Mechanisms of Sexual Dimorphism in Perinatal Programming

Summary

Principal Investigator: LORI WOODS
Abstract: Numerous human studies have shown that babies born smaller have an increased adult cardiovascular risk compared to larger babies, indicating that factors in the prenatal environment affecting fetal growth can program the individual for increased cardiovascular risk later in life. One of these factors is maternal protein intake. In rats, maternal protein restriction leads to renal dysfunction and hypertension in the adult offspring. Suppression of the intrarenal rennin/angiotensin system during a critical period in development, and a consequent reduction in nephron endowment, appear to play an important role in this programming. Female offspring are relatively protected from the programming effects of several adverse maternal dietary conditions, including protein restriction. In other animal models, the presence of gonadal hormones during development and/or in adulthood contributes to the sexually dimorphic patterns of hypertension, but the mechanisms by which female gender protects against programming for hypertension by maternal diet are not known. The purpose of this project is to determine the mechanisms responsible for the relative protective effect of female Gender on perinatal programming for hypertension. The overarching hypothesis is that the presence or absence of testosterone during development and/or testosterone or estrogen later in life are responsible for the sexual dimorphism of perinatal programming, and specifically, that these gonadal hormones contribute to programming of offspring hypertension at least in part through permitting suppression of the fetal/newborn intrarenal renin angiotensin system and consequent impairment of renal development, resulting in permanent changes in renal structure and function. In these studies, testosterone and estrogen levels in male and female offspring of normal and protein-restricted mothers will be manipulated during the developmental period and/or in adult life by orchiectomy/ovariectomy and administration of exogenous hormone or by administration of pharmacologic inhibitors. Renal renin-angiotensin system components will be measured in the neonatal period, and arterial pressure, renal function, and glomerular number and volume will be measured in juvenile and adult animals.
Funding Period: 2002-04-01 - 2007-03-31
more information: NIH RePORT

Top Publications

  1. pmc Castration fails to prevent prenatally programmed hypertension in male rats
    Lori L Woods
    Department of Pathology, Oregon Health and Science University, Portland, OR 97239 3098, USA
    Am J Physiol Regul Integr Comp Physiol 298:R1111-6. 2010
  2. ncbi Prenatal programming of adult blood pressure: role of maternal corticosteroids
    Lori L Woods
    Division of Nephrology and Hypertension, L463, Oregon Health and Science University, 3181 S W Sam Jackson Park Rd, Portland, OR 97239 3098, USA
    Am J Physiol Regul Integr Comp Physiol 289:R955-62. 2005
  3. ncbi Modest maternal protein restriction fails to program adult hypertension in female rats
    Lori L Woods
    Division of Nephrology and Hypertension, L463, Oregon Health and Science University, 3181 S W Sam Jackson Park Rd, Portland, OR 97239 3098, USA
    Am J Physiol Regul Integr Comp Physiol 289:R1131-6. 2005
  4. ncbi Prenatal programming of hypertension: lessons from experimental models
    V Matti Vehaskari
    Department of Pediatrics, Division of Pediatric Nephrology, Louisiana State University Health Sciences Center, New Orleans, LA 70118, USA
    J Am Soc Nephrol 16:2545-56. 2005
  5. ncbi Maternal glucocorticoids and prenatal programming of hypertension
    Lori L Woods
    Division of Nephrology and Hypertension, L463, Oregon Health and Science Univ, 3181 S W Sam Jackson Park Rd, Portland, OR 97239 3098, USA
    Am J Physiol Regul Integr Comp Physiol 291:R1069-75. 2006
  6. ncbi Maternal nutrition and predisposition to later kidney disease
    Lori L Woods
    Division of Nephrology and Hypertension, Oregon Health and Science University, Portland, OR 97239 3098, USA
    Curr Drug Targets 8:906-13. 2007

Scientific Experts

Detail Information

Publications6

  1. pmc Castration fails to prevent prenatally programmed hypertension in male rats
    Lori L Woods
    Department of Pathology, Oregon Health and Science University, Portland, OR 97239 3098, USA
    Am J Physiol Regul Integr Comp Physiol 298:R1111-6. 2010
    ..However, androgens such as testosterone may promote renal injury in LP males...
  2. ncbi Prenatal programming of adult blood pressure: role of maternal corticosteroids
    Lori L Woods
    Division of Nephrology and Hypertension, L463, Oregon Health and Science University, 3181 S W Sam Jackson Park Rd, Portland, OR 97239 3098, USA
    Am J Physiol Regul Integr Comp Physiol 289:R955-62. 2005
    ..The window of sensitivity of future offspring blood pressure to either maternal insult coincides with nephrogenesis in the rat, suggesting that impaired renal development could play an important role in this programming...
  3. ncbi Modest maternal protein restriction fails to program adult hypertension in female rats
    Lori L Woods
    Division of Nephrology and Hypertension, L463, Oregon Health and Science University, 3181 S W Sam Jackson Park Rd, Portland, OR 97239 3098, USA
    Am J Physiol Regul Integr Comp Physiol 289:R1131-6. 2005
    ..The intrarenal renin-angiotensin system during development may play a key role in this protective effect of female gender...
  4. ncbi Prenatal programming of hypertension: lessons from experimental models
    V Matti Vehaskari
    Department of Pediatrics, Division of Pediatric Nephrology, Louisiana State University Health Sciences Center, New Orleans, LA 70118, USA
    J Am Soc Nephrol 16:2545-56. 2005
  5. ncbi Maternal glucocorticoids and prenatal programming of hypertension
    Lori L Woods
    Division of Nephrology and Hypertension, L463, Oregon Health and Science Univ, 3181 S W Sam Jackson Park Rd, Portland, OR 97239 3098, USA
    Am J Physiol Regul Integr Comp Physiol 291:R1069-75. 2006
    ..These data do not support the hypothesis that maternal glucocorticoids program offspring hypertension directly...
  6. ncbi Maternal nutrition and predisposition to later kidney disease
    Lori L Woods
    Division of Nephrology and Hypertension, Oregon Health and Science University, Portland, OR 97239 3098, USA
    Curr Drug Targets 8:906-13. 2007
    ....