# Effects of Androgen and Diet on Uterine-Placental Function

> **NIH NIH P50** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $232,722

## Abstract

SUMMARY/ABSTRACT
Hyperandrogenism combined with obesity are clinical hallmarks of polycystic ovary syndrome (PCOS), a
complex disorder affecting ~10% of reproductive-aged women. Many women with androgen excess (AE) also
display “metabolic syndrome” with insulin resistance, hyperinsulinemia, and impaired glucose tolerance. These
women often have subfertility associated with menstrual cycle irregularities. Even in women with normal
cycles, AE and metabolic syndrome correlate with impaired endometrial and placental function leading to poor
reproductive outcome. In this NCTRI center, we will interrogate the actions and interactions of AE and diet on
reproductive health with the goal of improving fertility in women with AE and metabolic syndrome. Our premise
is that AE and/or exposure to an obesogenic diet, disrupts endometrial and placental physiology. To discern
the actions and interactions of AE and diet on reproductive function, we are chronically treating young female
macaques with mildly elevated testosterone (T), in the presence or absence of an obesogenic western-style
diet (WSD). Our intent is to mimic the conditions in adolescent girls at risk for developing PCOS. We report that
after 3-4 years of treatment, the T and T + WSD groups exhibit impaired ovarian and endometrial function,
attenuated placental vascular perfusion, and reduced pregnancy rate. These animals are now being treated for
5 years. Our hypothesis is that continued exposure to T and/or WSD will further deteriorate uterine and
placental function and exacerbate the effect on reproductive success. To test this hypothesis, we will continue
treatment for an additional year and conduct longitudinal studies on endometrial/placental function and fertility.
The treatments will then be stopped, and we will test the hypothesis that treatment removal restores
uterine/placental phenotype and fertility. Our specific aims are: 1) To characterize the long-term effect of T
and/or WSD on endometrial morphology, markers of endometrial receptivity, placental function, and
metabolism; 2) To utilize contrast-enhanced ultrasound imaging (CEUS) to identify vascular compromise in the
endometrium and placenta associated with T and/or WSD; 3) To determine whether T and/or WSD
exacerbates inflammation in the endometrium and placenta using in vivo molecular detection of inflammation
by CEUS, and correlating it to immunohistological markers; and, 4) To determine if withdrawal of T and WSD
treatments returns the endometrium to a normal pre-implantation phenotype, and restores placental physiology
leading to normal reproductive outcome. Results of this research will be correlated with metabolic and ovarian
effects identified in NCTRI projects I and II.

## Key facts

- **NIH application ID:** 10136653
- **Project number:** 5P50HD071836-09
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** OV D SLAYDEN
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $232,722
- **Award type:** 5
- **Project period:** 2013-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136653

## Citation

> US National Institutes of Health, RePORTER application 10136653, Effects of Androgen and Diet on Uterine-Placental Function (5P50HD071836-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10136653. Licensed CC0.

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