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Prenatal Anti-Müllerian Hormone Treatment in Mice Increases Stress Reactivity Similar to PCOS Phenotype


Polycystic ovary syndrome (PCOS) is a complex infertility disorder affecting up to 10% of women in the U.S. and most commonly presents with anovulation and androgen excess. Previous research has shown that PCOS women have significantly higher levels of anti-Müllerian hormone (AMH) and psychiatric comorbidities. However, the effect of AMH on the neuroendocrine reproductive axis has not been fully characterized. Recently, a novel prenatal AMH (pAMH) mouse model of PCOS was developed to recapitulate reproductive phenotypes of the disorder; but non-reproductive aspects, such as stress and anxiety, have not been explored. This project sought to investigate the effect of pAMH exposure on stress reactivity in two generations of offspring.

We found that pAMH treatment led to increased response to psychosocial stress in both generations of female mice. The pAMH group had significantly increased novelty-induced defecation and urination, and also had an overall significant and prolonged increase in corticosterone (CORT) response to restraint stress. Notably, we also observed pAMH-induced transgenerational effects in male mice.

Our findings suggest that in addition to reproductive phenotypes, pAMH mouse model is also a representative model of PCOS on non-reproductive measures. To our knowledge, this is the first study to address psychiatric domains of PCOS in a mouse model. Our results potentially shed light on a previously unknown action of AMH in the brain and could also have implications for psychiatric disorders within and beyond the context of PCOS. Further investigation is required to identify the neural circuitry involved in pAMH-mediated phenotypes.

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