DNA damage-induced primordial follicle oocyte apoptosis and loss of fertility require TAp63-mediated induction of Puma and Noxa

Jeffery B Kerr, Karla J Hutt, Ewa M Michalak, Michele Cook, Cassandra Vandenberg, Seng H Liew, Philippe Bouillet, Alea A Mills, Clare L Scott, Jock K Findlay, Andreas Strasser

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139 Citations (Scopus)

Abstract

Trp63, a transcription factor related to the tumor suppressor p53, is activated by diverse stimuli and can initiate a range of cellular responses. TAp63 is the predominant Trp53 family member in primordial follicle oocyte nuclei and is essential for their apoptosis triggered by DNA damage in vivo. After gamma-irradiation, induction of the proapoptotic BH3-only members Puma and Noxa was observed in primordial follicle oocytes from WT and Trp53(-/-) mice but not in those from TAp63-deficient mice. Primordial follicle oocytes from mice lacking Puma or both Puma and Noxa were protected from gamma-irradiation-induced apoptosis and, remarkably, could produce healthy offspring. Hence, PUMA and NOXA are critical for DNA damage-induced, TAp63-mediated primordial follicle oocyte apoptosis. Thus, blockade of PUMA may protect fertility during cancer therapy and prevent premature menopause, improving women s health.
Original languageEnglish
Pages (from-to)343 - 352
Number of pages10
JournalMolecular Cell
Volume48
Issue number3
DOIs
Publication statusPublished - 2012

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