Sex Differences in the Fetal Programming of Hypertension

Overview

Journal Gend Med

Specialty General Medicine

Date 2008 May 28

PMID 18395678

Citations 93

Authors

Daniela Grigore

Norma B Ojeda

Barbara T Alexander

Affiliations

Soon will be listed here.

Abstract

Background: Numerous clinical and experimental studies support the hypothesis that the intrauterine environment is an important determinant of cardiovascular disease and hypertension.

Objective: This review examined the mechanisms linking an adverse fetal environment and increased risk for chronic disease in adulthood with an emphasis on gender differences and the role of sex hormones in mediating sexual dimorphism in response to a suboptimal fetal environment.

Methods: This review focuses on current findings from the PubMed database regarding animal models of fetal programming of hypertension, sex differences in phenotypic outcomes, and potential mechanisms in offspring of mothers exposed to an adverse insult during gestation. For the years 1988 to 2007, the database was searched using the following terms: fetal programming, intrauterine growth restriction, low birth weight, sex differences, estradiol, testosterone, high blood pressure, and hypertension.

Results: The mechanisms involved in the fetal programming of adult disease are multifactorial and include alterations in the regulatory systems affecting the long-tterm control of arterial pressure. Sex differences have been observed in animal models of fetal programming, and recent studies suggest that sex hormones may modulate activity of regulatory systems, leading to a lower incidence of hypertension and vascular dysfunction in females compared with males.

Conclusions: Animal models of fetal programming provide critical support for the inverse relationship between birth weight and blood pressure. Experimental models demonstrate that sex differences are observed in the pathophysiologic response to an adverse fetal environment. A role for sex hormone involvement is strongly suggested,with modulation of the renin-angiotensin system as a possible mechanism.

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References

Vehaskari V, Woods L . Prenatal programming of hypertension: lessons from experimental models. J Am Soc Nephrol. 2005; 16(9):2545-56. DOI: 10.1681/ASN.2005030300. View

Sokol R, Okuda H, Stanczyk F, Wolfe G, Delaney J, Chapin R . Normative reproductive indices for male and female adult Sprague-Dawley rats. Contraception. 1999; 59(3):203-7. DOI: 10.1016/s0010-7824(99)00017-7. View

Haycock G . Relationship between birth weight, glomerular number, and glomerular size. Kidney Int. 2001; 59(1):387. DOI: 10.1046/j.1523-1755.2001.00509.x. View

Hinchliffe S, LYNCH M, Sargent P, Howard C, van Velzen D . The effect of intrauterine growth retardation on the development of renal nephrons. Br J Obstet Gynaecol. 1992; 99(4):296-301. DOI: 10.1111/j.1471-0528.1992.tb13726.x. View

Ozaki T, Nishina H, Hanson M, Poston L . Dietary restriction in pregnant rats causes gender-related hypertension and vascular dysfunction in offspring. J Physiol. 2001; 530(Pt 1):141-52. PMC: 2278385. DOI: 10.1111/j.1469-7793.2001.0141m.x. View

Staessen J, Wang J, Bianchi G, Birkenhager W . Essential hypertension. Lancet. 2003; 361(9369):1629-41. DOI: 10.1016/S0140-6736(03)13302-8. View

Dodic M, Abouantoun T, OConnor A, Wintour E, Moritz K . Programming effects of short prenatal exposure to dexamethasone in sheep. Hypertension. 2002; 40(5):729-34. DOI: 10.1161/01.hyp.0000036455.62159.7e. View

Forsen T, Osmond C, Eriksson J, Barker D . Growth of girls who later develop coronary heart disease. Heart. 2003; 90(1):20-4. PMC: 1768015. DOI: 10.1136/heart.90.1.20. View

Roberts C, Vaziri N, Barnard R . Protective effects of estrogen on gender-specific development of diet-induced hypertension. J Appl Physiol (1985). 2001; 91(5):2005-9. DOI: 10.1152/jappl.2001.91.5.2005. View

10.

Kett M, Bertram J . Nephron endowment and blood pressure: what do we really know?. Curr Hypertens Rep. 2004; 6(2):133-9. DOI: 10.1007/s11906-004-0089-2. View

11.

Guron G, Friberg P . An intact renin-angiotensin system is a prerequisite for normal renal development. J Hypertens. 2000; 18(2):123-37. DOI: 10.1097/00004872-200018020-00001. View

12.

Bertram C, Trowern A, Copin N, Jackson A, Whorwood C . The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11beta-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero. Endocrinology. 2001; 142(7):2841-53. DOI: 10.1210/endo.142.7.8238. View

13.

Cetin I, Foidart J, Miozzo M, Raun T, Jansson T, Tsatsaris V . Fetal growth restriction: a workshop report. Placenta. 2004; 25(8-9):753-7. DOI: 10.1016/j.placenta.2004.02.004. View

14.

McMillen I, Robinson J . Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev. 2005; 85(2):571-633. DOI: 10.1152/physrev.00053.2003. View

15.

Manalich R, Reyes L, Herrera M, Melendi C, Fundora I . Relationship between weight at birth and the number and size of renal glomeruli in humans: a histomorphometric study. Kidney Int. 2000; 58(2):770-3. DOI: 10.1046/j.1523-1755.2000.00225.x. View

16.

Vehaskari V, Aviles D, Manning J . Prenatal programming of adult hypertension in the rat. Kidney Int. 2001; 59(1):238-45. DOI: 10.1046/j.1523-1755.2001.00484.x. View

17.

Hinchliffe S, Sargent P, Howard C, Chan Y, van Velzen D . Human intrauterine renal growth expressed in absolute number of glomeruli assessed by the disector method and Cavalieri principle. Lab Invest. 1991; 64(6):777-84. View

18.

Ortiz L, Quan A, Zarzar F, Weinberg A, Baum M . Prenatal dexamethasone programs hypertension and renal injury in the rat. Hypertension. 2003; 41(2):328-34. PMC: 4127977. DOI: 10.1161/01.hyp.0000049763.51269.51. View

19.

Panza J, Quyyumi A, Brush Jr J, Epstein S . Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med. 1990; 323(1):22-7. DOI: 10.1056/NEJM199007053230105. View

20.

Drake A, Walker B . The intergenerational effects of fetal programming: non-genomic mechanisms for the inheritance of low birth weight and cardiovascular risk. J Endocrinol. 2004; 180(1):1-16. DOI: 10.1677/joe.0.1800001. View