Anti-Müllerian hormone ameliorates uterine DNA damage response and prevents pregnancy complications in doxorubicin-treated mice

Anti-Müllerian hormone is a promising fertoprotective agent, demonstrating particularly strong efficacy against doxorubicin-induced ovarian toxicity. However, the impact of chemotherapy on the uterus, and the potential benefits of anti-Müllerian hormone in this context, remain poorly understood. In this study, we characterized doxorubicin-induced uterine damage and assessed the fertoprotective effect of anti-Müllerian hormone co-treatment in mice. Acutely, doxorubicin 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 the mRNA and protein levels. Anti-Müllerian hormone co-treatment counteracted these effects by reducing γ-H2AX-positive DNA damage lesion accumulation and by suppressing Trp53 and its downstream pathway. Furthermore, anti-Müllerian hormone co-treatment significantly reduced the incidence of doxorubicin-induced labor dystocia, a complication of parturition, in pregnancies following chemotherapy treatment. These findings suggest that, in addition to ovarian protection, anti-Müllerian hormone 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.