# Multigenerational Effects of Gestational Testosterone Excess

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $150,840

## Abstract

ABSTRACT
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age,
affecting ~5 million women in the U.S. and over 100 million globally. Clinical and animal studies provide strong
evidence indicating that elevated androgen levels in utero increase the offspring’s susceptibility to develop the
PCOS phenotype. The metabolic system is particularly susceptible to the deleterious effects of prenatal
androgen excess. Studies in sheep demonstrate that prenatal exposure to testosterone excess results in
postnatal development of numerous cardiometabolic perturbations, including insulin resistance, increased
adiposity, altered adipocyte size and distribution, and hypertension. Therefore, prenatal androgen excess
impacts both the reproductive and metabolic systems, and reproductive perturbations (e.g., functional
hyperandrogenism) impair metabolic function, whereas metabolic imbalances (e.g., insulin resistance and
hyperinsulinemia) can impact reproductive function, thus forming a vicious cycle. Postnatal adiposity enhances
the severity of the impact of prenatal testosterone excess. Consequently, interventions targeting multiple organ
systems may be needed to prevent the manifestation of adverse outcomes programmed prenatally. Recent
research provides strong evidence for the involvement of epigenetic processes, such as DNA
methylation, in the etiology of PCOS. Because studies involving human tissues are less feasible,
particularly those involving neuroendocrine and metabolic tissues, animal models of PCOS phenotype
provide valuable tissue resources to answer mechanistic questions. We propose to study the impact of
prenatal T excess and postnatal adiposity on transcriptome and epigenome of the arcuate nucleus,
liver and adipocyte tissue, Our studies will help advance our fundamental understanding of the
organizational role that androgens play in organ development and elucidate the epigenetic and
transcriptional mechanisms mediating the effects of prenatal T excess on metabolic and reproductive
health in this sheep model. A better understanding of the epigenetic and transcriptional mediators of
metabolic dysfunction in this sheep model of PCOS can aid in the future development of targeted
interventions.

## Key facts

- **NIH application ID:** 10472234
- **Project number:** 3R01HD099096-02S1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Rodolfo C. Cardoso
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $150,840
- **Award type:** 3
- **Project period:** 2020-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10472234

## Citation

> US National Institutes of Health, RePORTER application 10472234, Multigenerational Effects of Gestational Testosterone Excess (3R01HD099096-02S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10472234. Licensed CC0.

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