Publication Date
4-24-2023
Journal
Nature Communications
DOI
10.1038/s41467-023-37984-x
PMID
37095084
PMCID
PMC10125973
PubMedCentral® Posted Date
4-24-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Male, Mice, Animals, Sperm Maturation, Semen, Testis, Epididymis, Spermatozoa, Fertility, Mammals, Spermatogenesis, Extracellular signalling molecules, Reproductive biology
Abstract
The mammalian spermatozoa produced in the testis require functional maturation in the epididymis for their full competence. Epididymal sperm maturation is regulated by lumicrine signalling pathways in which testis-derived secreted signals relocate to the epididymis lumen and promote functional differentiation. However, the detailed mechanisms of lumicrine regulation are unclear. Herein, we demonstrate that a small secreted protein, NELL2-interacting cofactor for lumicrine signalling (NICOL), plays a crucial role in lumicrine signalling in mice. NICOL is expressed in male reproductive organs, including the testis, and forms a complex with the testis-secreted protein NELL2, which is transported transluminally from the testis to the epididymis. Males lacking Nicol are sterile due to impaired NELL2-mediated lumicrine signalling, leading to defective epididymal differentiation and deficient sperm maturation but can be restored by NICOL expression in testicular germ cells. Our results demonstrate how lumicrine signalling regulates epididymal function for successful sperm maturation and male fertility.
Included in
Biological Phenomena, Cell Phenomena, and Immunity Commons, Biomedical Informatics Commons, Genetics and Genomics Commons, Medical Genetics Commons, Medical Molecular Biology Commons, Medical Specialties Commons