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Although this process is integral to fertility, many of the intricate molecular mechanisms contributing to decidualization remain undefined. One pathway that has been implicated in endometrial stromal cell decidualization in humans\n                      <jats:italic>in vitro<\/jats:italic>\n                      is the HIPPO signaling pathway. Two previously conducted studies showed that the effectors of the HIPPO signaling pathway YAP1 and WWTR1 are required for decidualization of primary endometrial stromal cells\n                      <jats:italic>in vitro<\/jats:italic>\n                      . To investigate the\n                      <jats:italic>in vivo<\/jats:italic>\n                      role of YAP1 and WWTR1 in decidualization and pregnancy initiation, we generated progesterone receptor Cre-mediated mutation of a combination of\n                      <jats:italic>Yap1<\/jats:italic>\n                      and\n                      <jats:italic>Wwtr1<\/jats:italic>\n                      alleles. Female\n                      <jats:italic>Yap1<\/jats:italic>\n                      and\n                      <jats:italic>Wwtr1<\/jats:italic>\n                      triple allele mutants exhibited subfertility, a compromised decidualization response, decreased endometrial receptivity, delayed embryonic development and a unique transcriptional profile at 7.5 days post-coitus (dpc). Bulk mRNA sequencing revealed aberrant maternal remodeling evidenced by significant alterations in extracellular matrix-encoding genes at 7.5 dpc in mutant dams and enrichment for terms associated with fertility-compromising diseases such as pre-eclampsia and endometriosis. In addition, differentially expressed genes overlapped directionally with estrogen receptor- and epidermal growth factor receptor-regulated genes as identified by microarray. Our results indicate that\n                      <jats:italic>Yap1<\/jats:italic>\n                      and\n                      <jats:italic>Wwtr1<\/jats:italic>\n                      are necessary for successful mammalian pregnancy initiation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/rep-24-0355","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T09:22:54Z","timestamp":1730884974000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-11","source":"Crossref","is-referenced-by-count":0,"title":["YAP1 and WWTR1 are required for murine pregnancy initiation"],"prefix":"10.1093","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8297-2441","authenticated-orcid":true,"given":"Genna E","family":"Moldovan","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Gynecology & Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, Michigan, USA"},{"name":"Cell and Molecular Biology Program, College of Natural Sciences, Michigan State University, East Lansing, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noura","family":"Massri","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology & Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, Michigan, USA"},{"name":"Cell and Molecular Biology Program, College of Natural Sciences, Michigan State University, East Lansing, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin L","family":"Vegter","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology & Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivonne N","family":"Pauneto-Delgado","sequence":"additional","affiliation":[{"name":"University of Puerto Rico Humacao, Humacao, Puerto Rico, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0021-4319","authenticated-orcid":true,"given":"Gregory W","family":"Burns","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology & Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niraj","family":"Joshi","sequence":"additional","affiliation":[{"name":"AbbVie, North Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5594-2463","authenticated-orcid":true,"given":"Bin","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology & Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, Michigan, USA"},{"name":"Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5051-6724","authenticated-orcid":true,"given":"Ripla","family":"Arora","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology & Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, Michigan, USA"},{"name":"Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asgerally T","family":"Fazleabas","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology & Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","reference":[{"key":"bib1","series-title":"Commun Biol","first-page":"1237","article-title":"EGFR regulates the Hippo pathway by promoting the tyrosine phosphorylation of MOB1","volume":"4","author":"Ando T","year":"2021","unstructured":"Ando T, Arang N, Wang Z, et al. 2021 EGFR regulates the Hippo pathway by promoting the tyrosine phosphorylation of MOB1. 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