{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T09:47:05Z","timestamp":1778924825705,"version":"3.51.4"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,1,3]],"date-time":"2018-01-03T00:00:00Z","timestamp":1514937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:p>\n                    The harmonized actions of ovarian E\n                    <jats:sub>2<\/jats:sub>\n                    and progesterone (P\n                    <jats:sub>4<\/jats:sub>\n                    ) regulate the proliferation and differentiation of uterine cells in a spatiotemporal manner. Imbalances between these hormones often lead to infertility and gynecologic diseases. Whereas numerous factors that are involved in P\n                    <jats:sub>4<\/jats:sub>\n                    signaling have been identified, few local factors that mediate E2 actions in the uterus have been revealed. Here, we demonstrate that estrogen induces the transcription factor, early growth response 1 (\n                    <jats:italic>Egr1<\/jats:italic>\n                    ), to fine\u2010tune its actions in uterine epithelial cells (ECs) that are responsible for uterine receptivity for embryo implantation. In the presence of exogenous gonadotrophins, ovulation, fertilization, and embryonic development normally occur in\n                    <jats:italic>\n                      Egr1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice, but these animals experience the complete failure of embryo implantation with reduced artificial decidualization. Although serum levels of E\n                    <jats:sub>2<\/jats:sub>\n                    and P\n                    <jats:sub>4<\/jats:sub>\n                    were comparable between\n                    <jats:italic>\n                      Egr1\n                      <jats:sup>+\/+<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic>\n                      Egr1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice on d 4 of pregnancy, aberrantly reduced levels of progesterone receptor in\n                    <jats:italic>\n                      Egr1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    uterine ECs caused enhanced E\n                    <jats:sub>2<\/jats:sub>\n                    activity and impaired P\n                    <jats:sub>4<\/jats:sub>\n                    response. Ultra\u2010 structural analyses revealed that\n                    <jats:italic>\n                      Egr1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    ECs are not fully able to provide proper uterine receptivity. Uterine mRNA landscapes in\n                    <jats:italic>\n                      Egr1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice revealed that EGR1 controls the expression of a subset of E\n                    <jats:sub>2<\/jats:sub>\n                    \u2010regulated genes. In addition, P\n                    <jats:sub>4<\/jats:sub>\n                    signaling was unable to modulate estrogen actions, including those that are involved in cell\u2010cycle progression, in ECs that were deficient in EGR1. Furthermore, primary coculture of\n                    <jats:italic>\n                      Egr1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    ECs with\n                    <jats:italic>\n                      Egr1\n                      <jats:sup>+\/+<\/jats:sup>\n                    <\/jats:italic>\n                    stromal cells, and\n                    <jats:italic>vice versa<\/jats:italic>\n                    , supported the notion that\n                    <jats:italic>Egr1<\/jats:italic>\n                    is required to modulate E\n                    <jats:sub>2<\/jats:sub>\n                    actions on ECs to prepare the uterine environment for embryo implantation. In contrast to its role in ECs, loss of\n                    <jats:italic>Egr1<\/jats:italic>\n                    in stroma significantly reduced stromal cell proliferation. Collectively, our results demonstrate that E\n                    <jats:sub>2<\/jats:sub>\n                    induces EGR1 to streamline its actions for the preparation of uterine receptivity for embryo implantation in mice.\u2014Kim, H.\u2010R., Kim, Y. S., Yoon, J. A., Yang, S. C., Park, M., Seol, D.\u2010W., Lyu, S. W., Jun, J. H., Lim, H. J., Lee, D. R., Song, H. Estrogen induces EGR1 to fine\u2010tune its actions on uterine epithelium by controlling PR signaling for successful embryo implantation. FASEB J. 32,1184\u20101195 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201700854rr","type":"journal-article","created":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T11:20:12Z","timestamp":1509535212000},"page":"1184-1195","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Estrogen induces EGR1 to fine\u2010tune its actions on uterine epithelium by controlling PR signaling for successful embryo implantation"],"prefix":"10.1096","volume":"32","author":[{"given":"Hye\u2010Ryun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biomedical Science CHA University Seongnam Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeon Sun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science CHA University Seongnam Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung Ah","family":"Yoon","sequence":"additional","affiliation":[{"name":"Fertility Center of CHA Gangnam Medical Center, CHA University Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung Chel","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science CHA University Seongnam Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mira","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science CHA University Seongnam Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong\u2010Won","family":"Seol","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science CHA University Seongnam Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Woo","family":"Lyu","sequence":"additional","affiliation":[{"name":"Fertility Center of CHA Gangnam Medical Center, CHA University Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Hyun","family":"Jun","sequence":"additional","affiliation":[{"name":"Department of Biomedical Laboratory Science Graduate School of Health Science, Eulji University Seongnam Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyunjung Jade","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine Konkuk University Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong Ryul","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science CHA University Seongnam Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haengseok","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science CHA University Seongnam Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,1,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.4.2275"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4131"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.21.15030"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms131013104"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/337461a0"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90329-O"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.7.11.2071"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/371796a0"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200501156"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.22.5061"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5279.1219"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend.12.1.0049"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2014.12.013"},{"key":"e_1_2_8_15_1","unstructured":"Andrade J. 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