Developmental Programming: Prenatal Testosterone Excess on Ovarian SF1/DAX1/FOXO3

Area of Science:

• Reproductive Endocrinology
• Developmental Biology
• Ovarian Physiology

Background:

• Prenatal androgen excess, a potential factor in polycystic ovarian syndrome (PCOS), influences ovarian development.
• Anti-Mullerian hormone (AMH) levels are altered in PCOS, affecting follicular recruitment and persistence.
• Steroidogenic factor 1 (SF1), DAX1, and FOXO3 are key regulators of ovarian gene expression and follicular dynamics.

Purpose of the Study:

• To investigate the impact of prenatal androgen programming on SF1, DAX1, and FOXO3 protein expression in sheep ovaries.
• To determine if these molecular changes contribute to the follicular phenotypes observed in prenatal androgen-excess models.
• To explore the translational relevance of these findings to human PCOS.

Main Methods:

• Sheep were exposed to prenatal testosterone (T) or dihydrotestosterone (DHT) during gestation.
• Ovarian tissues were collected at fetal day 90, fetal day 140, 1 year, and 2 years of age.
• Immunohistochemistry was used to quantify SF1, DAX1, and FOXO3 protein levels in granulosa and theca cells.

Main Results:

• Prenatal T exposure increased DAX1 and FOXO3 expression at specific developmental stages and SF1 at later stages.
• Prenatal DHT exposure also altered DAX1 and SF1 expression in a time-dependent manner.
• These androgen-induced changes in DAX1/SF1 proteins correlate with altered AMH levels and follicular phenotypes.

Conclusions:

• Androgen programming during prenatal development significantly impacts the expression of SF1, DAX1, and FOXO3 in the sheep ovary.
• These molecular alterations provide a potential mechanism for the enhanced follicular recruitment and persistence observed in prenatal androgen-exposed females.
• The findings offer insights into the developmental origins of PCOS-like ovarian phenotypes and may have translational implications for understanding human reproductive disorders.