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

• Published in: Cell reports. Medicine 2022-12, Vol.3 (12), p.100825-100825, Article 100825
• Main Authors: Li, Xiaofeng, Yuan, Chun, Shi, Jianwu, Kang, Hang, Chen, Yufei, Duan, Yonggang, Jin, Jing, Cheung, Lai Ping, Li, Tin Chiu, Liu, Ying, Cui, Yugui, Ruan, Ye Chun, Jiang, Xiaohua, Cai, Zhiming, Chan, Hsiao Chang, Ji, Ling, Zeng, Xuhui, Liu, Jiaying, Chen, Hao, Fok, Kin Lam
• Format: Article
• Language: English
• Subjects: Animals; beta-Defensins; Chemotactic Factors - metabolism; Chemotaxis - physiology; DEFB119; DEFB19; Female; Humans; idiopathic infertility; Infertility, Female; Male; Mice; Semen - metabolism; sperm chemotaxis; Spermatozoa - metabolism; β-defensin
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2022.100825

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. [Display omitted] •DEFB119/DEFB19 are physiological chemoattractants for sperm chemotaxis in human and mouse•DEFB19 mediates multistage chemotaxis along the female reproductive tract•DEFB119 gene mutations are associated with idiopathic infertility in women Li et al. describe the multistage chemotaxis in the female reproductive tract that guides the sperm to the fertilization site and the oocyte by the physiological chemoattractant DEFB19/119. Mutations in DEFB119 gene may underlie unexplained infertility in women.