Anti-Müllerian Hormone Reduces Uterine DNA Damage and Pregnancy Complications in Doxorubicin-Treated Mice [RNA-seq]

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 γ-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. 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.