title: Lgr4-mediated Wnt/β-catenin signaling in peritubular myoid cells is essential for spermatogenesis.
abstract: Peritubular myoid cells (PMCs) are myofibroblast-like cells that surround the seminiferous tubules and play essential roles in male fertility. How these cells modulate spermatogenesis and the signaling pathways that are involved are largely unknown. Here we report that Lgr4 is selectively expressed in mouse PMCs in the testes, and loss of Lgr4 leads to germ cells arresting at meiosis I and then undergoing apoptosis. In PMCs of Lgr4 mutant mice, the expression of androgen receptor, alpha-smooth muscle actin and extracellular matrix proteins was dramatically reduced. Malfunctioning PMCs further affected Sertoli cell nuclear localization and functional protein expression in Lgr4(-/-) mice. In addition, Wnt/β-catenin signaling was activated in wild-type PMCs but attenuated in those of Lgr4(-/-) mice. When Wnt/β-catenin signaling was reactivated by crossing with Apc(min/+) mice or by Gsk3β inhibitor treatment, the Lgr4 deficiency phenotype in testis was partially rescued. Together, these data demonstrate that Lgr4 signaling through Wnt/β-catenin regulates PMCs and is essential for spermatogenesis.
authors.affiliation: Institute of Biomedical Sciences, East China Normal University, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qian
authors.forename: Shijie
authors.initials: S
authors.lastname: Liu
authors.forename: Yuting
authors.initials: Y
authors.lastname: Guan
authors.forename: Hongjie
authors.initials: H
authors.lastname: Pan
authors.forename: Xin
authors.initials: X
authors.lastname: Guan
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Qiu
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.forename: Na
authors.initials: N
authors.lastname: Gao
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.forename: Dali
authors.initials: D
authors.lastname: Li
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013091:Spermatogenesis / Q000502:physiology*; D013737:Testis / Q000166:cytology*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*; D001616:beta-Galactosidase
chemical_list: C496200:LGR4 protein, mouse; D043562:Receptors, G-Protein-Coupled; D051176:beta Catenin; D001616:beta-Galactosidase; D001973:Bromodeoxyuridine