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Calreticulin is required for development of the cumulus oocyte complex and female fertility

Keizo Tokuhiro1, Yuhkoh Satouh1, Kaori Nozawa1,2

  • 1Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.

Scientific Reports
|September 22, 2015
PubMed

Insights

Calreticulin (CALR) is crucial for female fertility. Ablating CALR in female mice caused infertility due to impaired ovarian development and defective oocyte function, highlighting its reproductive importance.

Area of Science:

  • Endocrinology
  • Reproductive Biology
  • Molecular Biology

Background:

  • Calnexin (CANX) and calreticulin (CALR) are endoplasmic reticulum chaperones essential for glycoprotein folding.
  • Distinct roles for CANX and CALR in male and female fertility are suggested by preliminary studies.
  • Calr null mice exhibit embryonic lethality, precluding direct assessment of reproductive roles.

Purpose of the Study:

  • To investigate the specific roles of calreticulin (CALR) in male and female fertility.
  • To determine the impact of CALR deficiency on reproductive organs and gametogenesis.
  • To elucidate the molecular mechanisms underlying CALR's function in reproduction.

Main Methods:

  • Conditional ablation of Calr in male germ cells (mcKO) and female germ cells (fcKO) using Stra8 and Zp3 promoter-driven Cre recombinase, respectively.
  • Assessment of fertility in Calr mcKO and fcKO mice.
  • Histological analysis of ovarian follicles and granulosa cells.
  • Molecular analysis of TGF-beta family proteins (GDF9 and BMP15) in oocytes.

Main Results:

  • Calr mcKO male mice were fertile.
  • Calr fcKO female mice were sterile despite normal mating behavior.
  • Calr fcKO females exhibited impaired folliculogenesis and reduced ovulatory rates due to defective granulosa cell proliferation.
  • Processing of oocyte-derived GDF9 and BMP15 was defective in Calr fcKO oocytes.

Conclusions:

  • Calreticulin (CALR) plays a critical role in female reproduction.
  • Compromised CALR function leads to ovarian insufficiency and female infertility.
  • CALR is essential for proper folliculogenesis and oocyte-derived growth factor processing.

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