AMH protects the ovary from doxorubicin by regulating cell fate and the response to DNA damage

• DOI: 10.1073/pnas.2414734122
• Publication Date: 2025-01-28T18:40:11Z
• Authors: Ngoc Minh Phuong ...; Eun Mi Chang; Maeva Chauvin; Natalie Sicher; Aki Kashiwagi; Nicholas Nagykery; Christina Chow; Phoebe May; Alana Mermin-Bunnell; Josephine Cleverdon; Thy Duong; Motohiro Kano; Philippe Godin; Marie-Charlotte M...; Dadi Gao; Patricia K. Donahoe; David Pepin
• Keywords: Anti-Müllerian hormone; SOX9

Anti-Müllerian hormone (AMH) protects the ovarian reserve from chemotherapy, and this effect is most pronounced with Doxorubicin (DOX). However, DOX toxicity AMH rescue mechanisms in ovary have remained unclear. Herein, we characterize consequences of these treatments cell types using scRNAseq. DOX-induced DNA damage activates Tp53 class mediators across types. In mesenchyme, cotreatment halts theca progenitor differentiation reduces apoptotic gene expression. preantral granulosa cells, upregulates cycle inhibitor Cdkn1a dysregulates Wnt signaling, which are ameliorated by cotreatment. Finally, induces Id3 , a involved repair, necessary to prevent accumulation lesions marked γ-H2AX. Altogether protection contribute sustained fertility mice, offering promising broad avenues for preservation cancer patients undergoing chemotherapy.