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Calreticulin is required for development of the cumulus oocyte complex and female fertility
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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4585710/ https://www.ncbi.nlm.nih.gov/pubmed/26388295 http://dx.doi.org/10.1038/srep14254 |
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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 |
author_facet | 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 |
author_sort | Tokuhiro, Keizo |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4585710 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45857102015-09-29 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 Sci Rep Article 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. Nature Publishing Group 2015-09-21 /pmc/articles/PMC4585710/ /pubmed/26388295 http://dx.doi.org/10.1038/srep14254 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ 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/ |
spellingShingle | Article 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 Calreticulin is required for development of the cumulus oocyte complex and female fertility |
title | Calreticulin is required for development of the cumulus oocyte complex and female fertility |
title_full | Calreticulin is required for development of the cumulus oocyte complex and female fertility |
title_fullStr | Calreticulin is required for development of the cumulus oocyte complex and female fertility |
title_full_unstemmed | Calreticulin is required for development of the cumulus oocyte complex and female fertility |
title_short | Calreticulin is required for development of the cumulus oocyte complex and female fertility |
title_sort | calreticulin is required for development of the cumulus oocyte complex and female fertility |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4585710/ https://www.ncbi.nlm.nih.gov/pubmed/26388295 http://dx.doi.org/10.1038/srep14254 |
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