Journal article

Loss of PUMA protects the ovarian reserve during DNA-damaging chemotherapy and preserves fertility

Nguyen Quynh-Nhu, Nadeen Zerafa, Seng H Liew, F Hamish Morgan, Andreas Strasser, Clare L Scott, Jock K Findlay, Martha Hickey, Karla J Hutt



Female gametes are stored in the ovary in structures called primordial follicles, the supply of which is non-renewable. It is well established that DNA-damaging cancer treatments can deplete the ovarian reserve of primordial follicles, causing premature ovarian failure and infertility. The precise mechanisms underlying this chemotherapy-driven follicle loss are unclear, and this has limited the development of targeted ovarian-protective agents. To address this fundamental knowledge gap, we used gene deletion mouse models to examine the role of the DNA damage-induced pro-apoptotic protein, PUMA, and its transcriptional activator TAp63, in primordial follicle depletion caused by treatment with..

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Awarded by National Health and Medical Research Council Australia

Awarded by Leukemia and Lymphoma Society Specialized Center of Research Program Grant

Awarded by Cancer Council Victoria

Awarded by National Breast Cancer Foundation

Funding Acknowledgements

This work was supported by fellowships and grants from the National Health and Medical Research Council Australia (Project Grant #1007027, Program Grant #1016701, and Fellowships KJH (#1050130), AS (#1020363)); the Leukemia and Lymphoma Society Specialized Center of Research Program Grant (#7001-13); and the Cancer Council Victoria Grant in Aid (#1052309); National Breast Cancer Foundation (#NC14-001). This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. The authors acknowledge the facilities, scientific, and technical assistance of Monash Micro Imaging, the Monash Animal Research Platform, and the Monash Histology Platform, Monash University, Victoria, Australia. The authors thank Dr Dagmar Wilhelm, The University of Melbourne, for supplying the rabbit anti-FOXL2 antibody used in this study.