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Updated: May 12, 2026

A Seminiferous Tubule Squash Technique for the Cytological Analysis of Spermatogenesis Using the Mouse Model
Published on: February 6, 2018
Lgr4-mediated Wnt/β-catenin signaling in peritubular myoid cells is essential for spermatogenesis
Yu Qian1, Shijie Liu, Yuting Guan
1Institute of Biomedical Sciences, East China Normal University, Shanghai, China.
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.
Insights
Leucine-rich repeat-containing G protein-coupled receptor 4 (Lgr4) is crucial for male fertility. Loss of Lgr4 in peritubular myoid cells disrupts spermatogenesis by affecting Wnt/β-catenin signaling.
Area of Science:
- Reproductive biology
- Cell signaling
- Molecular endocrinology
Background:
- Peritubular myoid cells (PMCs) are vital for male fertility, but their role in spermatogenesis and associated signaling pathways remain unclear.
- Understanding the molecular mechanisms governing PMC function is essential for addressing male infertility.
Purpose of the Study:
- To investigate the role of Leucine-rich repeat-containing G protein-coupled receptor 4 (Lgr4) in peritubular myoid cells (PMCs) and its impact on spermatogenesis.
- To elucidate the signaling pathways regulated by Lgr4 in PMCs.
Main Methods:
- Utilized Lgr4 knockout mouse models to study PMC function and spermatogenesis.
- Analyzed gene and protein expression, including androgen receptor, alpha-smooth muscle actin, and extracellular matrix proteins.
- Investigated Wnt/β-catenin signaling pathway activation and modulation.
- Employed genetic and pharmacological interventions to rescue Lgr4 deficiency phenotypes.
Main Results:
- Lgr4 is selectively expressed in mouse testicular PMCs.
- Loss of Lgr4 in PMCs leads to meiotic arrest and apoptosis of germ cells.
- Lgr4 deficiency reduces key PMC markers and impairs Sertoli cell function.
- Wnt/β-catenin signaling is attenuated in Lgr4-deficient PMCs.
- Partial rescue of testicular phenotype was observed upon Wnt/β-catenin pathway reactivation.
Conclusions:
- Lgr4 signaling in PMCs, mediated by the Wnt/β-catenin pathway, is essential for regulating PMC function and maintaining spermatogenesis.
- Lgr4 is a critical regulator of male fertility at the molecular level.
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