HDAC3 promotes Sertoli cell maturation and maintains the blood–testis barrier dynamics

Author:

Liu Mengrou1ORCID,He Qing1ORCID,Yuan Zihan1ORCID,Chen Niuniu1ORCID,Ren Sen1ORCID,Du Qian1ORCID,Wang Yanfeng1ORCID,Han Shenglin1ORCID,Xu Chen1ORCID,Lu Luyang1ORCID,Sun Zheng2ORCID,Guan Yongjuan3ORCID,Xie Jie1ORCID,Guan Yichun4ORCID,Ye Lan1ORCID

Affiliation:

1. State Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University Nanjing China

2. Department of Medicine Baylor College of Medicine Houston Texas USA

3. College of Life Sciences, Capital Normal University Beijing China

4. Center for Reproductive Medicine the Third Affiliated Hospital of Zhengzhou University Zhengzhou China

Abstract

AbstractGerm cell development depends on the capacity of somatic Sertoli cells to undergo differentiation into a mature state and establish a germ cell‐specific blood–testis barrier (BTB). The BTB structure confers an immunological barrier for meiotic and postmeiotic germ cells, and its dynamic permeability facilitates a transient movement of preleptotene spermatocytes through BTB to enter meiosis. However, the regulatory factors involved in Sertoli cell maturation and how BTB dynamics coordinate germ cell development remain unclear. Here, we found a histone deacetylase HDAC3 abundantly expresses in Sertoli cells and localizes in both cytoplasm and nucleus. Sertoli cell‐specific Hdac3 knockout in mice causes infertility with compromised integrity of blood–testis barrier, leading to germ cells unable to traverse through BTB and an accumulation of preleptotene spermatocytes in juvenile testis. Mechanistically, nuclear HDAC3 regulates the expression program of Sertoli cell maturation genes, and cytoplasmic HDAC3 forms a complex with the gap junction protein Connexin 43 to modulate the BTB integrity and dynamics through regulating the distribution of tight junction proteins. Our findings identify HDAC3 as a critical regulator in promoting Sertoli cell maturation and maintaining the homeostasis of the blood–testis barrier.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

Publisher

Wiley

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