Anti-Müllerian Hormone Ameliorates Uterine DNA Damage Response and Prevents Pregnancy Complications in Doxorubicin-Treated Mice†.

Abstract

Anti-Müllerian hormone (AMH) is a promising fertoprotective agent, demonstrating a particularly strong efficacy against doxorubicin (DOX)-induced ovarian toxicity. However, the impact of chemotherapy on the uterus, and the potential benefits of AMH in this context, remain poorly understood. In this study, we characterized DOX-induced uterine damage and assessed the fertoprotective effect of AMH co-treatment in mice. Acutely, DOX treatment caused the accumulation of DNA damage in multiple uterine cell types, including the myometrium, as evidenced by both increased γ-H2AX staining and upregulation of Cdkn1a, Trp53 and other downstream Trp53 pathway targets both at mRNA and protein levels. AMH co-treatment counteracted these effects by reducing γ-H2AX-positive DNA damage accumulation as well as suppressing Trp53 and Trp53 pathway activation. Furthermore, AMH co-treatment significantly reduced the incidence of DOX-induced labor dystocia, a complication of parturition, in pregnancies following chemotherapy treatment. These findings suggest that, in addition to ovarian protection, AMH may have benefits in preserving myometrial integrity and long-term uterine function following chemotherapy, further supporting its therapeutic potential for fertility preservation in cancer patients receiving chemotherapy.