Developmental programming: Preconceptional and gestational exposure of sheep to biosolids on offspring ovarian dynamics.

Developmental exposure to environmental chemicals (ECs) perturbs establishment and maintenance of the ovarian reserve across the reproductive lifetime, leading to premature follicle depletion and ovarian aging. Considering humans are exposed to a complex mixture of ECs, real-life models assessing their cumulative impact on the ovarian reserve are needed. Biosolids is a source of real-life mixture of ECs. While earlier studies demonstrated that grazing pregnant sheep on biosolids-treated pastures (BTP) did not influence establishment of the ovarian reserve in fetal life, its impact on subsequent depletion of ovarian reserve during reproductive life of offspring is unknown. We hypothesized that developmental exposure to biosolids accelerates depletion of ovarian reserve. Ovaries were collected from F1 juveniles (9.5 weeks) and adults (2.5 years) born to F0 ewes grazed on control inorganic fertilizer pastures or BTP from before conception and throughout gestation. The impact on follicular density, activation rate, and Anti-Müllerian hormone (AMH; mediator of activation) expression by immunohistochemistry was determined. Activation rate was increased in F1 BTP juveniles with a corresponding reduction in primordial follicle density. In contrast, activation rate and ovarian reserve were similar between control and F1 BTP adults. The density of AMH-positive antral follicles was lower in BTP juveniles, whereas AMH expression tended to be higher in antral follicles of BTP adults, consistent with the changes in the ovarian reserve. These findings of detrimental effects of developmental exposure to biosolids during juvenile life that normalizes in adults is supportive of a shift in activation rate likely related to peripubertal hormonal changes.