# Ovarian Structure-Function: Influence of Androgen and Diet

> **NIH NIH P50** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $176,864

## Abstract

SUMMARY
Elevated circulating androgen (testosterone; T) and a typical high-fat western-style diet (WSD) are associated
with the development of female reproductive disorders, such as polycystic ovary syndrome (PCOS) and
reduced fertility. Although the underlying etiology of reproductive dysfunction in PCOS likely includes altered in
utero programming and genetic contributions, the pathophysiology of exposure to elevated T at PCOS levels of
hyperandrogenemia, WSD, or their combined effects on female fertility is poorly understood, particularly in
primates. The current NCTRI established that chronic T and/or WSD treatment beginning just prior to puberty
in a nonhuman primate model negatively affects reproductive processes critical for fertility. Through 4 years of
treatment, significant effects of T and/or WSD were noted relative to untreated controls in terms of ovarian
function, including: the appearance and persistence of numerous small antral follicles typical of a “polycystic”
ovarian morphology, reduced ovarian vascular function and luteal progesterone synthesis, altered
perivoulatory follicle gene expression, and the presence of degenerated oocytes within the naturally-selected,
single ovulatory follicle. Even if the oocyte from T and/or WSD-treated animals appeared healthy and
meiotically mature, it often showed abnormal cell division kinetics after fertilization. These ovarian defects
correlated with fertility outcomes since exposure to T delayed the time to pregnancy, whereas WSD,
particularly in combination with T, reduced overall fertility and led to abnormal, nonviable pregnancies. WSD-
treated animals that failed to become pregnant exhibited the greatest level of pre-pregnancy and pregnancy
associated metabolic abnormalities, including increased insulin resistance. Although prepubertal exposure to T
and/or WSD significantly affected ovarian processes and fertility relative to controls, treatment did not impact
all animals equally and many continued menstrual cyclicity. Thus, studies are proposed in this NCTRI renewal
(Project II) to determine whether continued T and/or WSD treatment worsens ovarian dysfunction and if
treatment removal restores ovarian physiology, oocyte/embryo quality and fertility. Experiments will continue
during 7 years of T and/or WSD treatment to assess their effects on ovarian follicle growth and development,
intrafollicular events necessary for ovulation, luteal progesterone synthesis, and ovarian vascular function,
relative to controls (Aim 1). The impact of continued T and/or WSD treatment on oocyte health, fertilization,
expression of certain epigenetic factors important for the oocyte-to-embryo transition, as well as embryonic
development and chromosomal integrity will also be assessed (Aim 2). After 7 years, T and WSD treatments
will cease to determine if ovarian function and oocyte/embryo health is restored (Aim 3) similar to what is
observed in age-matched controls. Continued treatment and cessation on ov...

## Key facts

- **NIH application ID:** 10136650
- **Project number:** 5P50HD071836-09
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Jon D Hennebold
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $176,864
- **Award type:** 5
- **Project period:** 2013-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136650

## Citation

> US National Institutes of Health, RePORTER application 10136650, Ovarian Structure-Function: Influence of Androgen and Diet (5P50HD071836-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10136650. Licensed CC0.

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