Fetal programming of adult hypertension in female rat offspring exposed to androgens in utero

K. Sathishkumar, Rebekah Elkins, Uma Yallampalli, Meena Balakrishnan, Chandrasekhar Yallampalli

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Aims: The influence of prenatal factors on the development of arterial hypertension has gained considerable interest in recent years. We examined the effects of prenatal testosterone treatment on blood pressure in adult female rats. Further, to define the mechanisms whereby blood pressure may be raised, we examined vascular endothelial function and nitric oxide synthesis. Methods and Results: Testosterone propionate (0.5. mg/kg/day; SC) or vehicle was administered to pregnant Sprague-Dawley rats from gestational day 15-19. Maternal feed intake and plasma levels of steroid hormones were measured in the dams. In the female offspring, birth weight, growth rate, blood pressure, vascular reactivity, eNOS expression, and nitric oxide production were examined. In the pregnant rats, testosterone-treatment increased plasma testosterone levels by 2-fold without any significant changes in 17β-estradiol, progesterone and corticosterone levels. Testosterone-treatment did not affect maternal feed intake. The pups born to testosterone mothers were smaller in size but exhibited catch-up growth. The blood pressure in the testosterone offspring at 6. months of age was significantly higher compared to controls. Endothelium-intact mesenteric arteries from testosterone group exhibited increased contractile responses to phenylephrine, decreased vasodilation to acetylcholine and unaltered responses to sodium nitroprusside in comparison to control rats. Testosterone rats demonstrated decreased expression for eNOS, and reduced nitric oxide production. Conclusions: Our data show that elevated plasma maternal testosterone levels: (1) causes low birth weight followed by catch-up growth and hypertension in female offspring and (2) alters endothelium-dependent vascular responses. The endothelial dysfunction is associated with decreased activity/expression of eNOS.

Original languageEnglish (US)
Pages (from-to)407-414
Number of pages8
JournalEarly Human Development
Volume87
Issue number6
DOIs
StatePublished - Jun 1 2011

Keywords

  • Blood pressure
  • Endothelium
  • Fetal programming
  • Nitric oxide
  • Pregnancy
  • Testosterone

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology

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    Sathishkumar, K., Elkins, R., Yallampalli, U., Balakrishnan, M., & Yallampalli, C. (2011). Fetal programming of adult hypertension in female rat offspring exposed to androgens in utero. Early Human Development, 87(6), 407-414. https://doi.org/10.1016/j.earlhumdev.2011.03.001