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We sought to understand the role of ERK1\/2 signaling in cells expressing a Cre allele regulated by the endogenous\n                    <jats:italic>GnRHR<\/jats:italic>\n                    promoter (GRIC-ERKdko). Adult female GRIC-ERKdko mice were hypogonadotropic and anovulatory. Gonadotropin administration and mating led to pregnancy in one-third of the ERKdko females. Litters from ERKdko females and pup weights were reduced coincident with delayed parturition and 100% neonatal mortality. Based on this, we examined Cre expression in implantation sites as a potential mechanism.\n                    <jats:italic>GnRHR<\/jats:italic>\n                    mRNA levels at e10.5 and e12.5 were comparable to pituitary levels from adult female mice at proestrus and\n                    <jats:italic>GnRHR<\/jats:italic>\n                    mRNA in decidua was enriched compared to whole implantation site.\n                    <jats:italic>In vivo<\/jats:italic>\n                    studies confirmed recombination in decidua, and GRIC-ERKdko placentas showed reduced ERK2 expression. Histopathology revealed abnormalities in placental architecture in the GRIC-ERKdko animals. Regions of apoptosis at the decidual\/uterine interface at e18.5 were observed in control animals but apoptotic tone in these regions was reduced in ERKdko animals. These studies support a potential model of ERK-dependent signaling within the implantation site leading to loss of placental architecture and mis-regulation of apoptotic events at parturition occurring coincident with prolonged gestation and neonatal mortality.\n                  <\/jats:p>","DOI":"10.1038\/s41598-019-45997-0","type":"journal-article","created":{"date-parts":[[2019,7,3]],"date-time":"2019-07-03T06:03:04Z","timestamp":1562133784000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse"],"prefix":"10.1038","volume":"9","author":[{"given":"Jessica L.","family":"Brown","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Sones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia N.","family":"Angulo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keelin","family":"Abbott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6350-5581","authenticated-orcid":false,"given":"Andrew D.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Boehm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Roberson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,7,3]]},"reference":[{"key":"45997_CR1","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1096\/fj.06-7859rev","volume":"22","author":"MR Junttila","year":"2008","unstructured":"Junttila, M. 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