Sertoli cells require hnRNPC to support normal spermatogenesis and male fertility in mice

Author:

Mo Shaomei12,Shu Ge12,Cao Congcong12,Wang Mingxia12,Yang Jie12,Ye Jing12,Gui Yaoting12,Yuan Shuiqiao345,Ma Qian126

Affiliation:

1. Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics , Department of Urology, , Shenzhen, Guangdong , China

2. Peking University Shenzhen Hospital, the Fifth Clinical College of Anhui Medical University , Department of Urology, , Shenzhen, Guangdong , China

3. Institute of Reproductive Health , Tongji Medical College, , Wuhan , China

4. Huazhong University of Science and Technology , Tongji Medical College, , Wuhan , China

5. Laboratory Animal Center, Huazhong University of Science and Technology , Wuhan, Hubei , China

6. Institute of Urology, Shenzhen PKU-HKUST Medical Center , Shenzhen, Guangdong , China

Abstract

Abstract Sertoli cells act as highly polarized testicular cells that nutritionally support multiple stages of germ cell development. However, the gene regulation network in Sertoli cells for modulating germ cell development has yet to be fully understood. In this study, we report that heterogeneous nuclear ribonucleoproteins C in Sertoli cells are essential for germ cell development and male fertility. Conditional knockout of heterogeneous nuclear ribonucleoprotein C in mouse Sertoli cells leads to aberrant Sertoli cells proliferation, disrupted cytoskeleton of Sertoli cells, and compromised blood–testis barrier function, resulting in loss of supportive cell function and, ultimately, defective spermiogenesis in mice. Further ribonucleic acid-sequencing analyses revealed these phenotypes are likely caused by the dysregulated genes in heterogeneous nuclear ribonucleoprotein C–deficient Sertoli cells related to cell adhesion, cell proliferation, and apoptotic process. In conclusion, this study demonstrates that heterogeneous nuclear ribonucleoprotein C plays a critical role in Sertoli cells for maintaining the function of Sertoli cells and sustaining steady-state spermatogenesis in mice.

Funder

National Natural Science Foundation of China

Guangdong Foundation of Basic and Applied Basic Research

Shenzhen High-level Hospital Construction Fund

Medical Scientific Research Foundation of Guangdong Province

Publisher

Oxford University Press (OUP)

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