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WDR62 is required for centriole duplication in spermatogenesis and manchette removal in spermiogenesis

Uda Y Ho1, Chun-Wei Allen Feng2, Yvonne Y Yeap2

  • 1School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia. u.ho@uq.edu.au.

Communications Biology
|June 1, 2021
PubMed

Insights

WD repeat domain 62 (WDR62) deficiency impairs male fertility by causing centriole underduplication and defects in spermatid development. This leads to sperm with abnormal morphology and reduced motility, mimicking human subfertility.

Area of Science:

  • Cell Biology
  • Reproductive Biology
  • Genetics

Background:

  • WD repeat domain 62 (WDR62) is a crucial scaffold protein regulating centriole duplication and mitotic spindle assembly.
  • WDR62 mutations are linked to primary microcephaly and premature ovarian insufficiency in humans.
  • The role of WDR62 in male meiosis and spermatogenesis remains largely unexplored.

Purpose of the Study:

  • To investigate the function of WDR62 during male meiosis and spermatogenesis using a genetrap mouse model.
  • To characterize the impact of WDR62 deficiency on centriole duplication, spindle assembly, and sperm development.

Main Methods:

  • Generation of a WDR62-deficient genetrap mouse model.
  • Analysis of spermatocyte and spermatid development using microscopy and molecular markers.
  • Assessment of centriole duplication, spindle organization, and sperm morphology.

Main Results:

  • WDR62 deficiency caused centriole underduplication in spermatocytes due to reduced CEP63 accumulation.
  • This led to prolonged metaphase, increased apoptosis, and defects in spermiogenesis, including delayed manchette removal.
  • WDR62-deficient mice exhibited oligoasthenoteratospermia, characterized by low sperm count, poor motility, and abnormal morphology.

Conclusions:

  • WDR62 is essential for proper centriole duplication and timely progression of spermatogenesis and spermiogenesis.
  • WDR62 deficiency results in male subfertility phenotypes resembling human oligoasthenoteratospermia.
  • These findings highlight WDR62's critical role in male reproductive health.

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