TAp73 is required for spermatogenesis and the maintenance of male fertility

Satoshi Inoue, Richard Tomasini, Alessandro Rufini, Andrew J. Elia, Massimiliano Agostini, Ivano Amelio, Dave Cescon, David Dinsdale, Lily Zhou, Isaac S. Harris, Sophie Lac, Jennifer Silvester, Wanda Y. Li, Masato Sasaki, Jillian Haight, Anne Brüstle, Andrew Wakeham, Colin McKerlie, Andrea Jurisicova, Gerry MelinoTak W. Mak

Research output: Contribution to journalArticlepeer-review

Abstract

The generation of viable sperm proceeds through a series of coordinated steps, including germ cell self-renewal, meiotic recombination, and terminal differentiation into functional spermatozoa. The p53 family of transcription factors, including p53, p63, and p73, are critical for many physiological processes, including female fertility, but little is known about their functions in spermatogenesis. Here, we report that deficiency of the TAp73 isoform, but not p53 or ΔNp73, results in male infertility because of severe impairment of spermatogenesis. Mice lacking TAp73 exhibited increased DNA damage and cell death in spermatogonia, disorganized apical ectoplasmic specialization, malformed spermatids, and marked hyperspermia. We demonstrated that TAp73 regulates the mRNA levels of crucial genes involved in germ stem/ progenitor cells (CDKN2B), spermatid maturation/spermiogenesis (metalloproteinase and serine proteinase inhibitors), and steroidogenesis (CYP21A2 and progesterone receptor). These alterations of testicular histology and gene expression patterns were specific to TAp73 null mice and not features of mice lacking p53. Our work provides previously unidentified in vivo evidence that TAp73 has a unique role in spermatogenesis that ensures the maintenance of mitotic cells and normal spermiogenesis. These results may have implications for the diagnosis and management of human male infertility.

Original languageEnglish
Pages (from-to)1843-1848
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number5
DOIs
Publication statusPublished - Feb 4 2014

Keywords

  • ADAM17
  • MMP13
  • Serpin
  • Timp

ASJC Scopus subject areas

  • General

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