{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:57:37Z","timestamp":1785405457712,"version":"3.56.0"},"posted":{"date-parts":[[2026,3,28]]},"group-title":"Physiology","reference-count":10,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R01ES032144"],"award-info":[{"award-number":["R01ES032144"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30ES005022"],"award-info":[{"award-number":["P30ES005022"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01HD114750"],"award-info":[{"award-number":["R01HD114750"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["PC129-22"],"award-info":[{"award-number":["PC129-22"]}],"id":[{"id":"https:\/\/ror.org\/040may582","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The human endometrium undergoes cyclic, hormone-driven remodeling that establishes a transient window of receptivity required for embryo implantation, placentation, and maintenance of pregnancy. Decidualization of endometrial stromal cells is a central component of this process and can be induced\n                  <jats:italic>in vitro<\/jats:italic>\n                  using cAMP alone or in combination with ovarian steroid hormones (EPC: estradiol, progesterone, and cAMP). Although cAMP activates the core decidual transcriptional program, whether hormone supplementation induces a more physiologically relevant response remains unclear, particularly in 3D endometrial organoid (Endo-organoid) models which have emerged as a new alternative methodology (NAM). Here, we compared morphological and transcriptomic responses of human endometrial stromal cell-derived Endo-organoids undergoing decidualization induced by cAMP or EPC stimulation. EPC-treated Endo-organoids exhibited enhanced structural remodeling and more advanced morphological transformation compared with cAMP-treated organoids. RNA-seq analysis revealed substantial overlap in canonical decidual gene expression between the two conditions, but EPC induced broader transcriptional and pathway-level changes, including enrichment of metabolic, stress-response, and differentiation-related processes. Together, these findings demonstrate that while cAMP activates the core decidual program, EPC elicits a broader and more physiologically relevant decidualization response in 3D human Endo-organoids, providing guidance for optimizing Endo-organoids to study endometrial receptivity, implantation, and early pregnancy success.\n                <\/jats:p>","DOI":"10.64898\/2026.03.25.714293","type":"posted-content","created":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T04:35:15Z","timestamp":1774758915000},"source":"Crossref","is-referenced-by-count":0,"title":["Hormonal stimulation induces broader decidualization responses than cAMP alone in 3D human endometrial organoids"],"prefix":"10.64898","author":[{"given":"Shichao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA"},{"name":"Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA"},{"name":"Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingjie","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA"},{"name":"Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8678-7013","authenticated-orcid":false,"given":"Qiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataki C.","family":"Douglas","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Health, New Jersey Medical School (NJMS), Rutgers University, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqin","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA"},{"name":"Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026040103501060000_2026.03.25.714293v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14584"},{"key":"2026040103501060000_2026.03.25.714293v1.2","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.medj.2023.07.004","article-title":"Organoid co-culture model of the human endometrium in a fully synthetic extracellular matrix enables the study of epithelial-stromal crosstalk","volume":"4","year":"2023","journal-title":"Med"},{"key":"2026040103501060000_2026.03.25.714293v1.3","doi-asserted-by":"crossref","first-page":"10439","DOI":"10.1038\/s41467-025-65406-7","article-title":"Microengineered patient-derived endometrium-on-a-chip for the evaluation of endometrial receptivity and personalised translational medicine","volume":"16","year":"2025","journal-title":"Nat Commun"},{"key":"2026040103501060000_2026.03.25.714293v1.4","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.cell.2025.10.026","article-title":"A 3D in vitro model for studying human implantation and implantation failure","volume":"189","year":"2026","journal-title":"Cell"},{"key":"2026040103501060000_2026.03.25.714293v1.5","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.stem.2025.12.002","article-title":"3D post-implantation co-culture of human embryo and endometrium","volume":"33","year":"2026","journal-title":"Cell Stem 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endometrium","volume":"27","year":"2024","journal-title":"iScience"},{"key":"2026040103501060000_2026.03.25.714293v1.8","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq636"},{"key":"2026040103501060000_2026.03.25.714293v1.9","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7"},{"key":"2026040103501060000_2026.03.25.714293v1.10","doi-asserted-by":"publisher","DOI":"10.1002\/rmb2.12088"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.03.25.714293","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T10:50:20Z","timestamp":1775040620000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.03.25.714293"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,28]]},"references-count":10,"URL":"https:\/\/doi.org\/10.64898\/2026.03.25.714293","relation":{},"subject":[],"published":{"date-parts":[[2026,3,28]]},"subtype":"preprint"}}