NOTCH1 Gain of Function in Germ Cells Causes Failure of Spermatogenesis in Male Mice

Authors

Zaohua Huang, Department of Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Miami, FloridaFollow
Bryan Rivas, Department of Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida
Alexander I. Agoulnik, Department of Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida; Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TexasFollow

Date of this Version

7-30-2013

Document Type

Article

Abstract

NOTCH1 is a member of the NOTCH receptor family, a group of single-pass trans-membrane receptors. NOTCH signaling is highly conserved in evolution and mediates communication between adjacent cells. NOTCH receptors have been implicated in cell fate determination, as well as maintenance and differentiation of stem cells. In the mammalian testis expression of NOTCH1 in somatic and germ cells has been demonstrated, however its role in spermatogenesis was not clear. To study the significance of NOTCH1 in germ cells, we applied a cre/loxP approach in mice to induce NOTCH1 gain- or loss-of function specifically in male germ cells. Using a Stra8-icretransgene we produced mice with conditional activation of the NOTCH1 intracellular domain (NICD) in germ cells. Spermatogenesis in these mutants was progressively affected with age, resulting in decreased testis weight and sperm count. Analysis of downstream target genes of NOTCH1 signaling showed an increased expression of Hes5, with a reduction of the spermatogonial differentiation marker, Neurog3 expression in the mutant testis. Apoptosis was significantly increased in mouse germ cells with the corresponding elevation of pro-apoptotic Trp53 and Trp63genes' expression. We also showed that the conditional germ cell-specific ablation of Notch1 had no effect on spermatogenesis or male fertility. Our data suggest the importance of NOTCH signaling regulation in male germ cells for their survival and differentiation.

Comments

This article was originally published in PLoS One.

Identifier

FIDC001527

Recommended Citation

Huang Z, Rivas B, Agoulnik AI (2013) NOTCH1 Gain of Function in Germ Cells Causes Failure of Spermatogenesis in Male Mice. PLoS ONE 8(7): e71213. doi:10.1371/journal.pone.0071213

Creative Commons License

This work is licensed under a Creative Commons Attribution 3.0 License.