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In the follicles of mammalian ovaries, N-cadherin adherens junctions are present between granulosa cells, cumulus cells, and at the interface of cumulus cell transzonal projections and the oocyte. We demonstrate a mechanosensory role of N-cadherin integrating tissue structure and hormonal regulation of follicular morphogenic events including expansion of the cumulus\u2013oocyte complex (COC) matrix, oocyte maturation, and ovulation. Two small molecule N-cadherin antagonists inhibited COC maturation in vitro. Transcriptome profiling revealed that targets of \u03b2-catenin and YAP1 pathways were dysregulated by N-cadherin antagonists. In vivo, N-cadherin antagonist significantly reduced ovulation in mice compared to controls (11 vs 26 oocytes\/ovary; p = 5.8 \u00d7 10\n                    <jats:sup>\u22126<\/jats:sup>\n                    ). Ovarian follicles exhibited structural dysgenesis with granulosa and cumulus cell layers becoming disorganised and the connection between cumulus cells and the oocyte disrupted and the transcriptome again indicated altered mechanical sensing causing dysregulation of the Hippo\/YAP and \u03b2-catenin pathways and extracellular matrix reorganisation. Granulosa-specific N-cadherin depletion in\n                    <jats:italic>Cdh2<\/jats:italic>\n                    <jats:sup>Fl\/FL<\/jats:sup>\n                    ;\n                    <jats:italic>Amhr2<\/jats:italic>\n                    <jats:sup>Cre\/+<\/jats:sup>\n                    also showed significantly altered mechanosensitive gene expression and reduced ovulation. Our findings demonstrate a critical role for N-cadherin in ovarian follicular development and ovulation, and the potential to inhibit ovulation through targeting this signalling mechanism.\n                  <\/jats:p>","DOI":"10.7554\/elife.92068","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T12:25:08Z","timestamp":1705580708000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.92068","source":"Crossref","is-referenced-by-count":7,"title":["N-cadherin mechanosensing in ovarian follicles controls oocyte maturation and ovulation"],"prefix":"10.7554","volume":"13","author":[{"given":"Alaknanda","family":"Emery","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00892tw58","id-type":"ROR","asserted-by":"publisher"}],"name":"Robinson Research Institute, Adelaide Medical School, The University of Adelaide","place":["Adelaide, Australia"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9448-4979","authenticated-orcid":true,"given":"Orest W","family":"Blaschuk","sequence":"additional","affiliation":[{"name":"Zonula Incorporated","place":["Kirkland, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Doan T","family":"Dinh","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00892tw58","id-type":"ROR","asserted-by":"publisher"}],"name":"Robinson Research Institute, Adelaide Medical School, The University of Adelaide","place":["Adelaide, Australia"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Tim","family":"McPhee","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00892tw58","id-type":"ROR","asserted-by":"publisher"}],"name":"Robinson Research Institute, Adelaide Medical School, The University of Adelaide","place":["Adelaide, Australia"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Rouven","family":"Becker","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00892tw58","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, The University of Adelaide","place":["Adelaide, Australia"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Andrew D","family":"Abell","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00892tw58","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, The University of Adelaide","place":["Adelaide, Australia"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Krzysztof M","family":"Mrozik","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00892tw58","id-type":"ROR","asserted-by":"publisher"}],"name":"Myeloma Research Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, Australia. 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