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Male infertility in mice lacking the store-operated Ca(2+) channel Orai1

Felicity M Davis1, Eugenia H Goulding2, Diane M D'Agostin1

  • 1Signal Transduction Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.

Cell Calcium
|March 13, 2016
PubMed

Insights

Store-operated calcium entry (SOCE) channels, regulated by ORAI1, are crucial for male fertility. Orai1(-/-) mice show sterility and impaired spermatogenesis, highlighting ORAI1

Area of Science:

  • Cell Biology
  • Reproductive Biology
  • Immunology

Background:

  • Store-operated calcium entry (SOCE) is a vital Ca(2+) influx pathway in somatic cells, regulating endoplasmic reticulum (ER) Ca(2+) stores and signaling pathways.
  • Mutations in ORAI1, a key component of SOCE channels, cause severe immunodeficiency, myopathy, and ectodermal dysplasia in humans.
  • The role of ORAI1 in germ cells and male reproductive function remains largely unexplored due to limited survival of affected males.

Purpose of the Study:

  • To investigate the essential role of ORAI1 in male reproductive function and fertility in vivo.
  • To elucidate the impact of ORAI1 deficiency on spermatogenesis and male fertility.

Main Methods:

  • Utilized Orai1 knockout (Orai1(-/-)) male mice to assess reproductive function.
  • Examined spermatogenesis, focusing on sperm development stages, in Orai1(-/-) mice.
  • Evaluated the in vivo function of store-operated ORAI1 channels in male fertility.

Main Results:

  • Orai1(-/-) male mice were found to be sterile, exhibiting severe defects in spermatogenesis.
  • A prominent deficiency was observed in mid- to late-stage elongating spermatid development in knockout mice.
  • These findings demonstrate a critical requirement for ORAI1 in male germ cell development and sperm production.

Conclusions:

  • Store-operated ORAI1 channels play an essential in vivo role in maintaining male reproductive function.
  • ORAI1 is identified as a potential non-steroidal regulator of male fertility.
  • Further research into ORAI1 function could reveal novel therapeutic targets for male infertility.
Keywords:
Ca(2+)FertilityOrai1ReproductionSpermatogenesisStore-operated calcium entry (SOCE)

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