BRG1 Is Dispensable for Sertoli Cell Development and Functions in Mice.

Shuai Wang,Pengxiang Wang,Dongli Liang,Yuan Wang

doi:10.3390/ijms21124358

Shuai Wang, Pengxiang Wang + Show 2 more

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https://doi.org/10.3390/ijms21124358

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Abstract

Sertoli cells are somatic supporting cells in spermatogenic niche and play critical roles in germ cell development, but it is yet to be understood how epigenetic modifiers regulate Sertoli cell development and contribution to spermatogenesis. BRG1 (Brahma related gene 1) is a catalytic subunit of the mammalian SWI/SNF chromatin remodeling complex and participates in transcriptional regulation. The present study aimed to define the functions of BRG1 in mouse Sertoli cells during mouse spermatogenesis. We found that BRG1 protein was localized in the nuclei of both Sertoli cells and germ cells in seminiferous tubules. We further examined the requirement of BRG1 in Sertoli cell development using a Brg1 conditional knockout mouse model and two Amh-Cre mouse strains to specifically delete Brg1 gene from Sertoli cells. We found that the Amh-Cre mice from Jackson Laboratory had inefficient recombinase activities in Sertoli cells, while the other Amh-Cre strain from the European Mouse Mutant Archive achieved complete Brg1 deletion in Sertoli cells. Nevertheless, the conditional knockout of Brg1 from Sertoli cells by neither of Amh-Cre strains led to any detectable abnormalities in the development of either Sertoli cells or germ cells, suggesting that BRG1-SWI/SNF complex is dispensable to the functions of Sertoli cells in spermatogenesis.

Highlights

IntroductionHaploid spermatozoa are continuously produced from spermatogonial stem cells (SSCs)
During mammalian spermatogenesis, haploid spermatozoa are continuously produced from spermatogonial stem cells (SSCs)
Given the direct physical interaction of Sertoli cells with germ cells in seminiferous tubules, alteration in their number and/or function usually leads to defects in spermatogenesis [4,17,33]

Summary

Introduction

Haploid spermatozoa are continuously produced from spermatogonial stem cells (SSCs). This process requires a tightly regulated interplay between germ cells and various somatic supporting cells in the spermatogenic niche. Of these supporting cell types, Leydig cells, peritubular myoid cells, fibroblasts, and macrophages all locate at interstitium or immediately outside the seminiferous tubules. Immature Sertoli cells continue to proliferate until 12–17 days post-partum (dpp). Afterwards, Sertoli cells exit from cell cycle and enter a differentiation process which includes a cessation of proliferation, alterations in transcription and protein expression, and functional maturation [6,7]

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