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

Hyperandrogenic disorders, such as polycystic ovary syndrome, are often associated with metabolic disruptions such as insulin resistance and hyperinsulinemia. Studies in sheep, a precocial model of translational relevance, provide evidence that in utero exposure to excess testosterone during days 30–90 of gestation (the sexually dimorphic window where males naturally experience elevated androgens) programs insulin resistance and hyperinsulinemia in female offspring. Extending earlier findings that adverse effects of testosterone excess are evident in fetal day 90 pancreas, the end of testosterone treatment, the present study provides evidence that transcriptomic and phenotypic effects of in utero testosterone excess on female pancreas persist after cessation of treatment, suggesting lasting organizational changes, and induce a male-like phenotype in female pancreas. These findings demonstrate that the female pancreas is susceptible to programmed masculinization during the sexually dimorphic window of fetal development and shed light on underlying connections between hyperandrogenism and metabolic homeostasis. • Exposure to excess testosterone programs masculinization of female sheep pancreas. • Programming of beta-cell phenotype parallels transcriptomic masculinization. • Pancreatic alpha-cell phenotype is inconsistent with masculinization. • Fetal beta- and alpha-cell changes may underlie adverse adult pancreatic phenotype. [ABSTRACT FROM AUTHOR]