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Rreb1 is a key transcription factor in Sertoli cell maturation and function and spermatogenesis in mouse

Published online by Cambridge University Press:  22 January 2024

Zhu Wu
Affiliation:
Department of Histology and Embryology, School of Basic Medical Sciences, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
Xu Chen
Affiliation:
Department of Histology and Embryology, School of Basic Medical Sciences, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
Tong Yan
Affiliation:
Department of Histology and Embryology, School of Basic Medical Sciences, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
Li Yu
Affiliation:
Department of Histology and Embryology, School of Basic Medical Sciences, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
Longsheng Zhang
Affiliation:
Department of Histology and Embryology, School of Basic Medical Sciences, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
Meimei Zheng
Affiliation:
Reproductive Medicine Center of No. 960 Hospital of PLA, Jinan, China
Hui Zhu*
Affiliation:
Department of Histology and Embryology, School of Basic Medical Sciences, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China
*
Corresponding author: Hui Zhu; Email: njzhuhui@njmu.edu.cn

Summary

Spermatogenesis is a developmental process driven by interactions between germ cells and Sertoli cells. This process depends on appropriate gene expression, which might be regulated by transcription factors. This study focused on Rreb1, a zinc finger transcription factor, and explored its function and molecular mechanisms in spermatogenesis in a mouse model. Our results showed that RREB1 was predominantly expressed in the Sertoli cells of the testis. The decreased expression of RREB1 following injection of siRNA caused impaired Sertoli cell development, which was characterized using a defective blood–testis barrier structure and decreased expression of Sertoli cell functional maturity markers; its essential trigger might be SMAD3 destabilization. The decreased expression of RREB1 in mature Sertoli cells influenced the cell structure and function, which resulted in abnormal spermatogenesis, manifested as oligoasthenoteratozoospermia, and we believe RREB1 plays this role by regulating the transcription of Fshr and Wt1. RREB1 has been reported to activate Fshr transcription, and we demonstrated that the knockdown of Rreb1 caused a reduction in follicle-stimulating hormone receptor (FSHR) in the testis, which could be the cause of the increased sperm malformation. Furthermore, we confirmed that RREB1 directly activates Wt1 promoter activity, and RREB1 downregulation induced the decreased expression of Wt1 and its downstream polarity-associated genes Par6b and E-cadherin, which caused increased germ-cell death and reduced sperm number and motility. In conclusion, RREB1 is a key transcription factor essential for Sertoli cell development and function and is required for normal spermatogenesis.

Type
Research Article
Copyright
© The Author(s), 2024. Published by Cambridge University Press

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