Cathepsin B plays a role in spermatogenesis and sperm maturation through regulating autophagy and apoptosis in mice

Zongzhuang Wen; Haixia Zhu; Bin Wu; Aizhen Zhang; Hongxiang Wang; Yin Cheng; Hui Zhao; Jianyuan Li; Min Liu; Jiangang Gao

doi:10.7717/peerj.14472

Cathepsin B plays a role in spermatogenesis and sperm maturation through regulating autophagy and apoptosis in mice

PeerJ. 2022 Dec 2:10:e14472. doi: 10.7717/peerj.14472. eCollection 2022.

Authors

Zongzhuang Wen^#¹, Haixia Zhu^#², Bin Wu³, Aizhen Zhang³, Hongxiang Wang², Yin Cheng², Hui Zhao¹, Jianyuan Li⁴, Min Liu¹, Jiangang Gao^{1

2}

Affiliations

¹ Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, China.
² School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan, China.
³ Department of Reproductive Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
⁴ Key Laboratory of Male Reproductive Health, Institute of Science and Technology, National Health Commission, Beijing, China.

^# Contributed equally.

Abstract

Spermatogenesis and sperm maturation are complex and highly ordered biological processes. Any failure or disorder in these processes can cause defects in sperm morphology, motility, and fertilization ability. Cathepsin B (CTSB) is involved in the regulation of a variety of pathological processes. In the present study, we found that CTSB was abundantly expressed in the male reproductive system, however, the specific role of CTSB in regulating spermatogenesis and sperm maturation remained elusive. Hence, we generated Ctsb ^-/- mice using CRISPR/Cas9 technology. In Ctsb ^-/- mice, sperm count was significantly decreased while the level of morphologically abnormal sperm was markedly increased. Additionally, these mice had significantly lower levels of progressive motility sperm and elevated levels of immobilized sperm. Histological analysis showed slight vacuolization in the testis epithelium, as well as the loss of epididymal epithelium cells. Further investigation showed that autophagic activity was inhibited and apoptotic activity was increased in both the testis and epididymis of Ctsb ^-/- mice. Together, our findings demonstrate that CTSB plays an important role in spermatogenesis and sperm maturation in mice.

Keywords: CRISPR/Cas9; CTSB; Sperm maturation; Spermatogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis
Cathepsin B* / genetics
Cathepsin B* / metabolism
Male
Mice
Semen
Sperm Maturation
Spermatogenesis*

Substances

Cathepsin B

Grants and funding

This work was supported by the National Key Research and Developmental Program of China (Grant No. 2018YFC1003602). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.