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作者

Zongzhuang Wen Haixia Zhu Jing Wang Bin Wu Aizhen Zhang Hui Zhao Chenyang Song Shuangyuan Liu Yin Cheng Hongxiang Wang Jianyuan Li Daqing Sun Xiaolong Fu Jiangang Gao Min Liu

作者单位

²School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan 250100, PR China ⁶Department of Pediatric Surgery, Tianjin Medical University General Hospital, Tianjin 300041, PR China ⁵Key Laboratory of Male Reproductive Health, Institute of Science and Technology, National Health Commission, Beijing 100081, PR China ³Department of Basic Medicine, Jinan Vacational College of Nursing, Jinan 250102, PR China ⁴Department of Reproductive Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250100, PR China ¹Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan 250117, PR China

刊名

Life Sciences

年份

2022

页码

121319

ISSN

0024-3205

关键词

HSPA5 Spermatogenesis Spermatogonia Male infertility

摘要

Heat shock proteins have important roles in different developmental stages of spermatogenesis. The heat shock 70 kDa protein 5 is an important component of the unfolded protein response that promotes cell survival under endoplasmic reticulum stress conditions. In this study, we explored the function of HSPA5 in spermatogenesis, by generating a germ cell-specific deletion mutant of the Hspa5 gene using CRISPR/Cas9 technology and the Cre/Loxp system. Hspa5 knockout resulted in severe germ cell...更多

Heat shock proteins have important roles in different developmental stages of spermatogenesis. The heat shock 70 kDa protein 5 is an important component of the unfolded protein response that promotes cell survival under endoplasmic reticulum stress conditions. In this study, we explored the function of HSPA5 in spermatogenesis, by generating a germ cell-specific deletion mutant of the Hspa5 gene using CRISPR/Cas9 technology and the Cre/Loxp system. Hspa5 knockout resulted in severe germ cell loss and vacuolar degeneration of seminiferous tubules, leading to complete arrest of spermatogenesis, testicular atrophy, and male infertility in adult mice. Furthermore, defects occurred in the spermatogenic epithelium of Hspa5-cKO mice as early as Cre recombinase expression. Germ cell ablation of Hspa5 impaired spermatogonia proliferation and differentiation from post-natal day 7 to P10, which led to a dramatic reduction of differentiated spermatogonia, compromised meiosis, and led to impairment of testis development and the disruption of the first wave of spermatogenesis. Consistent with these results, single-cell RNA sequencing analysis showed that germ cells, especially differentiated spermatogonia, were dramatically reduced in Hspa5-cKO testes compared with controls at P10, further confirming that HSPA5 is crucial for germ cell development. These results suggest that HSPA5 is indispensable for normal spermatogenesis and male reproduction in mice.收起

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