• PMID: 24449892
• Gene Name: Trp73
• Condition: Required for spermatogenesis and male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Required for spermatogenesis and male infertility

TAp73 is required for spermatogenesis and the maintenance of male fertility

Inoue S, Tomasini R, Rufini A, Elia AJ, Agostini M, Amelio I, Cescon D, Dinsdale D, Zhou L, Harris IS, Lac S, Silvester J, Li WY, Sasaki M, Haight J, Brüstle A, Wakeham A, McKerlie C, Jurisicova A, Melino G, Mak TW.

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. FAU - Inoue, Satoshi AU - Inoue S AD - The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, ON, Canada M5G 2C1. FAU - Tomasini, Richard AU - Tomasini R FAU - Rufini, Alessandro AU - Rufini A FAU - Elia, Andrew J AU - Elia AJ FAU - Agostini, Massimiliano AU - Agostini M FAU - Amelio, Ivano AU - Amelio I FAU - Cescon, Dave AU - Cescon D FAU - Dinsdale, David AU - Dinsdale D FAU - Zhou, Lily AU - Zhou L FAU - Harris, Isaac S AU - Harris IS FAU - Lac, Sophie AU - Lac S FAU - Silvester, Jennifer AU - Silvester J FAU - Li, Wanda Y AU - Li WY FAU - Sasaki, Masato AU - Sasaki M FAU - Haight, Jillian AU - Haight J FAU - Brüstle, Anne AU - Brüstle A FAU - Wakeham, Andrew AU - Wakeham A FAU - McKerlie, Colin AU - McKerlie C FAU - Jurisicova, Andrea AU - Jurisicova A FAU - Melino, Gerry AU - Melino G