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Here we report that these chaperones have distinct roles in male and female fertility. <jats:italic>Canx<\/jats:italic> null mice are growth retarded but fertile. <jats:italic>Calr<\/jats:italic> null mice die during embryonic development, rendering indeterminate any effect on reproduction. Therefore, we conditionally ablated <jats:italic>Calr<\/jats:italic> in male and female germ cells using <jats:italic>Stra8<\/jats:italic> (mcKO) and <jats:italic>Zp3<\/jats:italic> (fcKO) promoter-driven Cre recombinase, respectively. <jats:italic>Calr<\/jats:italic> mcKO male mice were fertile, but fcKO female mice were sterile despite normal mating behavior. Strikingly, we found that <jats:italic>Calr<\/jats:italic> 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 <jats:italic>Calr<\/jats:italic> 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.<\/jats:p>","DOI":"10.1038\/srep14254","type":"journal-article","created":{"date-parts":[[2015,9,21]],"date-time":"2015-09-21T09:37:30Z","timestamp":1442828250000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Calreticulin is required for development of the cumulus oocyte complex and female fertility"],"prefix":"10.1038","volume":"5","author":[{"given":"Keizo","family":"Tokuhiro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhkoh","family":"Satouh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Nozawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Isotani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Fujihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumiko","family":"Hirashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Matsumura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Takumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Miyano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Okabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam M.","family":"Benham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahito","family":"Ikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,9,21]]},"reference":[{"key":"BFsrep14254_CR1","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1146\/annurev-biochem-062209-093836","volume":"80","author":"I Braakman","year":"2011","unstructured":"Braakman, I. & Bulleid, N. 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