The present study demonstrates a significant increase in androgen concentrations during pregnancy in PCOS women. We propose that these androgen concentrations could provide a potential source of androgen excess for the fetus, without leading to fetal virilization.

PCOS mothers showed a significantly higher prevalence of SGA newborns which cannot be completely attributed to pregnancy complications, and seems to be more related to the PCOS condition of the mother.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of reproductive-aged women and is exacerbated by obesity. Exposure of ewes to excess testosterone (T) from d 30-90 of gestation culminates in anovulation, functional hyperandrogenism, LH excess, and polyfollicular ovaries, features similar to those of women with PCOS, with some reproductive defects programmed by androgenic actions of T and others not. Excess weight gain during postnatal life increases the severity of these reproductive defects. Prenatal T-treated ewes also manifest reduced insulin sensitivity, a feature found in more than 70% of PCOS women. We tested the hypotheses that reduced insulin sensitivity of prenatal T-treated ewes is programmed by androgenic actions of T, and excess postnatal weight gain exaggerates this defect. In addition, we tested whether disruptive effects of excess weight gain on insulin sensitivity index are transferred to female offspring. Insulin sensitivity was assessed using iv glucose tolerance tests. Results revealed that disruptive effects of prenatal T excess on insulin sensitivity were programmed by androgenic action of T and postnatal overfeeding-impaired insulin sensitivity in both T-treated and controls and that prenatal T-treated sheep tend to manifest such overfeeding impairments earlier than controls. Importantly, offspring of overweight controls also manifest defects in insulin dynamics supportive of intergenerational transfer of obesity-related traits. The findings are of relevance in the context of developmental programming of insulin resistance by prenatal steroids and excess weight gain.

Prenatally testosterone (T)-treated female sheep exhibit ovarian and endocrinological features that resemble those of women with polycystic ovarian syndrome (PCOS), which include luteinizing hormone excess, polyfollicular ovaries, functional hyperandrogenism, and anovulation. In this study, we determined the developmental impact of prenatal T treatment on insulin sensitivity indexes (ISI), a variable that is affected in a majority of PCOS women. Pregnant ewes were treated with 60 mg testosterone propionate intramuscularly in cottonseed oil two times a week or vehicle [control (C)] from days 30 to 90 of gestation. T-females weighed less than C-females or males (P < 0.05) at birth and at 5 wk of age. T-females had an increased anogenital ratio. An intravenous glucose tolerance test followed by an insulin tolerance test conducted after an overnight fast at 5, 20, and 30 wk of age (n = 7-8/group) revealed that ISI were higher at 5 than 30 wk of age in C-females, reflective of a developing insulin resistance associated with puberty. T-females had higher basal insulin levels, higher fasting insulin-to-glucose ratio, and higher incremental area under the insulin curve to the glucose challenge. The ISI of T-females was similar to that of males. No differences in ISI were evident between groups at 20 and 30 wk of age. Mean basal plasma glucose concentrations and glucose disappearance and uptake did not differ between groups at any age. Our findings suggest that prenatal T treatment leads to offspring with reduced birth weight and impaired insulin sensitivity in early postnatal life.

The reproductive system is extremely susceptible to insults from exposure to exogenous steroids during development. Excess prenatal testosterone exposure programs neuroendocrine, ovarian, and metabolic deficits in the female, features seen in women with polycystic ovary disease. The objective of this study was to determine whether prenatal testosterone excess also disrupts the male reproductive system, using sheep as a model system. The extent of reproductive disruption was tested by assessing sperm quantity and quality as well as Leydig cell responsiveness to human chorionic gonadotropin. Males born to mothers treated with 30 mg testosterone propionate twice weekly from d 30 to 90 and with 40 mg testosterone propionate from d 90 to 120 of pregnancy (T-males) showed a significant reduction (P < 0.05) in body weight, scrotal circumference, and sperm count compared with control males. Mean straight line velocity of sperms was also lower in T-males (P < 0.05). Circulating testosterone levels in response to the human chorionic gonadotropin did not differ between groups. These findings demonstrate that exposure to excess testosterone during fetal development has a negative impact on reproductive health of the male offspring, raising concerns relative to unintended human exposure to steroidal mimics in the environment.