Prenatal perfluorooctanoic sulfonate exposure is associated with polycystic ovary syndrome-like and related traits in female offspring mice.

Abstract

Polycystic Ovary Syndrome (PCOS), is the most common female endocrine disorder affecting women of reproductive age. Its prevalence is estimated to be up to 13 % worldwide. This heterogeneous clinical condition is characterized by marked clinical and/or biochemical hyperandrogenism, ovulatory dysfunction, and frequent development of polycystic ovaries. Several studies have focused on the relationship between endocrine-disrupting pollutants and PCOS development. Perfluorooctanesulfonate (PFOS) is ubiquitously detected in the environment. Exposure to endocrine-disrupting chemicals, including PFOS, during early fetal development may lead to alterations similar to the PCOS phenotype. Using mice as a model, we compared the effects of prenatal exposure to PFOS or dihydrotestosterone (a model of PCOS induction). After analyzing steroid status, we detected delayed pubertal onset accompanied by increased testosterone concentrations in adulthood, as well as altered estrous cycles with a longer metestrus phase. At this point, two of three Rotterdam criteria have been confirmed as PCOS features. Finally, we identified endocrine disruption in the ovaries from adult females prenatally exposed to PFOS, as evidenced by altered expression of genes involved in steroidogenesis pathways, as well as altered expression of gonadotropin hormone receptors, and Amh signaling. These data support a role of PFOS in endocrine disruption and in promoting development of PCOS symptom development.