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.

Development (Cambridge, England)
|March 28, 2013
PubMed

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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