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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE289996 | GEO | 2025/08/31

REPOSITORIES: GEO

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

Project description: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.

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Expression data from anti-müllerian hormone treated preantral/small antral mouse ovary follicles

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Chemotherapeutic agent doxorubicin alters uterine gene expression in response to estrogen in ovariectomized CD-1 adult mice

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Expression data from anti-müllerian hormone treated preantral/small antral mouse ovary follicles

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