Discrete fetal
androgen excess during early gestation in rhesus monkeys (Macaca mulatta) promotes endocrine antecedents of adult
polycystic ovary syndrome (PCOS)-like traits in female offspring. Because developmental changes promoting such PCOS-like metabolic dysfunction remain unclear, the present study examined time-mated, gravid rhesus monkeys with female fetuses, of which nine gravid females received 15 mg of
testosterone propionate (TP) subcutaneously daily from 40 to 80 days (first to second trimesters) of gestation [term, mean (range): 165 (155-175) days], whereas an additional six such females received oil vehicle
injections over the same time interval. During gestation, ultrasonography quantified fetal growth measures and was used as an adjunct for fetal blood collections. At term, all fetuses were delivered by
cesarean section for postnatal studies. Blood samples were collected from dams and infants for
glucose,
insulin, and total
free fatty acid (FFA) determinations. TP
injections transiently accelerated
maternal weight gain in dams, very modestly increased head diameter of prenatally androgenized (PA) fetuses, and modestly increased
weight gain in infancy compared with concurrent controls. Mild to moderate
glucose intolerance, with increased area-under-the-curve circulating
insulin values, occurred in TP-injected dams during an intravenous
glucose tolerance test in the early second trimester. Moreover, reduced circulating FFA levels occurred in PA fetuses during a third trimester intravenous
glucagon-
tolbutamide challenge (140 days gestation), whereas excessive
insulin sensitivity and increased insulin secretion relative to
insulin sensitivity occurred in PA infants during an intravenous
glucose-
tolbutamide test at ∼1.5 mo postnatal age. Data from these studies suggest that experimentally induced fetal
androgen excess may result in transient hyperglycemic episodes in the intrauterine environment that are sufficient to induce relative increases in pancreatic function in PA infants, suggesting in this nonhuman primate model that differential programming of
insulin action and secretion may precede adult metabolic dysfunction.