Developmental programming: Testosterone excess masculinizes female pancreatic transcriptome and function in sheep.

Area of Science:

• Endocrinology
• Developmental Biology
• Metabolic Syndrome

Background:

• Hyperandrogenic disorders, like polycystic ovary syndrome (PCOS), are linked to metabolic issues including insulin resistance and hyperinsulinemia.
• Sheep are a relevant model for studying fetal development and metabolic programming due to their precocial nature.

Purpose of the Study:

• To investigate the lasting effects of in utero testosterone excess on the female pancreas.
• To determine if fetal exposure to excess androgens induces a male-like phenotype in the female pancreas.

Main Methods:

• Sheep were exposed to excess testosterone during a critical window of gestation (days 30-90).
• Transcriptomic and phenotypic analyses of the pancreas were performed in female offspring after the exposure period.

Main Results:

• In utero testosterone excess caused persistent transcriptomic and phenotypic changes in the female pancreas.
• These changes suggest lasting organizational effects and a programmed masculinization of the female pancreas.
• The study observed a male-like phenotype in the female pancreas following developmental androgen exposure.

Conclusions:

• The female pancreas is vulnerable to masculinization during a specific fetal developmental window.
• Developmental exposure to excess androgens can program long-term metabolic dysfunction and alter pancreatic development.
• These findings link hyperandrogenism to metabolic homeostasis disruptions through developmental programming.