Preventing and correcting polycystic ovary syndrome by targeting anti-Müllerian hormone signaling in minipuberty and adulthood in mice

Abstract

Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women, causes significant reproductive and metabolic comorbidities, with no current cure. Gestational androgen and anti-Müllerian hormone (AMH) excess are linked to PCOS, and prenatal aberrant exposure to these hormones induces PCOS-like traits in animal models. However, whether the AMH effects on PCOS programming could extend to early postnatal life remains unknown. Clinical observations showed higher AMH levels during minipuberty in infants of mothers with PCOS, but whether this contributes to PCOS development is uncertain. Here, we show that exposure to high AMH levels during minipuberty in mice causes PCOS-like reproductive and metabolic defects in both sexes. A neutralizing antibody targeting AMH receptor 2 (AMHR2) prevented these defects when administered during minipuberty and alleviated symptoms when given in adulthood. These findings highlight the causal role of elevated AMH in PCOS and suggest AMHR2-targeting therapy as a potential preventive or curative approach.