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

Tokuhiro, Keizo; Satouh, Yuhkoh; Nozawa, Kaori; Isotani, Ayako; Fujihara, Yoshitaka; Hirashima, Yumiko; Matsumura, Hiroyuki; Takumi, Kazuhiro; Miyano, Takashi; Okabe, Masaru; Benham, Adam M.; Ikawa, Masahito

doi:https://doi.org/10.1038/srep14254

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

Tokuhiro, Keizo; Satouh, Yuhkoh; Nozawa, Kaori et al.

Scientific Reports, 2015, 5, 14254

Number of Access:863（2025-08-22 01:06 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/78596

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Title	Calreticulin is required for development of the cumulus oocyte complex and female fertility
Creator	CreatorName Tokuhiro, Keizo
	NRID 1000040545571 1000040545571 CreatorName Satouh, Yuhkoh
	CreatorName Nozawa, Kaori
	NRID 1000020444523 1000020444523 CreatorName Isotani, Ayako
	NRID 1000070578848 1000070578848 CreatorName Fujihara, Yoshitaka
	CreatorName Hirashima, Yumiko
	CreatorName Matsumura, Hiroyuki
	CreatorName Takumi, Kazuhiro
	NRID 1000080200195 1000080200195 CreatorName Miyano, Takashi
	NRID 1000030089875 1000030089875 CreatorName Okabe, Masaru
	CreatorName Benham, Adam M.
	NRID 1000020304066 1000020304066 ORCID 0000-0001-9859-6217 0000-0001-9859-6217 researchmap permalink read0054910 read0054910 Scopus Author ID 16689054500 16689054500 CreatorName Ikawa, Masahito
Description	Tokuhiro, K., Satouh, Y., Nozawa, K. et al. Calreticulin is required for development of the cumulus oocyte complex and female fertility. Sci Rep 5, 14254 (2015). https://doi.org/10.1038/srep14254
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.
Publisher	Nature Research
Source Title	Scientific Reports
Volume (Issue)	5
Page	14254
Date of Issued	2015-09-21
Language	English
Handle URL	https://hdl.handle.net/11094/78596
eISSN	20452322
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/srep14254
Relation.isIdenticalTo	PMID 26388295
Access Rights	open access
CopyRight	© 2015 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Scientific Reports. 2015, 5, p. 14254
DC.title	Calreticulin is required for development of the cumulus oocyte complex and female fertility
DC.creator	Tokuhiro, Keizo
	Satouh, Yuhkoh
	Nozawa, Kaori
	Isotani, Ayako
	Fujihara, Yoshitaka
	Hirashima, Yumiko
	Matsumura, Hiroyuki
	Takumi, Kazuhiro
	Miyano, Takashi
	Okabe, Masaru
	Benham, Adam M.
	Ikawa, Masahito
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2015-09-21
DC.identifier	https://doi.org/10.1038/srep14254
DC.description	Tokuhiro, K., Satouh, Y., Nozawa, K. et al. Calreticulin is required for development of the cumulus oocyte complex and female fertility. Sci Rep 5, 14254 (2015). https://doi.org/10.1038/srep14254
DCTERMS.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.
DC.rights	© 2015 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	78596
citation_title	Calreticulin is required for development of the cumulus oocyte complex and female fertility
citation_author	Tokuhiro, Keizo
	Satouh, Yuhkoh
	Nozawa, Kaori
	Isotani, Ayako
	Fujihara, Yoshitaka
	Hirashima, Yumiko
	Matsumura, Hiroyuki
	Takumi, Kazuhiro
	Miyano, Takashi
	Okabe, Masaru
	Benham, Adam M.
	Ikawa, Masahito
citation_publisher	Nature Research
citation_language	English
citation_date	2015-09-21
citation_journal_title	Scientific Reports
citation_volume	5
citation_firstpage	14254
citation_doi	https://doi.org/10.1038/srep14254
citation_pmid	26388295
citation_public_url	https://hdl.handle.net/11094/78596

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

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