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TAp73 is required for spermatogenesis and the maintenance of male fertility.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2014 Feb 04; Vol. 111 (5), pp. 1843-8. Date of Electronic Publication: 2014 Jan 21. - Publication Year :
- 2014
-
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.
- Subjects :
- ADAM Proteins genetics
ADAM Proteins metabolism
ADAM17 Protein
Aging pathology
Animals
Apoptosis genetics
Cell Count
Cell Proliferation
DNA Damage genetics
DNA-Binding Proteins deficiency
Female
Gene Expression Regulation
Humans
Infertility, Male blood
Infertility, Male genetics
Infertility, Male pathology
Male
Matrix Metalloproteinase 13 genetics
Matrix Metalloproteinase 13 metabolism
Mice
Mice, Knockout
Nuclear Proteins deficiency
Oxidative Stress genetics
Progesterone blood
RNA, Messenger genetics
RNA, Messenger metabolism
Spermatozoa metabolism
Spermatozoa pathology
Testis metabolism
Testis pathology
Tumor Protein p73
Tumor Suppressor Proteins deficiency
DNA-Binding Proteins metabolism
Fertility genetics
Nuclear Proteins metabolism
Spermatogenesis genetics
Tumor Suppressor Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 111
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 24449892
- Full Text :
- https://doi.org/10.1073/pnas.1323416111