# Gestational Hyperandrogenism in Cardiovascular Programming

> **NIH NIH R01** · CALIFORNIA NORTHSTATE UNIVERSITY · 2020 · $743,522

## Abstract

Cardiovascular disease (CVD) is one of the leading causes of death worldwide accounting for 32.2% of all
deaths in the United States. Compelling epidemiological data in human has shown that adverse in utero
environment leads to intrauterine growth restriction that has been associated with increased risk of CVD and
left ventricular hypertrophy. Prenatal exposure to excess testosterone (T) has been found to adversely
program multiple organ systems in the well-validated sheep model of developmental programming. Prenatal T
excess induces IUGR in both sexes in this model and culminates in insulin resistance, increased left ventricular
mass and hypertension in the female offspring in adulthood (the impact of prenatal T on cardiometabolic
outcomes in the male offspring has not been studied). Considering the sexual dimorphism that exists in CVD
mortality and morbidity it is critically important to gain an insight into the role sexual dimorphism plays in left
ventricular hypertrophy to enable development of sex-specific prevention strategies. In this regard, the prenatal
T model provides a valuable resource to determine to what extent excess sex steroid exposure via disease
states (Polycystic ovary syndrome, Congenital adrenal hyperplasia, or environmental chemicals with
steroidogenic potential during fetal development programs adverse cardiac tissue remodeling resulting in
increased mortality from CVD in adulthood. Our preliminary data provide evidence that prenatal T excess leads
to pathological left ventricular remodeling in adult female offspring thus allowing us to probe underlying
mechanisms and sex-specific functional outcomes. The objective of this application is to identify the
mechanism(s) by which in utero exposure to excess T programs adverse cardiac remodeling and susceptibility
to cardiac disease during adult life and to discern sex differences that might exist in this programming. We
hypothesize that prenatal T excess will lead to adverse left ventricular structural and functional changes over
the lifespan and these changes will be driven by epigenetic modifications of pathways involved in maintaining
left ventricular morphology and function leading to increased susceptibility to insult later in life. The proposed
studies will provide insight into the 1) mechanisms by which excess T in-utero leads to adverse left ventricular
remodeling, 2) long term cardiac functional and structural consequences of prenatal T excess and 3) sex
differences in prenatal cardiac programming. Knowledge gained through these studies will help identify
strategies targeted toward treatment for LVH and heart failure and of translational relevance.

## Key facts

- **NIH application ID:** 9971301
- **Project number:** 1R01HL139639-01A1
- **Recipient organization:** CALIFORNIA NORTHSTATE UNIVERSITY
- **Principal Investigator:** VASANTHA PADMANABHAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $743,522
- **Award type:** 1
- **Project period:** 2020-09-04 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971301

## Citation

> US National Institutes of Health, RePORTER application 9971301, Gestational Hyperandrogenism in Cardiovascular Programming (1R01HL139639-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9971301. Licensed CC0.

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