Developmental programming: gestational testosterone treatment alters fetal ovarian gene expression

Area of Science:

• Reproductive Endocrinology
• Developmental Biology
• Genetics

Background:

• Prenatal exposure to excess testosterone (T) is linked to polycystic ovarian morphology and altered follicular dynamics.
• Understanding the molecular mechanisms behind T-induced ovarian changes is crucial for addressing reproductive pathologies.

Purpose of the Study:

• To investigate the effects of prenatal T excess on fetal ovarian gene and microRNA expression.
• To determine whether these alterations are mediated by androgenic or estrogenic actions of T.

Main Methods:

• Pregnant ewes were treated with testosterone (T) or T plus an androgen receptor antagonist (flutamide).
• Fetal ovaries were collected at gestational days 65 and 90.
• Gene expression (RT-PCR) and microRNA expression (microarrays) were analyzed.

Main Results:

• Prenatal T decreased Cyp11a1 expression and increased Cyp19 and 5α-reductase expression in fetal ovaries.
• Flutamide partially blocked T's effects on Cyp11a1 but not on Cyp19 or 5α-reductase.
• Prenatal T altered microRNA expression, including miR-497 and miR-15b.

Conclusions:

• Maternal T treatment reprograms fetal ovarian development through both androgenic and estrogenic pathways.
• These molecular changes contribute to the developmental trajectory leading to adult reproductive issues like PCOS.