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

Tokuhiro, K.; Satouh, Y.; Nozawa, K.; Isotani, A.; Fujihara, Y.; Hirashima, Y.; Matsumura, H.; Takumi, K.; Miyano, T.; Okabe, M.; Benham, A.M.; Ikawa, M.

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Authors

K. Tokuhiro

Y. Satouh

K. Nozawa

A. Isotani

Y. Fujihara

Y. Hirashima

H. Matsumura

K. Takumi

T. Miyano

M. Okabe

M. Ikawa



Abstract

Calnexin (CANX) and calreticulin (CALR) chaperones mediate nascent glycoprotein folding in the endoplasmic reticulum. Here we report that these chaperones have distinct roles in male and female fertility. Canx null mice are growth retarded but fertile. Calr null mice die during embryonic development, rendering indeterminate any effect on reproduction. Therefore, we conditionally ablated Calr in male and female germ cells using Stra8 (mcKO) and Zp3 (fcKO) promoter-driven Cre recombinase, respectively. Calr mcKO male mice were fertile, but fcKO female mice were sterile despite normal mating behavior. Strikingly, we found that Calr fcKO female mice had impaired folliculogenesis and decreased ovulatory rates due to defective proliferation of cuboidal granulosa cells. Oocyte-derived, TGF-beta family proteins play a major role in follicular development and molecular analysis revealed that the normal processing of GDF9 and BMP15 was defective in Calr fcKO oocytes. These findings highlight the importance of CALR in female reproduction and demonstrate that compromised CALR function leads to ovarian insufficiency and female infertility.

Citation

Tokuhiro, K., Satouh, Y., Nozawa, K., Isotani, A., Fujihara, Y., Hirashima, Y., …Ikawa, M. (2015). Calreticulin is required for development of the cumulus oocyte complex and female fertility. Scientific Reports, 5, https://doi.org/10.1038/srep14254

Journal Article Type Article
Acceptance Date Aug 21, 2015
Online Publication Date Sep 21, 2015
Publication Date Sep 21, 2015
Deposit Date Nov 30, 2015
Publicly Available Date Dec 2, 2015
Journal Scientific Reports
Publisher Nature Research
Peer Reviewed Peer Reviewed
Volume 5
DOI https://doi.org/10.1038/srep14254

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http://creativecommons.org/licenses/by/4.0/

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This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/







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