{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T10:14:23Z","timestamp":1768731263931,"version":"3.49.0"},"reference-count":61,"publisher":"The Endocrine Society","issue":"9","license":[{"start":{"date-parts":[[2020,6,28]],"date-time":"2020-06-28T00:00:00Z","timestamp":1593302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01 HD55379"],"award-info":[{"award-number":["R01 HD55379"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["U01 HD66439"],"award-info":[{"award-number":["U01 HD66439"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Implantation is a reproductive bottleneck in women, regulated by fluctuations in ovarian steroid hormone concentrations. However, other nuclear receptor ligands are modifiers of endometrial differentiation leading to successful pregnancy. In the present study we analyzed the effects of peroxisome-proliferator-activated receptor \u03b2\/\u03b4 (PPAR\u03b2\/\u03b4) activation on established cellular biomarkers of human endometrial differentiation (decidualization).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>The objective of this work is to test the effects of PPAR\u03b2\/\u03b4 ligation on human endometrial cell differentiation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Isolated primary human endometrial stromal cells (ESCs) were treated with synthetic (GW0742) or natural (all trans-retinoic acid, RA) ligands of PPAR\u03b2\/\u03b4, and also with receptor antagonists (GSK0660, PT-S58, and ST247) in the absence or presence of decidualizing hormones (10 nM estradiol, 100 nM progesterone, and 0.5 mM dibutyryl cAMP [3\u2032,5\u2032-cyclic adenosine 5\u2032-monophosphate]). In some cases interleukin (IL)-1\u03b2 was used as an inflammatory stimulus. Time course and dose-response relationships were evaluated to determine effects on panels of well characterized in vitro biomarkers of decidualization.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>PPAR\u03b2\/\u03b4, along with estrogen receptor \u03b1 (ER\u03b1) and PR-A and PR-B, were expressed in human endometrial tissue and isolated ESCs. GW0742 treatment enhanced hormone-mediated ESC decidualization in vitro as manifested by upregulation of prolactin, insulin-like growth factor-binding protein 1, IL-11, and vascular endothelial growth factor (VEGF) secretion and also increased expression of ER\u03b1, PR-A and PR-B, and connexin 43 (Cx43). RA treatment also increased VEGF, ER\u03b1, PR-A, and PR-B and an active, nonphosphorylated isoform of Cx43. IL-1\u03b2 and PPAR\u03b2\/\u03b4 antagonists inhibited biomarkers of endometrial differentiation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Ligands that activate PPAR\u03b2\/\u03b4 augment the in vitro expression of biomarkers of ESC decidualization. By contrast, PPAR\u03b2\/\u03b4 antagonists impaired decidualization markers. Drugs activating these receptors may have therapeutic benefits for embryonic implantation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa413","type":"journal-article","created":{"date-parts":[[2020,6,28]],"date-time":"2020-06-28T18:23:51Z","timestamp":1593368631000},"page":"2983-2995","source":"Crossref","is-referenced-by-count":9,"title":["Human Endometrial Stromal Cell Differentiation is Stimulated by PPAR\u03b2\/\u03b4 Activation: New Targets for Infertility?"],"prefix":"10.1210","volume":"105","author":[{"given":"Jie","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah L","family":"Berga","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah, 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