Testis-secreted factor Ts-1 is indispensable for lumicrine-mediated regulation of male fertility. (September 2022)

• Record Type: Journal Article
• Authors: Kiyozumi, Daiji; Shimada, Kentaro; Wreschner, Daniel; Ikawa, Masahito
• Is Part Of: Journal of reproductive immunology. Volume 153(2022)
• Publication Date: 2022-09
• Subjects: Reproduction -- Immunological aspects -- Periodicals; Immunology -- Periodicals; Allergy and Immunology -- Periodicals; Reproduction -- Periodicals; Reproduction -- Immunologie -- Périodiques; Immunologie -- Périodiques; Immunology; Reproduction -- Immunological aspects; Periodicals; Electronic journals; Electronic journals; 615.766
• DOI: 10.1016/j.jri.2022.103720
• Languages: English
• ISSNs: 0165-0378

Abstract

Abstract : Lumicrine is a signaling mechanism in which testis-derived secreted factor act on epididymis through luminal channel to regulate epididymal function indispensable for sperm maturation. We previously identified an ECM-like molecule NELL2 as a lumicrine factor. NELL2 functions as a ligand for receptor tyrosine kinase ROS1 expressed in epididymis, and Nell2 KO male mice are infertile because of impaired epididymal differentiation and subsequent sperm maturation. Here we investigated a novel testes-derived secreted factor Ts-1. Ts-1 KO mice possessed male infertility because of impaired epididymal differentiation and aberrant sperm maturation, and phenocopied Nell2 KO mice. The male infertility of Ts-1 KO mice was rescued when Ts-1 was specifically expressed by introducing transgene in Ts-1 KO genetic background. We also found that Ts-1 bound to NELL2 by using recombinant proteins in vitro. These findings suggest a possibility that Ts-1 regulates male fertility by modulating NELL2 function.