Developmental programming: Impact of prenatal testosterone treatment and postnatal obesity on ovarian follicular...

Prenatal testosterone (T) excess leads to reproductive dysfunctions in sheep with obesity exaggerating such defects. Developmental studies found ovarian reserve is similar in control and prenatal T sheep at fetal day 140, with prenatal T females showing increased follicular recruitment and persistence at 10 months of age (postpubertal). This study tested if prenatal T sheep show accelerated depletion prepubertally and if depletion of ovarian reserve would explain loss of cyclicity in prenatal T females and its amplification by postnatal obesity. Stereological examinations were performed at 5 (prepubertal, control and prenatal T) and 21 months (control, prenatal T and prenatal T obese, following estrus synchronization) of age. Obesity was induced by overfeeding from weaning. At 5 months, prenatal T females had 46% less primordial follicles than controls (P < 0.01), supportive of increased follicular depletion. Depletion rate was slower and a higher percentage of growing follicles was present in 21 month than 5 month old prenatal T females (P < 0.01). Postnatal obesity did not exaggerate the impact of prenatal T on follicular recruitment indicating that compounding effects of obesity on loss of cyclicity females is not due to depletion of ovarian reserve. Assessment of follicular dynamics across several time points during the reproductive life span (this and earlier study combined) provides evidence supportive of a shift in follicular dynamics in prenatal T females from one of accelerated follicular depletion initiated prior to puberty to stockpiling of growing follicles after puberty, a time point critical in the development of the polycystic ovary syndrome phenotype.