A Small Secreted Protein NICOL Regulates Lumicrine-mediated Sperm Maturation and Male Fertility

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Apr 24

PMID 37095084

Authors

Daiji Kiyozumi

Kentaro Shimada

Michael Chalick

Chihiro Emori

Mayo Kodani

Seiya Oura

Taichi Noda

Tsutomu Endo

Martin M Matzuk

Daniel H Wreschner

Masahito Ikawa

Affiliations

Soon will be listed here.

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.

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