β-Defensin 19/119 mediates sperm chemotaxis and is associated with idiopathic infertility

Xiaofeng Li; Chun Yuan; Jianwu Shi; Hang Kang; Yufei Chen; Yonggang Duan; Jing Jin; Lai Ping Cheung; Tin Chiu Li; Ying Liu; Yugui Cui; Ye Chun Ruan; Xiaohua Jiang; Zhiming Cai; Hsiao Chang Chan; Ling Ji; Xuhui Zeng; Jiaying Liu; Hao Chen; Kin Lam Fok

doi:10.1016/j.xcrm.2022.100825

β-Defensin 19/119 mediates sperm chemotaxis and is associated with idiopathic infertility

Cell Rep Med. 2022 Dec 20;3(12):100825. doi: 10.1016/j.xcrm.2022.100825. Epub 2022 Dec 12.

Authors

Xiaofeng Li¹, Chun Yuan², Jianwu Shi³, Hang Kang³, Yufei Chen³, Yonggang Duan⁴, Jing Jin⁵, Lai Ping Cheung⁶, Tin Chiu Li⁶, Ying Liu², Yugui Cui², Ye Chun Ruan⁵, Xiaohua Jiang⁷, Zhiming Cai⁸, Hsiao Chang Chan⁹, Ling Ji¹⁰, Xuhui Zeng¹¹, Jiaying Liu¹², Hao Chen¹³, Kin Lam Fok¹⁴

Affiliations

¹ Department of Laboratory Medicine, Peking University Shenzhen Hospital, Lianhua Road No. 1120, Futian District, Shenzhen, PR China; Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
² State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, PR China.
³ Institute of Reproductive Medicine, Medical School of Nantong University, Nantong, PR China.
⁴ The University of Hong Kong-Shenzhen Hospital, Shenzhen, PR China.
⁵ Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
⁶ Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China.
⁷ Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China; School of Biomedical Sciences Core Laboratory, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, PR China.
⁸ Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, PR China.
⁹ Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China; School of Biomedical Sciences Core Laboratory, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, PR China; Sichuan University-The Chinese University of Hong Kong Joint Laboratory for Reproductive Medicine, West China Second University Hospital, Chengdu, PR China.
¹⁰ Department of Laboratory Medicine, Peking University Shenzhen Hospital, Lianhua Road No. 1120, Futian District, Shenzhen, PR China.
¹¹ Institute of Reproductive Medicine, Medical School of Nantong University, Nantong, PR China. Electronic address: zengxuhui@ntu.edu.cn.
¹² State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, PR China. Electronic address: jyliu_nj@126.com.
¹³ Institute of Reproductive Medicine, Medical School of Nantong University, Nantong, PR China. Electronic address: chenhao@ntu.edu.cn.
¹⁴ Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China; School of Biomedical Sciences Core Laboratory, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, PR China; Sichuan University-The Chinese University of Hong Kong Joint Laboratory for Reproductive Medicine, West China Second University Hospital, Chengdu, PR China. Electronic address: ellisfok@cuhk.edu.hk.

Abstract

Sperm chemotaxis is required for guiding sperm toward the egg. However, the molecular identity of physiological chemoattractant and its involvement in infertility remain elusive. Here, we identify DEFB19/119 (mouse/human orthologs) as a physiological sperm chemoattractant. The epithelia of the female reproductive tract and the cumulus-oocyte complex secrete DEFB19/119 that elicits calcium mobilization via the CatSper channel and induces sperm chemotaxis in capacitated sperm. Manipulating the level of DEFB19 in mice determines the number of sperm arriving at the fertilization site. Importantly, we identify exon mutations in the DEFB119 gene in idiopathic infertile women with low level of DEFB119 in the follicular fluid. The level of DEFB119 correlates with the chemotactic potency of follicular fluid and predicts the infertile outcome with positive correlation. This study reveals the pivotal role of DEFB19/119 in sperm chemotaxis and demonstrates its potential application in the diagnosis of idiopathic infertility.

Keywords: DEFB119; DEFB19; idiopathic infertility; sperm chemotaxis; β-defensin.

Publication types

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

MeSH terms

Animals
Chemotactic Factors / metabolism
Chemotaxis / physiology
Female
Humans
Infertility, Female*
Male
Mice
Semen / metabolism
Spermatozoa / metabolism
beta-Defensins*

Substances

beta-Defensins
Chemotactic Factors