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

Anti-Müllerian hormone (AMH) has emerged as a potential fertoprotective agent, demonstrating its strongest protective effects against Doxorubicin (DOX)-induced ovarian toxicity. While chemotherapy's gonadotoxic impact on ovaries has been extensively studied, its effects on the uterus remain poorly understood. In this study, we investigated DOX-induced uterine damage and assessed the protective role of AMH co-treatment. DOX triggered DNA double-strand breaks in the uterine myometrium, activating Cdkn1a and other Tp53 pathway genes, and was linked to increased dystocia in pregnant mice. AMH co-treatment counteracted these effects by reducing ?-H2AX-positive DNA damage foci, suppressing Tp53 pathway activation, and improving pregnancy outcomes. These findings establish AMH as a promising therapeutic agent for preserving uterine integrity during chemotherapy, opening new avenues for fertility preservation and improved reproductive health in cancer patients. Overall design: To elucidate the impact of DOX and AMH on prepubertal uterine function, we administered two weekly doses of DOX (3mg/kg) to prepubertal mice (postnatal day 25). A comparative group received concurrent administration of AMH. Uteri were harvested at 4 and 24 hours post-treatment for bulk RNA sequencing analysis.