Endocrine Abstracts

Polycystic ovary syndrome (PCOS) is the most common cause of infertility in reproductive aged women affecting ~5–10% of women of reproductive age worldwide. PCOS patients are characterized by infertility disorders, obesity, insulin resistance and hyperandrogenemia that persists during pregnancy. This finding allowed to suggest the hypothesis that this intrauterine environment could affect the fetus, reprogramming the insulin sensitivity of the offspring. We have developed an ovine model to study the reprogramming effect of testosterone (T) during pregnancy in order to emulate the hyperandrogenemia observed in PCO pregnant mothers. The objective of this work was to assess the morphometry of fetal tissues and the mRNA expression of key molecules in the insulin pathway of insulin sensitivity tissues in ovine female fetal tissues exposed to T in utero. Pregnant Suffolk-down sheep were treated with 30 mg T propionate twice weekly from day 30–90 of pregnancy and 40 mg from day 90 to 120 of pregnancy. Pregnant control sheep received the vehicle of T. At 120 days of pregnancy and under bioethical procedures, female fetuses were obtained by cesarean surgery. Fetal skeletal muscle, visceral adipose tissue and pancreas were collected for morphological (HE and NADH-Tr stain) and RNA expression of insulin receptor (IR), insulin receptor substrate 1 and 2 (IRS-1, 2), AKT, PKC and glucose transporters (GLUT2 and GLUT4). Control and T- fetuses showed similar pattern in the development of skeletal muscle (number of fibers, CSA and proportional phenotype of fibers), adipose tissue (area and perimeter of adipocyte) and pancreas (islet area and number of islets). On the other hand, there was higher expression of IR signaling factors and GLUT2 and GLUT4 in pancreas. These results provide evidence that T induces transcriptional activation of insulin signaling in our animal model of PCOS without effect on morphological organogenesis.