{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:03:52Z","timestamp":1791198232180,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,29]]},"group-title":"Pharmacology and Toxicology","reference-count":31,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH","award":["R01ES032144"],"award-info":[{"award-number":["R01ES032144"]}]},{"name":"NIH","award":["OT2OD042764"],"award-info":[{"award-number":["OT2OD042764"]}]},{"name":"NIH","award":["R01ES035766"],"award-info":[{"award-number":["R01ES035766"]}]},{"name":"NIH","award":["P30ES005022"],"award-info":[{"award-number":["P30ES005022"]}]},{"name":"NIH","award":["R01HD114750"],"award-info":[{"award-number":["R01HD114750"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,29]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Female infertility remains a major women\u2019s reproductive health challenge, with impaired endometrial receptivity contributing to recurrent implantation failure, early pregnancy loss, and pregnancy complications. Mechanistic studies of human early pregnancy are limited by the lack of physiologically relevant models, and existing\n                  <jats:italic>in vitro<\/jats:italic>\n                  endometrial models rely on exogenous hormone treatment and do not recapitulate the dynamic ovarian control of endometrial growth and differentiation. Here, as a proof of concept, we developed a 3D\n                  <jats:italic>in vitro<\/jats:italic>\n                  ovarian follicle-endometrial organoid co-culture model. Immature murine follicles were cultured\n                  <jats:italic>in vitro<\/jats:italic>\n                  to obtain preovulatory follicles, followed by human chorionic gonadotropin (hCG) stimulation to induce ovulation and luteinization. Luteinized follicles were co-cultured with human endometrial stroma organoids for 6 days. The results showed that luteinized follicles generated a dynamic endocrine environment characterized by progressively increasing progesterone levels and declining estradiol levels. Follicle co-culture induced morphological differentiation and expression of decidualization markers in human endo-organoids. Transcriptomic analysis revealed strong genome-wide concordance between follicle co-culture and conventional decidualization induction using estradiol\/progesterone\/cAMP (EPC), with significant enrichment of decidualization-associated genes and pathways under both conditions. Nevertheless, the two conditions also exhibited distinct transcriptional states, with EPC preferentially enriched for more mature decidualization-associated programs, whereas luteinized follicle co-culture retained features of the early stage of decidualization. Functional perturbation testing revealed that the progesterone receptor (PR) antagonist RU486 attenuated co-culture-induced endometrial decidualization. Together, these results establish a new\n                  <jats:italic>in vitro<\/jats:italic>\n                  new approach methodology (NAM) that recapitulates ovarian control of endometrial decidualization. This platform provides a human-relevant NAM model to investigate the physiology and pathophysiology of endometrial decidualization, and to evaluate how drugs and environmental chemicals perturb uterine receptivity and early pregnancy.\n                <\/jats:p>","DOI":"10.64898\/2026.09.24.754184","type":"posted-content","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:05:17Z","timestamp":1790744717000},"source":"Crossref","is-referenced-by-count":0,"title":["A 3D\n                  <i>in vitro<\/i>\n                  follicle-endometrial organoid co-culture model recapitulates ovarian control of human endometrial decidualization"],"prefix":"10.64898","author":[{"given":"Yubing","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Environmental and Occupational Health Sciences Institute, 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, Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Environmental and Occupational Health Sciences Institute, 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, Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Fielding School of Public Health, University of California, Los Angeles, CA 90095, 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, Rutgers University, Newark, NJ 07103, 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":"Shuo","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026100503450780000_2026.09.24.754184v1.1","doi-asserted-by":"publisher","DOI":"10.1002\/rmb2.12088"},{"key":"2026100503450780000_2026.09.24.754184v1.2","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmab003"},{"key":"2026100503450780000_2026.09.24.754184v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)61028-2"},{"key":"2026100503450780000_2026.09.24.754184v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/0960-0760(92)90137-8"},{"key":"2026100503450780000_2026.09.24.754184v1.5","doi-asserted-by":"publisher","DOI":"10.1007\/BF02820507"},{"issue":"1","key":"2026100503450780000_2026.09.24.754184v1.6","first-page":"105","article-title":"Establishment and characterization of in vitro decidualization in normal human endometrial stromal cells","volume":"44","year":"1998","journal-title":"Osaka City Med J"},{"key":"2026100503450780000_2026.09.24.754184v1.7","doi-asserted-by":"crossref","first-page":"1220622","DOI":"10.3389\/fendo.2023.1220622","article-title":"From cup to dish: how to make and use endometrial organoid and stromal cultures derived from menstrual fluid","volume":"14","year":"2023","journal-title":"Front Endocrinol (Lausanne"},{"key":"2026100503450780000_2026.09.24.754184v1.8","doi-asserted-by":"crossref","unstructured":"Fitzgerald, H.C. , et al., Basolateral secretions of human endometrial epithelial organoids impact stromal cell decidualization. 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