synthesis. J Hypertens 15: 537‐544, 1997.
 102. Langley‐Evans SC , Phillips GJ , Benediktsson R , Gardner DS , Edwards CR , Jackson AA , Seckl JR . Protein intake in pregnancy, placental glucocorticoid metabolism and the programming of hypertension in the rat. Placenta 17: 169‐172, 1996.
 103. Langley‐Evans SC , Phillips GJ , Jackson AA . In utero exposure to maternal low protein diets induces hypertension in weanling rats, independently of maternal blood pressure changes. Clin Nutr 13: 319‐324, 1994.
 104. Law CM , Shiell AW . Is blood pressure inversely related to birth weight? The strength of evidence from a systematic review of the literature. J Hypertens 14: 935‐941, 1996.
 105. Law CM , Shiell AW , Newsome CA , Syddall HE , Shinebourne EA , Fayers PM , Martyn CN , de Swiet M . Fetal, infant, and childhood growth and adult blood pressure: A longitudinal study from birth to 22 years of age. Circulation 105: 1088‐1092, 2002.
 106. Lawlor DA , Davey Smith G , Ebrahim S . Birth weight is inversely associated with coronary heart disease in post‐menopausal women: Findings from the British women's heart and health study. J Epidemiol Community Health 58: 120‐125, 2004.
 107. Lawlor DA , Ebrahim S , Davey Smith G . Is there a sex difference in the association between birth weight and systolic blood pressure in later life? Findings from a meta‐regression analysis. Am J Epidemiol 156: 1100‐1104, 2002.
 108. Lazdam M , de la Horra A , Pitcher A , Mannie Z , Diesch J , Trevitt C , Kylintireas I , Contractor H , Singhal A , Lucas A , Neubauer S , Kharbanda R , Alp N , Kelly B , Leeson P . Elevated blood pressure in offspring born premature to hypertensive pregnancy: Is endothelial dysfunction the underlying vascular mechanism? Hypertension 56: 159‐165, 2010. doi: 10.1161/HYPERTENSIONAHA.110.150235.
 109. Leeson CP , Kattenhorn M , Morley R , Lucas A , Deanfield JE . Impact of low birth weight and cardiovascular risk factors on endothelial function in early adult life. Circulation 103: 1264‐1268, 2001.
 110. Lesage J , Sebaai N , Leonhardt M , Dutriez‐Casteloot I , Breton C , Deloof S , Vieau D . Perinatal maternal undernutrition programs the offspring hypothalamo‐pituitary‐adrenal (HPA) axis. Stress 9: 183‐981, 2006.
 111. Lindsay RS , Lindsay RM , Edwards CR , Seckl JR . Inhibition of 11‐beta‐hydroxysteroid dehydrogenase in pregnant rats and the programming of blood pressure in the offspring. Hypertension 27: 1200‐1204, 1996.
 112. Liu XM , Kong J , Song WW , Lu Y . Glucose metabolic and gluconeogenic pathways disturbance in the intrauterine growth restricted adult male rats. Chin Med Sci J 24: 208‐212, 2009.
 113. Longo LD , Pearce WJ . Fetal cerebrovascular acclimatization responses to high‐altitude, long‐term hypoxia: A model for prenatal programming of adult disease? Am J Physiol Regul Integr Comp Physiol 288: R16‐R24, 2005.
 114. Loria AS , D'Angelo G , Pollock DM , Pollock JS . Early life stress downregulates endothelin receptor expression and enhances acute stress‐mediated blood pressure responses in adult rats. Am J Physiol Regul Integr Comp Physiol 299: R185‐R191, 2010. doi: 10.1152/ajpregu.00333.2009.
 115. Loria AS , Ho DH , Pollock JS . A mechanistic look at the effects of adversity early in life on cardiovascular disease risk during adulthood. Acta Physiol (Oxf) [Epub ahead of print] 2013. doi: 10.1111/apha.12189 PMID: 2433084.
 116. Loria AS , Pollock DM , Pollock JS . Early life stress sensitizes rats to angiotensin II‐induced hypertension and vascular inflammation in adult life. Hypertension 55: 494‐499, 2010. doi: 10.1161/HYPERTENSIONAHA.109.145391.
 117. Loria A , Reverte V , Salazar F , Saez F , Llinas MT , Salazar FJ . Changes in renal hemodynamics and excretory function induced by a reduction of ANG II effects during renal development. Am J Physiol Regul Integr Comp Physiol 293: R695‐R700, 2007.
 118. Loria AS , Yamamoto T , Pollock DM , Pollock JS . Early life stress induces renal dysfunction in adult male rats but not female rats. Am J Physiol Regul Integr Comp Physiol 304: R121‐R129, 2013. doi: 10.1152/ajpregu.00364.2012.
 119. Lurbe E , Garcia‐Vicent C , Torro MI , Aguilar F , Redon J . Associations of birth weight and postnatal weight gain with cardiometabolic risk parameters at 5 years of age. Hypertension 63: 1326‐1332, 2014. doi: 10.1161/HYPERTENSIONAHA.114.03137.
 120. Ma N , Nicholson CJ , Wong M , Holloway AC , Hardy DB . Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase. Toxicol Appl Pharmacol 275: 1‐11, 2014. doi: 10.1016/j.taap.2013.12.010.
 121. Maccari S , Darnaudery M , Morley‐Fletcher S , Zuena AR , Cinque C , Van Reeth O . Prenatal stress and long‐term consequences: Implications of glucocorticoid hormones. Neurosci Biobehav Rev 27: 119‐127, 2003.
 122. Malti N , Merzouk H , Merzouk SA , Loukidi B , Karaouzene N , Malti A , Narce M . Oxidative stress and maternal obesity: Feto‐placental unit interaction. Placenta 35: 411‐416, 2014. doi: 10.1016/j.placenta.2014.03.010.
 123. Manning J , Vehaskari VM . Low birth weight‐associated adult hypertension in the rat. Pediatr Nephrol 16: 417‐422, 2001.
 124. Mao C , Zhang H , Xiao D , Zhu L , Ding Y , Zhang Y , Wu L , Xu Z , Zhang L . Perinatal nicotine exposure alters AT 1 and AT 2 receptor expression pattern in the brain of fetal and offspring rats. Brain Res 1243: 47‐52, 2008. doi: 10.1016/j.brainres.2008.09.060.
 125. Mamun AA , Kinarivala MK , O'Callaghan M , Williams G , Najman J , Callaway L . Does hypertensive disorder of pregnancy predict offspring blood pressure at 21 years? Evidence from a birth cohort study. J Hum Hypertens 26: 288‐294, 2012. doi: 10.1038/jhh.2011.35.
 126. Mamun AA , O'Callaghan M , Callaway L , Williams G , Najman J , Lawlor DA . Associations of gestational weight gain with offspring body mass index and blood pressure at 21 years of age: Evidence from a birth cohort study. Circulation 119: 1720‐1727, 2009. doi: 10.1161/CIRCULATIONAHA.108.813436.
 127. Marshall NE , Guild C , Cheng YW , Caughey AB , Halloran DR . Racial disparities in pregnancy outcomes in obese women. J Matern Fetal Neonatal Med 27: 122‐126, 2014. doi: 10.3109/14767058.2013.806478.
 128. Martínez D , Pentinat T , Ribó S , Daviaud C , Bloks VW , Cebrià J , Villalmanzo N , Kalko SG , Ramón‐Krauel M , Díaz R , Plösch T , Tost J , Jiménez‐Chillarón JC . In utero undernutrition in male mice programs liver lipid metabolism in the second‐generation offspring involving altered lxra DNA methylation. Cell Metab 3;19: 941‐951, 2014. doi: 10.1016/j.cmet.2014.03.026.
 129. Martinez‐Aguayo A , Aglony M , Bancalari R , Avalos C , Bolte L , Garcia H , Loureiro C , Carvajal C , Campino C , Inostroza A , Fardella C . Birth weight is inversely associated with blood pressure and serum aldosterone and cortisol levels in children. Clin Endocrinol (Oxf) 76: 713‐718, 2012. doi: 10.1111/j.1365‐2265.2011.04308.x.
 130. Mission JF , Marshall NE , Caughey AB . Obesity in pregnancy: A big problem and getting bigger. Obstet Gynecol Surv 68: 389‐399, 2013. doi: 10.1097/OGX.0b013e31828738ce.
 131. Moritz KM , Cuffe JS , Wilson LB , Dickinson H , Wlodek ME , Simmons DG , Denton KM . Review: Sex specific programming: A critical role for the renal renin‐angiotensin system. Placenta 31: S40‐S46, 2010. doi: 10.1016/j.placenta.2010.01.006.
 132. Moritz KM , Mazzuca MQ , Siebel AL , Mibus A , Arena D , Tare M , Owens JA , Wlodek ME . Uteroplacental insufficiency causes a nephron deficit, modest renal insufficiency but no hypertension with ageing in female rats. J Physiol 587: 2635‐2646, 2009. doi: 10.1113/jphysiol.2009.170407.
 133. Moritz KM , Wintour EM , Dodic M . Fetal uninephrectomy leads to postnatal hypertension and compromised renal function. Hypertension 39: 1071‐1076, 2002.
 134. Morton JS , Rueda‐Clausen CF , Davidge ST . Flow‐mediated vasodilation is impaired in adult rat offspring exposed to prenatal hypoxia. J Appl Physiol (1985) 110: 1073‐1082, 2011. doi: 10.1152/japplphysiol.01174.2010.
 135. Mossa F , Carter F , Walsh SW , Kenny DA , Smith GW , Ireland JL , Hildebrandt TB , Lonergan P , Ireland JJ , Evans AC . Maternal undernutrition in cows impairs ovarian and cardiovascular systems in their offspring. Biol Reprod 88: 92, 2013. doi: 10.1095/biolreprod.112.107235.
 136. Murray AJ . Oxygen delivery and fetal‐placental growth: Beyond a question of supply and demand? Placenta 33: e16‐e22, 2012. doi: 10.1016/j.placenta.2012.06.006.
 137. Myrie SB , MacKay DS , Van Vliet BN , Bertolo RF . Early programming of adult blood pressure in the low birth weight Yucatan miniature pig is exacerbated by a post‐weaning high‐salt‐fat‐sugar diet. Br J Nutr 108: 1218‐1225, 2012.
 138. Narkun‐Burgess DM , Nolan CR , Norman JE , Page WF , Miller PL , Meyer TW . Forty‐five year follow‐up after uninephrectomy. Kidney Int 43: 1110‐1115, 1993.
 139.National Center for Health Statistics, final natality data. Retrieved February 4th, 2004, from www.marchofdimes.com/peristats.
 140. Nehiri T , Duong Van Huyen JP , Viltard M , Fassot C , Heudes D , Freund N , Deschênes G , Houillier P , Bruneval P , Lelièvre‐Pégorier M . Exposure to maternal diabetes induces salt‐sensitive hypertension and impairs renal function in adult rat offspring. Diabetes 57: 2167‐2175, 2008. doi: 10.2337/db07‐0780.
 141. Nykjaer C , Alwan NA , Greenwood DC , Simpson NA , Hay AW , White KL , Cade JE . Maternal alcohol intake prior to and during pregnancy and risk of adverse birth outcomes: Evidence from a British cohort. J Epidemiol Community Health 68: 542‐549, 2014. doi: 10.1136/jech‐2013‐202934.
 142. Øglaend B , Forman MR , Romundstad PR , Nilsen ST , Vatten LJ . Blood pressure in early adolescence in the offspring of preeclamptic and normotensive pregnancies. J Hypertens 27: 2051‐2054, 2009. doi: 10.1097/HJH.0b013e328330052a.
 143. Ojeda NB . Low birth weight increases susceptibility to renal injury in a rat model of mild ischemia‐reperfusion. Am J Physiol Renal Physiol 301: F420‐F426, 2011. doi: 10.1152/ajprenal.00045.2011.
 144. Ojeda NB , Grigore D , Robertson EB , Alexander BT . Estrogen protects against increased blood pressure in postpubertal female growth restricted offspring. Hypertension 50: 679‐685, 2007.
 145. Ojeda NB , Grigore D , Yanes LL , Iliescu R , Robertson EB , Zhang H , Alexander BT . Testosterone contributes to marked elevations in mean arterial pressure in adult male intrauterine growth restricted offspring. Am J Physiol Regul Integr Comp Physiol 292: R758‐763, 2007.
 146. Ojeda NB , Hennington BS , Williamson DT , Hill ML , Betson NE , Sartori‐Valinotti JC , Reckelhoff JF , Royals TP , Alexander BT . Oxidative stress contributes to sex differences in blood pressure in adult growth‐restricted offspring. Hypertension 60: 114‐122, 2012. doi: 10.1161/HYPERTENSIONAHA.112.192955.
 147. Ojeda NB , Intapad S , Royals TP , Black JT , Dasinger JH , Tull FL , Alexander BT . Hypersensitivity to acute ANG II in female growth‐restricted offspring is exacerbated by ovariectomy. Am J Physiol Regul Integr Comp Physiol 301: R1199‐R1205, 2011. doi: 10.1152/ajpregu.00219.2011.
 148. Ojeda NB , Johnson WR , Dwyer TM , Alexander BT . Early renal denervation prevents development of hypertension in growth‐restricted offspring. Clin Exp Pharmacol Physiol 34: 1212‐1216, 2007.
 149. Ojeda NB , Royals TP , Black JT , Dasinger JH , Johnson JM , Alexander BT . Enhanced sensitivity to acute angiotensin II is testosterone dependent in adult male growth‐restricted offspring. Am J Physiol Regul Integr Comp Physiol 298: R1421‐R1427, 2010. doi: 10.1152/ajpregu.00096.2010.
 150. Ortiz LA , Quan A , Weinberg A , Baum M . Effect of prenatal dexamethasone on rat renal development. Kidney Int 59: 1663‐1669, 2001.
 151. Ortiz LA , Quan A , Zarzar F , Weinberg A , Baum M . Prenatal dexamethasone programs hypertension and renal injury in the rat. Hypertension 41: 328‐334, 2003.
 152. Ozaki T , Nishina H , Hanson MA , Poston L . Dietary restriction in pregnant rats causes gender‐related hypertension and vascular dysfunction in offspring. J Physiol 530: 141‐152, 2001.
 153. Palei AC , Spradley FT , Warrington JP , George EM , Granger JP . Pathophysiology of hypertension in pre‐eclampsia: A lesson in integrative physiology. ActaPhysiol (Oxf) 208: 224‐233, 2013. doi: 10.1111/apha.12106.
 154. Page KA , Romero A , Buchanan TA , Xiang A . Gestational diabetes mellitus, maternal obesity, and adiposity in offspring. J Pediatr 164: 807‐810, 2014. doi: 10.1016/j.jpeds.2013.11.063.
 155. Payne JA , Alexander BT , Khalil RA . Reduced endothelial vascular relaxation in growth‐restricted offspring of pregnant rats with reduced uterine perfusion. Hypertension 42: 768‐774, 2003.
 156. Petry CJ , Dorling MW , Wang CL , Pawlak DB , Ozanne SE . Catecholamine levels and receptor expression in low protein rat offspring. Diabet Med 17: 848‐853, 2000.
 157. Pham TD , MacLennan NK , Chiu CT , Laksana GS , Hsu JL , Lane RH . Uteroplacental insufficiency increases apoptosis and alters p53 gene methylation in the full‐term IUGR rat kidney. Am J Physiol Regul Integr Comp Physiol 285: R962‐R970, 2003.
 158. Pinheiro AR , Salvucci ID , Augila MB , Mandarim‐de‐Lacerda CA . Protein restriction during gestation and/or lactation causes adverse transgenerational effects on biometry and glucose metabolism in F1 and F2 progenies of rats. Clin Sci (London) 114: 381‐392, 2008.
 159. Pirkola J , Pouta A , Bloigu A , Hartikainen AL , Laitinen J , Järvelin MR , Vääräsmäki M . Risks of overweight and abdominal obesity at age 16 years associated with prenatal exposures to maternal prepregnancy overweight and gestational diabetes mellitus. Diabetes Care 33: 1115‐1121, 2010. doi: 10.2337/dc09‐1871.
 160. Pladys P , Lahaie I , Cambonie G , Thibault G , Lê NL , Abran D , Nuyt AM . Role of brain and peripheral angiotensin II in hypertension and altered arterial baroreflex programmed during fetal life in rat. Pediatr Res 55: 1042‐1049, 2004.
 161. Ponzio BF , Carvalho MH , Fortes ZB , do Carmo Franco M . Implications of maternal nutrient restriction in transgenerational programming of hypertension and endothelial dysfunction across F1‐F3 offspring. Life Sci 90: 571‐577, 2012. doi: 10.1016/j.lfs.2012.01.017.
 162. Prior LJ , Davern PJ , Burke SL , Lim K , Armitage JA , Head GA . Exposure to a high‐fat diet during development alters leptin and ghrelin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits. Hypertension 63: 338‐345, 2014. doi: 10.1161/HYPERTENSIONAHA.113.02498.
 163. Quan A , Baum M . Renal nerve stimulation augments effect of intraluminal angiotensin II on proximal tubule transport. Am J Physiol Renal Physiol 282: F1043‐F1048, 2002.
 164. Racasan S , Braam B , van der Giezen DM , Goldschmeding R , Boer P , Koomans HA , Joles JA . Perinatal L‐arginine and antioxidant supplements reduce adult blood pressure in spontaneously hypertensive rats. Hypertension 44: 83‐88, 2004.
 165. Reinisch JM , Simon NG , Karwo WG , Gandelman R . Prenatal exposure to prednisone in humans and animals retards intra‐uterine growth. Science 202: 436‐438, 1978.
 166. Reverte V , Tapia A , Baile G , Gambini J , Gíménez I , Llinas MT , Salazar FJ . Role of angiotensin II in arterial pressure and renal hemodynamics in rats with altered renal development: Age‐ and sex‐dependent differences. Am J Physiol Renal Physiol 304: F33‐F40, 2013. doi: 10.1152/ajprenal.00424.2012.
 167. Reverte V , Tapia A , Loria A , Salazar F , Llinas MT , Salazar FJ . COX2 inhibition during nephrogenic period induces ANG II hypertension and sex‐dependent changes in renal function during aging. Am J Physiol Renal Physiol 306: F534‐F541, 2014. doi: 10.1152/ajprenal.00535.2013.
 168. Ribeiro MM , Trombetta IC , Batalha LT , Rondon MU , Forjaz CL , Barretto AC , Villares SM , Negrão CE . Muscle sympathetic nerve activity and hemodynamic alterations in middle‐aged obese women. Braz J Med Biol Res 34: 475‐478, 2001.
 169. Rich‐Edwards JW , Colditz GA , Stampfer MJ , Willett WC , Gillman MW , Hennekens CH , Speizer FE , Manson JE . Birthweight and the risk for type 2 diabetes mellitus in adult women. Ann Intern Med 130: 278‐284, 1999.
 170. Roberts JM , Gammill HS . Preeclampsia. Hypertension 46: 1246‐1249, 2005.
 171. Rocha SO , Gomes GN , Forti AL , do CarmoPinho Franco M , Fortes ZB , de FátimaCavanal M , Gil FZ . Long‐term effects of maternal diabetes on vascular reactivity and renal function in rat male offspring. Pediatr Res 58: 1274‐1279, 2005.
 172. Roseboom TJ , van der Meulen JH , Osmond C , Barker DJ , Ravelli AC , Bleker OP . Plasma lipid profiles in adults after prenatal exposure to the Dutch famine. Am J Clin Nutr 72: 1101‐1106, 2000.
 173. Roseboom TJ , van der Meulen JH , Osmond C , Barker DJ , Ravelli AC , Schroeder‐Tanka JM , van Montfrans GA , Michels RP , Bleker OP . Coronary heart disease after prenatal exposure to the Dutch famine, 1944‐45. Heart 84: 595‐598, 2000.
 174. Rueda‐Clausen CF , Morton JS , Davidge ST . Effects of hypoxia‐induced intrauterine growth restriction on cardiopulmonary structure and function during adulthood. Cardiovasc Res 81: 713‐722, 2009. doi: 10.1093/cvr/cvn341.
 175. Rueda‐Clausen CF , Morton JS , Dolinsky VW , Dyck JR , Davidge ST . Synergistic effects of prenatal hypoxia and postnatal high‐fat diet in the development of cardiovascular pathology in young rats. Am J Physiol Regul Integr Comp Physiol 303: R418‐R426, 2012. doi: 10.1152/ajpregu.00148.2012.
 176. Rueda‐Clausen CF , Morton JS , Lopaschuk GD , Davidge ST . Long‐term effects of intrauterine growth restriction on cardiac metabolism and susceptibility to ischaemia/reperfusion. Cardiovasc Res 90: 285‐294, 2011. doi: 10.1093/cvr/cvq363.
 177. Samuelsson AM , Alexanderson C , Mölne J , Haraldsson B , Hansell P , Holmäng A . Prenatal exposure to interleukin‐6 results in hypertension and alterations in the renin‐angiotensin system of the rat. J Physiol 575: 855‐867, 2006.
 178. Samuelsson AM , Matthews PA , Argenton M , Christie MR , McConnell JM , Jansen EH , Piersma AH , Ozanne SE , Twinn DF , Remacle C , Rowlerson A , Poston L , Taylor PD . Diet‐induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: A novel murine model of developmental programming. Hypertension 51: 383‐392, 2008.
 179. Samuelsson AM , Matthews PA , Jansen E , Taylor PD , Poston L . Sucrose feeding in mouse pregnancy leads to hypertension, and sex‐linked obesity and insulin resistance in female offspring. Front Physiol 4: 14, 2013. doi: 10.3389/fphys.2013.00014.
 180. Samuelsson AM , Morris A , Igosheva N , Kirk SL , Pombo JM , Coen CW , Poston L , Taylor PD . Evidence for sympathetic origins of hypertension in juvenile offspring of obese rats. Hypertension 55: 76‐82, 2010. doi: 10.1161/HYPERTENSIONAHA.109.139402.
 181. Sandboge S , Moltchanova E , Blomstedt PA , Salonen MK , Kajantie E , Osmond C , Barker DJ , Eriksson JG . Birth‐weight and resting metabolic rate in adulthood ‐ sex‐specific differences. Ann Med 44: 296‐303, 2012. doi: 10.3109/07853890.2010.549147.
 182. Sapre S , Thakur R . Lifestyle and dietary factors that determine age at menopause. J Midlife Health 5:3‐5, 2014. doi: 10.4103/0976‐7800.127779.
 183. Saran R , Marshall S , Madsen R , Keavey P . Tapson JS. Long‐term follow‐up of kidney donors: A longitudinal study. Nephrol Dial Transplant 12: 1615‐1621, 1997.
 184. Saxena AR , Karumanchi SA , Brown NJ , Royle CM , McElrath TF , Seely EW . Increased sensitivity to angiotensin II is present postpartum in women with a history of hypertensive pregnancy. Hypertension 55: 1239‐1245, 2010. doi: 10.1161/HYPERTENSIONAHA.109.147595.
 185. Schoof E , Girstl M , Frobenius W , Kirschbaum M , Dörr HG , Rascher W , Dötsch J . Decreased gene expression of 11beta‐hydroxysteroid dehydrogenase type 2 and 15‐hydroxyprostaglandin dehydrogenase in human placenta of patients with preeclampsia. J Clin Endocrinol Metab 86: 1313‐1317, 2001.
 186. Seghieri G , Anichini R , De Bellis A , Alviggi L , Franconi F , Breschi MC . Relationship between gestational diabetes mellitus and low maternal birth weight. Diabetes Care 25: 1761‐1765, 2002.
 187. Selak MA , Storey BT , Peterside I , Simmons RA . Impaired oxidative phosphorylation in skeletal muscle of intrauterine growth‐retarded rats. Am J Physiol Endocrinol Metab 285: E130‐E137, 2003.
 188. Sen S , Simmons RA . Maternal antioxidant supplementation prevents adiposity in the offspring of Western diet‐fed rats. Diabetes 59: 3058‐3065, 2010. doi: 10.2337/db10‐0301.
 189. Seng JS , Low LK , Sperlich M , Ronis DL , Liberzon I . Post‐traumatic stress disorder, child abuse history, birthweight and gestational age: A prospective cohort study. BJOG 118: 1329‐1339, 2011. doi: 10.1111/j.1471‐0528.2011.03071.x.
 190. Sherman RC , Langley‐Evans SC . Early administration of angiotensin‐converting enzyme inhibitor captopril, prevents the development of hypertension programmed by intrauterine exposure to a maternal low‐protein diet in the rat. Clin Sci (Lond) 94: 373‐381, 1998.
 191. Simonetti GD , Schwertz R , Klett M , Hoffmann GF , Schaefer F , Wühl E . Determinants of blood pressure in preschool children: The role of parental smoking. Circulation 123: 292‐298, 2011. doi: 10.1161/CIRCULATIONAHA.110.958769.
 192. Singh RR , Cullen‐McEwen LA , Kett MM , Boon WM , Dowling J , Bertram JF , Moritz KM . Prenatal corticosterone exposure results in altered AT1/AT2, nephron deficit and hypertension in the rat offspring. J Physiol 579: 503‐513, 2007.
 193. Singhal A , Cole TJ , Fewtrell M , Kennedy K , Stephenson T , Elias‐Jones A , Lucas A . Promotion of faster weight gain in infants born small for gestational age: Is there an adverse effect on later blood pressure? Circulation 115: 213‐220, 2007.
 194. Slater‐Jefferies JL , Lillycrop KA , Townsend PA , Torrens C , Hoile SP , Hanson MA , Burdge GC . Feeding a protein‐restricted diet during pregnancy induces altered epigenetic regulation of peroxisomal proliferator‐activated receptor‐α in the heart of the offspring. J Dev Orig Health Dis 2: 250‐255, 2011. doi: 10.1017/S2040174410000425.
 195. Spencer SJ , Tilbrook A . Neonatal overfeeding alters adult anxiety and stress responsiveness. Psychoneuroendocrinology 34: 1133‐1143, 2009. doi: 10.1016/j.psyneuen.2009.02.013.
 196. Spracklen CN , Ryckman KK , Harland KK , Saftlas AF . Effects of smoking and preeclampsia on birthweight for gestational age. J Matern Fetal Neonatal Med 4: 1‐20, 2014.
 197. Stein AD , Zybert PA , van de Bor M , Lumey LH . Intrauterine famine exposure and body proportions at birth: The Dutch Hunger Winter. Int J Epidemiol 33: 831‐836, 2004.
 198. Steiner AZ , D'Aloisio AA , DeRoo LA , Sandler DP , Baird DD . Association of intrauterine and early‐life exposures with age at menopause in the Sister Study. Am J Epidemiol 172: 140‐148, 2010.
 199. Stewart T , Jung FF , Manning J , Vehaskari VM . Kidney immune cell infiltration and oxidative stress contribute to prenatally programmed hypertension. Kidney Int 68: 2180‐2188, 2005.
 200. Stoffers DA , Desai BM , DeLeon DD , Simmons RA . Neonatal exendin‐4 prevents the development of diabetes in the intrauterine growth‐retarded rat. Diabetes 52: 734‐740, 2003.
 201. Strutz KL , Hogan VK , Siega‐Riz AM , Suchindran CM , Halpern CT , Hussey JM . Preconception stress, birth weight, and birth weight disparities among US women. Am J Public Health 12: e1‐e8, 2014.
 202. Strutz KL , Richardson LJ , Hussey JM . Selected preconception health indicators and birth weight disparities in a national study. Womens Health Issues 24: e89‐e97, 2014. doi: 10.1016/j.whi.2013.10.001.
 203. Styrud J , Eriksson UJ , Grill V , Swenne I . Experimental intrauterine growth retardation in the rat causes a reduction of pancreatic B‐cell mass, which persists into adulthood. Biol Neonate 88: 122‐128, 2005.
 204. Szpera‐Gozdziewicz A , Breborowicz GH . Endothelial dysfunction in the pathogenesis of pre‐eclampsia. Front Biosci (Landmark Ed) 19: 734‐746, 2014.
 205. Tallam LS , da Silva AA , Hall JE . Melanocortin‐4 receptor mediates chronic cardiovascular and metabolic actions of leptin. Hypertension 48: 58‐64, 2006.
 206. Tan EK , Tan EL . Alterations in physiology and anatomy during pregnancy. Best Pract Res Clin Obstet Gynaecol 27: 791‐802, 2013. doi: 10.1016/j.bpobgyn.2013.08.001.
 207. Tao H , Rui C , Zheng J , Tang J , Wu L , Shi A , Chen N , He R , Wu C , Li J , Yin X , Zhang P , Zhu Z , Tao J , Xiao J , Mao C , Xu Z . Angiotensin II‐mediated vascular changes in aged offspring rats exposed to perinatal nicotine. Peptides 44: 111‐119, 2013. doi: 10.1016/j.peptides.2013.02.019.
 208. Tare M , Parkington HC , Bubb KJ , Wlodek ME . Uteroplacental insufficiency and lactational environment separately influence arterial stiffness and vascular function in adult male rats. Hypertension 60: 378‐386, 2012. doi: 10.1161/HYPERTENSIONAHA.112.190876.
 209. Thamotharan M , Garg M , Oak S , Rogers LM , Pan G , Sangiorgi F , Lee PW , Devaskar SU . Transgenerational inheritance of the insulin‐resistant phenotype in embryo‐transferred intrauterine growth‐restricted adult female rat offspring. Am J Physiol Endocrinol Metab 292: E1270‐E1279, 2007.
 210. Thamotharan M , McKnight RA , Thamotharan S , Kao DJ , Devaskar SU . Aberrant insulin‐induced GLUT4 translocation predicts glucose intolerance in the offspring of a diabetic mother. Am J Physiol Endocrinol Metab 284: E901‐E914, 2003.
 211. Thamotharan M , Shin BC , Suddirikku DT , Thamotharan S , Garg M , Devaskar SU . GLUT4 expression and subcellular localization in the intrauterine growth restricted adult rat female offspring. Am J Physiol Endocrinol Metab 288: E935‐947, 2005.
 212. Theys N , Bouckenooghe T , Ahn MT , Remacle C , Reusens B . Maternal low‐protein diet alters pancreatic islet mitochondrial function in a sex‐specific manner in the adult rat. Am J Physiol Regul Integr Comp Physiol 297: R1516‐R1525, 2009. doi: 10.1152/ajpregu.00280.2009.
 213. Thompson ML , Ananth CV , Jaddoe VW , Miller RS , Williams MA . The association of maternal adult weight trajectory with preeclampsia and gestational diabetes mellitus. Paediatr Perinat Epidemiol 28: 287‐296, 2014. doi: 10.1111/ppe.12128.
 214. Thorn SR , REgnault TR , Brown LD , Rozance PJ , Keng J , Roper M , Wilkening RB , Hay WW Jr , Friedman JE . Intrauterine growth restriction increases fetal hepatic gluconeogenic capacity and reduces messenger ribonucleic acid translation initiation and nutrient sensing in fetal liver and skeletal muscle. Endocrinology 150: 3021‐3030, 2009. doi: 10.1210/en.2008‐1789.
 215. Tom SE , Cooper R , Kuh D , Guralnik JM , Hardy R , Power C . Fetal environment and early age at natural menopause in a British birth cohort study. Hum Reprod 25: 791‐798, 2010. doi: 10.1093/humrep/dep451.
 216. Torrens C , Hanson MA , Gluckman PD , Vickers MH . Maternal undernutrition leads to endothelial dysfunction in adult male rat offspring independent of postnatal diet. Br J Nutr 101: 27‐33, 2009. doi: 10.1017/S0007114508988760.
 217. Tsadok MA , Friedlander Y , Paltiel O , Manor O , Meiner V , Hochner H , Sagy Y , Sharon N , Yazdgerdi S , Siscovick D , Elchalal U . Obesity and blood pressure in 17‐year‐old offspring of mothers with gestational diabetes: Insights from the Jerusalem Perinatal Study. Exp Diabetes Res 2011: 906154, 2011. doi: 10.1155/2011/906154.
 218. van Abeelen AF , de Rooij SR , Osmond C , Painter RC , Veenendaal MV , Bossuyt PM , Elias SG , Grobbee DE , van der Schouw YT , Barker DJ , Roseboom TJ . The sex‐specific effects of famine on the association between placental size and later hypertension. Placenta 32: 694‐698, 2011. doi: 10.1016/j.placenta.2011.06.012.
 219. van Eijsden M , Vrijkotte TG , Gemke RJ , van der Wal MF . Cohort profile: The Amsterdam Born Children and their Development (ABCD) study. Int J Epidemiol 40: 1176‐1186, 2011. doi: 10.1093/ije/dyq128.
 220. van Straten EM , Bloks VW , Huijkman NC , Baller JF , van Meer H , Lütjohann D , Kuipers F , Plösch T . The liver X‐receptor gene promoter is hypermethylated in a mouse model of prenatal protein restriction. Am J Physiol Regul Integr Comp Physiol 298: R275‐R282, 2010. doi: 10.1152/ajpregu.00413.2009.
 221. Vatten LJ , Romundstad PR , Holmen TL , Hsieh CC , Trichopoulos D , Stuver SO . Intrauterine exposure to preeclampsia and adolescent blood pressure, body size, and age at menarche in female offspring. Obstet Gynecol 101: 529‐533, 2003.
 222. Vickers MH . Early life nutrition, epigenetics and programming of later life disease. Nutrients 6: 2165‐2178, 2014. doi: 10.3390/nu6062165.
 223. Vos LE , Oren A , Bots ML , Gorissen WH , Grobbee DE , Uiterwaal CS . Birth size and coronary heart disease risk score in young adulthood. The Atherosclerosis Risk in Young Adults (ARYA) study. Eur J Epidemiol 21: 33‐38, 2006.
 224. Vuquin P , Raab E , Liu B , Barzilai N , Simmons R . Hepatic insulin reistance precedes the development of diabetes in a model of intrauterine growth restriction. Diabetes 53: 2617‐2622, 2004.
 225. Wahabi HA , Fayed AA , Alzeidan RA , Mandil AA . The independent effects of maternal obesity and gestational diabetes on the pregnancy outcomes. BMC Endocr Disord 14: 47, 2014. doi: 10.1186/1472‐6823‐14‐47.
 226. Wang X , Poole JC , Treiber FA , Harshfield GA , Hanevold CD , Snieder H . Ethnic and gender differences in ambulatory blood pressure trajectories: Results from a 15‐year longitudinal study in youth and young adults. Circulation 114: 2780‐2787, 2006.
 227. Washburn LK , Brosnihan KB , Chappell MC , Diz DI , Gwathmey TM , Nixon PA , Russell GB , Snively BM , O'Shea TM . The renin‐angiotensin‐aldosterone system in adolescent offspring born prematurely to mothers with preeclampsia. J Renin Angiotensin Aldosterone Syst 2014 [Epub ahead of print]. PMID: 24737639
 228. Washburn L , Nixon P , Russell G , Snively BM , O'Shea TM . Adiposity in adolescent offspring born prematurely to mothers with preeclampsia. J Pediatr 162: 912‐917, 2013. doi: 10.1016/j.jpeds.2012.10.044.
 229. Weinberg J , Sliwowska JH , Lan N , Hellemans KG . Prenatal alcohol exposure: Foetal programming, the hypothalamic‐pituitary‐adrenal axis and sex differences in outcome. J Neuroendocrinol 20: 470‐488, 2008. doi: 10.1111/j.1365‐2826.2008.01669.x.
 230. Weitz G , Wellhoener P , Heindl S , Fehm HL , Dodt C . Relationship between metabolic parameters, blood pressure, and sympathoendocrine function in healthy young adults with low birth weight. Exp Clin Endocrinol Diabetes 113: 444‐450, 2005.
 231. West NA , Crume TL , Maligie MA , Dabelea D . Cardiovascular risk factors in children exposed to maternal diabetes in utero. Diabetologia 54: 504‐507, 2011. doi: 10.1007/s00125‐010‐2008‐1.
 232. White SL , Perkovic V , Cass A , Chang CL , Poulter NR , Spector T , Haysom L , Craig JC , Salmi IA , Chadban SJ , Huxley RR . Is low birth weight an antecedent of CKD in later life? A systematic review of observational studies. Am J Kidney Dis 54: 248‐261, 2009. doi: 10.1053/j.ajkd.2008.12.042.
 233. White CL , Pistell PJ , Purpera MN , Gupta S , Fernandez‐Kim SO , Hise TL , Keller JN , Ingram DK , Morrison CD , Bruce‐Keller AJ . Effects of high fat diet on Morris maze performance, oxidative stress, and inflammation in rats: Contributions of maternal diet. Neurobiol Dis 35: 3‐13, 2009. doi: 10.1016/j.nbd.2009.04.002.
 234. Widdowson EM , McCance RA . Physiological undernutrition in the newborn guinea‐pig. Br J Nutr 9: 316‐321, 1955.
 235. Wilcox CS , Gutterman D . Focus on oxidative stress in the cardiovascular and renal systems. Am J Physiol Heart Circ Physiol 288: H3‐H6, 2005.
 236. Williams SJ , Hemmings DG , Mitchell JM , McMillen IC , Davidge ST . Effects of maternal hypoxia or nutrient restriction during pregnancy on endothelial function in adult male rat offspring. Am J Physiol Heart Circ Physiol 289: H674‐H682, 2005.
 237. Wlodek ME , Mibus A , Tan A , Siebel AL , Owens JA , Moritz KM . Normal lactational environment restores nephron endowment and prevents hypertension after placental restriction in the rat. J Am SocNephrol 18: 1688‐1696, 2007.
 238. Wlodek ME , Westcott K , Siebel AL , Owens JA , Moritz KM . Growth restriction before or after birth reduces nephron number and increases blood pressure in male rats. Kidney Int 74: 187‐195, 2008. doi: 10.1038/ki.2008.153.
 239. Wood CE . Development and programming of the hypothalamus‐pituitary‐adrenal axis. Clin Obstet Gynecol 56: 610‐621, 2013. doi: 10.1097/GRF.0b013e31829e5b15
 240. Woods LL . Maternal glucocorticoids and prenatal programming of hypertension. Am J Physiol Regul Integr Comp Physiol 291: R1069‐R1075, 2006.
 241. Woods LL , Ingelfinger JR , Nyengaard JR , Rasch R . Maternal protein restriction suppresses the newborn renin‐angiotensin system and programs adult hypertension in rats. Pediatr Res 49: 460‐467, 2001.
 242. Woods LL , Ingelfinger JR , Rasch R . Modest maternal protein restriction fails to program adult hypertension in female rats. Am J Physiol Regul Integr Comp Physiol 289: R1131‐R1136, 2005.
 243. Woods LL , Morgan TK , Resko JA . Castration fails to prevent prenatally programmed hypertension in male rats. Am J Physiol Regul Integr Comp Physiol 298: R1111‐R1116, 2010. doi: 10.1152/ajpregu.00803.2009.
 244. Woods LL , Rasch R . Perinatal ANG II programs adult blood pressure, glomerular number and renal function in rats. Am J Physiol Regul Integr Comp Physiol 275: R1593‐R1599, 1998.
 245. Woods LL , Weeks DA . Prenatal programming of adult blood pressure: Role of maternal corticosteroids. Am J Physiol Regul Integr Comp Physiol 289: R955‐R962, 2005.
 246. Woods LL , Weeks DA , Rasch R . Hypertension after neonatal uninephrectomy in rats precedes glomerular damage. Hypertension 38: 337‐342, 2001.
 247. Woods LL , Weeks DA , Rasch R . Programming of adult blood pressure by maternal protein restriction: Role of nephrogenesis. Kidney Int 65: 1339‐1348, 2004.
 248. Wright CS , Rifas‐Shiman SL , Rich‐Edwards JW , Taveras EM , Gillman MW , Oken E . Intrauterine exposure to gestational diabetes, child adiposity, and blood pressure. Am J Hypertens 22: 215‐220, 2009. doi: 10.1038/ajh.2008.326.
 249. Xiao D , Xu Z , Huang X , Longo LD , Yang S , Zhang L . Prenatal gender‐related nicotine exposure increases blood pressure response to angiotensin II in adult offspring. Hypertension 51: 1239‐1247, 2008. doi: 10.1161/HYPERTENSIONAHA.107.106203.
 250. Xiao D , Huang X , Yang S , Zhang L . Antenatal nicotine induces heightened oxidative stress and vascular dysfunction in rat offspring. Br J Pharmacol 164: 1400‐1409, 2011. doi: 10.1111/j.1476‐5381.2011.01437.x.
 251. Xiao D , Huang X , Yang S , Zhang L . Estrogen normalizes perinatal nicotine‐induced hypertensive responses in adult female rat offspring. Hypertension 61: 1246‐1254, 2013. doi: 10.1161/HYPERTENSIONAHA.113.01152.
 252. Xu Y , Williams SJ , O'Brien D , Davidge ST . Hypoxia or nutrient restriction during pregnancy in rats leads to progressive cardiac remodeling and impairs post‐ischemic recovery in adult male offspring. FASEB J 20: 1251‐1253, 2006.
 253. Yan J , Li X , Su R , Zhang K , Yang H . Long‐term effects of maternal diabetes on blood pressure and renal function in rat male offspring. PLoS One 9: e88269, 2014. doi: 10.1371/journal.pone.0088269.
 254. Young JB . Programming of sympathoadrenal function. Trends Endocrinol Metab 13: 381‐385, 2002.
 255. Yvan‐Charvet L , Even P , Bloch‐Faure M , Guerre‐Millo M , Moustaid‐Moussa N , Ferre P , Quignard‐Boulange A . Deletion of the angiotensin type 2 receptor (AT2R) reduces adipose cell size and protects from diet‐induced obesity and insulin resistance. Diabetes. 54: 991‐999, 2005.
 256. Zheng S , Rollet M , Pan YX . Protein restriction during gestation alters histone modifications at the glucose transporter 4 (GLUT4) promoter region and induces GLUT4 expression in skeletal muscle of female rat offspring. J Nutr Biochem 23: 1064‐1071, 2012. doi: 10.1016/j.jnutbio.2011.05.013.

FURTHER READING

Boubred F, Saint-Faust M, Buffat C, Ligi I, Grandvuillemin I, Simeoni U. Developmental origins of chronic renal disease: an integrative hypothesis. Int J Nephrol 2013: 346067, 2013.

Gatford KL, Simmons RA. Prenatal programming of insulin secretion in intrauterine growth restriction. Clin Obstet Gynecol 56: 520-528, 2013.

Intapad S, Ojeda NB, Dasinger JH, Alexander BT. Sex differences in the developmental origins of cardiovascular disease. Physiology (Bethesda) 29: 122-132, 2014.

Lillycrop KA, Burdge GC. Epigenetic mechanisms linking early nutrition to long term health. Best Pract Res Clin Endocrinol Metab 26: 667-676, 2012.

Luyckx VA, Bertram JF, Brenner BM, Fall C, Hoy WE, Ozanne SE, Vikse BE. Effect of fetal and child health on kidney development and long-term risk of hypertension and kidney disease. Lancet 382: 273-283, 2013.

Moritz KM, Cuffe JS, Wilson LB, Dickinson H, Wlodek ME, Simmons DG, Denton KM. Review: Sex specific programming: a critical role for the renal renin-angiotensin system. Placenta 31: S40-S46, 2010.

Nijland MJ, Ford SP, Nathanielsz PW. Prenatal origins of adult disease. Curr Opin Obstet Gynecol 20:132-138, 2008.

Segovia SA, Vickers MH, Gray C Reynolds CM. Maternal obesity, inflammation, and developmental programming. Biomed Res Int 2014:418975, 2014.


Related Articles:

Hypertension: Physiology and Pathophysiology
Interaction of Stress and Dietary NaCl Intake in Hypertension: Renal Neural Mechanisms
Renin–Angiotensin–Aldosterone System and the Renal Regulation of Sodium, Potassium, and Blood Pressure Homeostasis
Diabetes and Obesity
Pulmonary Vascular Disease
Systemic Hypertension

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Fetal Programming and Cardiovascular Pathology
 

How to Cite

Barbara T. Alexander, John Henry Dasinger, Suttira Intapad. Fetal Programming and Cardiovascular Pathology. Compr Physiol 2015, 5: 997-1025. doi: 10.1002/cphy.c140036