Prenatal Androgen Exposure Reduces Ovarian Function

Author

Marlee WeetsFollow

Document Type

Thesis

Date of Degree Completion

Spring 2024

Degree Name

Master of Science (MS)

Department

Biology

Committee Chair

April K. Binder

Second Committee Member

Lucinda Carnell

Third Committee Member

Mary Poulson

Abstract

Polycystic ovary syndrome (PCOS) is the most common reproductive and endocrine disorder, being the leading cause of infertility for females of reproductive age. The etiology of PCOS is not fully known, although it is hypothesized that there is a genetic, epigenetic, and environmental component to the disease. One of the environmental influences that can cause an abnormal reproductive phenotype similar to PCOS is prenatal exposure to excess androgens (male sex hormones). Previous studies have shown that prenatal exposure to androgens in mice can cause a PCOS-like ovarian phenotype similar to people with PCOS. To examine how prenatal androgen exposure causes ovarian dysfunction we used a mouse model of PCOS induced by prenatal exposure of the androgen dihydrotestosterone (DHT). We also used flutamide, an androgen antagonist to examine the mechanism by which androgens may cause reproductive dysfunction. In this study, pregnant dams were treated with either a vehicle control, DHT, flutamide, or DHT + flutamide to expose pups during late gestation. These pups were then observed for the timing of puberty and estrous cycle, measures of the hypothalamic-pituitary-gonadal (HPG) axis. The prenatally exposed mice were also observed for other measures of fertility and reproductive success, such as a continuous breeding study and ovarian response to hormone stimulation. This ovarian response included the number of oocytes ovulated indicating ovulatory capacity, ovarian follicle development, and ovarian gene expression. In the mice prenatally exposed to the androgen DHT, there was a notable absence of puberty and irregular estrous cycling, indicating that prenatal androgen exposure may reprogram the HPG axis to cause dysfunction. The mice prenatally exposed to DHT also had reduced ovulation, differential gene expression, and abnormal ovarian morphology including the formation of cysts. These effects caused by prenatal DHT exposure were recovered in part by treatment with flutamide, suggesting that a PCOS-like ovarian phenotype after prenatal androgen exposure was driven by signaling through the androgen receptor.

Recommended Citation

Weets, Marlee, "Prenatal Androgen Exposure Reduces Ovarian Function" (2024). All Master's Theses. 1949.
https://digitalcommons.cwu.edu/etd/1949