{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T23:13:25Z","timestamp":1767568405083,"version":"3.48.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"2","funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["MOP-142445"],"award-info":[{"award-number":["MOP-142445"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["R24HD102061"],"award-info":[{"award-number":["R24HD102061"]}]}],"content-domain":{"domain":["rep.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7,11]]},"abstract":"<jats:sec>\n                    <jats:title>In brief<\/jats:title>\n                    <jats:p>The Hippo signaling pathway plays crucial roles in various processes related to development and tissue homeostasis. This study demonstrates that sustained YAP1 activity can influence cell fate within the reproductive system, specifically in lutein and M\u00fcllerian mesenchymal cells, causing them to transdifferentiate into myofibroblasts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Recent reports have suggested that the Hippo intracellular signaling pathway is required for homeostasis in a variety of tissues, including the ovary and female reproductive tract. To further define the role of the Hippo effector YAP1 in the female reproductive system, transgenic mouse models were designed to direct the expression of a dominant stable mutant form of YAP1, termed YAP5SA, to the granulosa cells of antral follicles (\n                      <jats:italic>\n                        R26\n                        <jats:sup>YAP5SA<\/jats:sup>\n                      <\/jats:italic>\n                      ;\n                      <jats:italic>CYP19<\/jats:italic>\n                      -cre) and M\u00fcllerian mesenchymal cells (\n                      <jats:italic>\n                        R26\n                        <jats:sup>YAP5SA<\/jats:sup>\n                      <\/jats:italic>\n                      ;\n                      <jats:italic>Amhr2<\/jats:italic>\n                      <jats:sup>cre\/+<\/jats:sup>\n                      ). Unexpectedly, YAP5SA expression in the ovaries of\n                      <jats:italic>\n                        R26\n                        <jats:sup>YAP5SA<\/jats:sup>\n                      <\/jats:italic>\n                      ;\n                      <jats:italic>CYP19<\/jats:italic>\n                      -cre mice was not detected in granulosa cells, but rather in a subset of lutein cells. This caused the lutein cells to transdifferentiate into cells having the morphologic and functional properties of myofibroblasts, including collagen deposition. These cells coalesced into roughly spherical lesions that persisted in the ovaries, but did not interfere with ovarian function or fertility. Seminiferous tubule-like structures also formed in the ovaries of adult\n                      <jats:italic>\n                        R26\n                        <jats:sup>YAP5SA<\/jats:sup>\n                      <\/jats:italic>\n                      ;\n                      <jats:italic>CYP19<\/jats:italic>\n                      -cre mice, containing SOX9-positive Sertoli-like cells but no germ cells. Although multi-lineage transdifferentiation had been reported in mice lacking the Hippo kinases\n                      <jats:italic>Lats1<\/jats:italic>\n                      and -\n                      <jats:italic>2<\/jats:italic>\n                      in their granulosa cells, comparative transcriptomic analyses of granulosa cells expressing YAP5SA\n                      <jats:italic>vs<\/jats:italic>\n                      granulosa cells lacking\n                      <jats:italic>Lats1\/2<\/jats:italic>\n                      showed few similarities in transcriptome alterations.\n                      <jats:italic>\n                        R26\n                        <jats:sup>YAP5SA<\/jats:sup>\n                      <\/jats:italic>\n                      ;\n                      <jats:italic>Amhr2<\/jats:italic>\n                      <jats:sup>cre\/+<\/jats:sup>\n                      mice had severe developmental defects of their reproductive tracts, which were attributed to the transdifferentiation of M\u00fcllerian mesenchymal cells into myofibroblasts during embryogenesis. Together, these results indicate that sustained YAP1 signaling induces transdifferentiation in lutein and M\u00fcllerian mesenchymal cells, and further underscores the role of Hippo signaling in the maintenance of their fates.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/rep-24-0450","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T18:08:56Z","timestamp":1752516536000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-11","source":"Crossref","is-referenced-by-count":0,"title":["Sustained YAP1 signaling alters the fates of lutein and M\u00fcllerian mesenchymal cells in mice"],"prefix":"10.1093","volume":"170","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2599-1242","authenticated-orcid":true,"given":"Michael","family":"B\u00e9rub\u00e9","sequence":"first","affiliation":[{"name":"Centre de Recherche en Reproduction et Fertilit\u00e9, Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, Saint-Hyacinthe, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6740-4160","authenticated-orcid":true,"given":"Samuel","family":"Gusscott","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Reproduction et Fertilit\u00e9, Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, Saint-Hyacinthe, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhao","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo","family":"Zamberlam","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Reproduction et Fertilit\u00e9, Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, Saint-Hyacinthe, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Boyer","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Reproduction et Fertilit\u00e9, Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, Saint-Hyacinthe, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillaume","family":"St-Jean","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Reproduction et Fertilit\u00e9, Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, Saint-Hyacinthe, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Brind\u2019Amour","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Reproduction et Fertilit\u00e9, Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, Saint-Hyacinthe, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4454-0589","authenticated-orcid":true,"given":"Derek","family":"Boerboom","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Reproduction et Fertilit\u00e9, Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, Saint-Hyacinthe, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","reference":[{"key":"bib1","series-title":"Int J Mol Sci","first-page":"14160","article-title":"FSH regulates YAP-TEAD transcriptional activity in bovine granulosa cells to allow the future dominant follicle to exert its augmented estrogenic capacity","volume":"23","author":"de Andrade LG","year":"2022","unstructured":"de Andrade LG\n, \nPortela VM\n, \nDos Santos EC\n, et al.\n 2022 FSH regulates YAP-TEAD transcriptional activity in bovine granulosa cells to allow the future dominant follicle to exert its augmented estrogenic capacity. 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