{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T16:50:18Z","timestamp":1782233418019,"version":"3.54.5"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["R01-HD084380"],"award-info":[{"award-number":["R01-HD084380"]}]},{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Centers for Translational Research in Reproduction and Infertility","award":["P50-HD055764"],"award-info":[{"award-number":["P50-HD055764"]}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"crossref","award":["P30AR070155-05"],"award-info":[{"award-number":["P30AR070155-05"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100029613","name":"American Association of Obstetricians and Gynecologists Foundation","doi-asserted-by":"crossref","award":["ABOG\/AAOGF Award"],"award-info":[{"award-number":["ABOG\/AAOGF Award"]}],"id":[{"id":"10.13039\/100029613","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    <jats:bold>BACKGROUND.<\/jats:bold>\n                    In vitro fertilization (IVF) culminates in embryo transfer into a hormonally primed endometrium, often via a programmed cycle (PC) regimen postulated to influence hypertensive disorders of pregnancy (HDP) risk. We thus generated a single-cell atlas of PC endometrium to define cell type-specific differences relative to natural cycle (NC) endometrium, and evaluated whether PC-associated modulation of the window of implantation (WOI) endometrium influences angiogenic balance in pregnancy.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>METHODS.<\/jats:bold>\n                    Single-nucleus RNA-seq of prospectively collected PC and NC WOI endometrium. An independent prospective cohort of 548 singleton pregnancies was separately analyzed for maternal serum angiogenic markers (soluble fms-like tyrosine kinase-1; placental growth factor) and HDP incidence in PC- versus NC-conceived pregnancies, adjusting for clinical confounders and IVF use.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>RESULTS.<\/jats:bold>\n                    Prominent transcriptomic differences were observed between PC (\n                    <jats:italic>n<\/jats:italic>\n                    = 7; 48,843 nuclei) and NC (\n                    <jats:italic>n<\/jats:italic>\n                    = 9; 44,230 nuclei) WOI endometrium, particularly in glandular epithelium (682 up- and 979 down-regulated genes; adjusted\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05) and stromal fibroblasts (108 up- and 168 down-regulated). PC endometrium showed reduced uterine natural killer cell abundance, potentially from\n                    <jats:italic>CXCL14<\/jats:italic>\n                    downregulation. Functional enrichment revealed downregulation of embryo implantation, angiogenesis, and extracellular matrix remodeling pathways in PC. Altered cell-cell signaling in decidualization, angiogenesis, and inflammatory response was also observed. Despite these WOI perturbations, PC-conceived pregnancies were not associated with early gestational angiogenic imbalance or increased HDP risk.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>CONCLUSION.<\/jats:bold>\n                    PC endometrial preparation induced distinct cellular and signaling alterations in the WOI, but was not associated with subsequent development of angiogenic imbalance or HDP, thereby underscoring the resilience and adaptability of the early maternal-fetal interface.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>TRIAL REGISTRATION.<\/jats:bold>\n                    ClinicalTrials.gov NCT03799107.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>FUNDING.<\/jats:bold>\n                    ABOG\/AAOGF; NICHD-R01-HD084380; NCTRI-P50-HD055764; NIAMS-P30-AR070155.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.202443","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T16:07:09Z","timestamp":1782230829000},"source":"Crossref","is-referenced-by-count":0,"title":["Programmed cycle-induced endometrial perturbations do not independently influence angiogenic imbalance or hypertensive disorders in pregnancy"],"prefix":"10.1172","author":[{"given":"David","family":"Huang","sequence":"first","affiliation":[{"name":"Division of Reproductive Endocrinology & Infertility, Department of Obstetr, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Flynn","sequence":"additional","affiliation":[{"name":"CoLabs, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany R.","family":"Davidson","sequence":"additional","affiliation":[{"name":"CoLabs, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Irwin","sequence":"additional","affiliation":[{"name":"Center for Reproductive Sciences, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Naser","sequence":"additional","affiliation":[{"name":"CoLabs, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Laura","family":"Almonte","sequence":"additional","affiliation":[{"name":"Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology & Reproductive Sciences, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology & Reproductive Sciences, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fleurdeliza B.","family":"Rabara","sequence":"additional","affiliation":[{"name":"Division of Reproductive Endocrinology & Infertility, Department of Obstetr, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Wong","sequence":"additional","affiliation":[{"name":"Division of Reproductive Endocrinology & Infertility, Department of Obstetr, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia B.","family":"Zablotska","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell P.","family":"Rosen","sequence":"additional","affiliation":[{"name":"Division of Reproductive Endocrinology & Infertility, Department of Obstetr, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Wittmann","sequence":"additional","affiliation":[{"name":"CoLabs, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9703-2591","authenticated-orcid":true,"given":"Gabriela K.","family":"Fragiadakis","sequence":"additional","affiliation":[{"name":"CoLabs, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9110-6542","authenticated-orcid":true,"given":"Alexis J.","family":"Combes","sequence":"additional","affiliation":[{"name":"CoLabs, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7246-6083","authenticated-orcid":true,"given":"Marina","family":"Sirota","sequence":"additional","affiliation":[{"name":"Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelle I.","family":"Cedars","sequence":"additional","affiliation":[{"name":"Division of Reproductive Endocrinology & Infertility, Department of Obstetr, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda C.","family":"Giudice","sequence":"additional","affiliation":[{"name":"Division of Reproductive Endocrinology & Infertility, Department of Obstetr, UCSF, San Francisco, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,6,23]]},"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/insight.jci.org\/articles\/view\/202443\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T16:07:11Z","timestamp":1782230831000},"score":1,"resource":{"primary":{"URL":"http:\/\/insight.jci.org\/articles\/view\/202443"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,23]]},"references-count":0,"alternative-id":["10.1172\/jci.insight.202443"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.202443","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,23]]}}}