{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T22:39:33Z","timestamp":1785191973935,"version":"3.55.0"},"reference-count":42,"publisher":"The Endocrine Society","issue":"6","license":[{"start":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T00:00:00Z","timestamp":1744934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82104923"],"award-info":[{"award-number":["82104923"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101777"],"award-info":[{"award-number":["82101777"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Maintaining normal thyroid function is crucial in pregnancy, and the thyroid hormone signaling pathway is involved in embryo implantation. However, the regulation of iodothyronine deiodinase 2 (DIO2), which is the central hub controlling thyroid hormone signaling, and the intracellular pathway activated by triiodothyronine (T3) binding to the thyroid hormone receptor (THR) in endometrial cells, remains unclear. Here, we demonstrate that DIO2 expression increases in endometrium during the establishment of endometrial receptivity and is involved in this process. Iopanoic acid inhibition of DIO2 in vivo can cause a delayed receptive state. In vitro adhesion models have consistently confirmed that knocking down DIO2 in epithelial cells inhibited receptivity establishment. Membrane lipidomics was performed to explore how DIO2 regulates the morphological transformation of endometrial epithelial cells. We found that the deletion of Dio2 inhibited the increase in the degree of lipid unsaturation, which subsequently decreased membrane fluidity. Transcriptomics analysis was employed to explore the downstream target gene of T3\u2013THR signaling mediated by Dio2-mediated T3\u2013THR signaling, and Scd1 is confirmed as the direct target gene of THR in endometrial epithelial cells. These data reveal that DIO2 could regulate lipid metabolism by targeting Scd1 through the T3\u2013THR signaling pathway, thereby modifying membrane fluidity of endometrial epithelial cells and promoting cell morphological transformation to establish endometrial receptivity. These findings contribute to filling the gap in downstream pathways activated by T3\u2013THR signaling in endometrial cells and provide insights into the new therapeutics, prediagnosis, and preventive strategies for the derailment of endometrial receptivity and subsequently adverse \u201cripple effect\u201d including infertility.<\/jats:p>","DOI":"10.1210\/endocr\/bqaf070","type":"journal-article","created":{"date-parts":[[2025,4,19]],"date-time":"2025-04-19T00:59:59Z","timestamp":1745024399000},"source":"Crossref","is-referenced-by-count":2,"title":["T3\u2013THR Signaling Governed by DIO2 Contributes to Endometrial Receptivity by Regulating Epithelial Cell Membrane Fluidity"],"prefix":"10.1210","volume":"166","author":[{"given":"Rui","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Basic Medicine, Chongqing Medical University , Chongqing 400016 ,","place":["P.R. China"]},{"name":"Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, Chongqing Medical University , Chongqing 400016 ,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyu","family":"Peng","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Chongqing Medical University , Chongqing 400016 ,","place":["P.R. China"]},{"name":"Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, Chongqing Medical University , Chongqing 400016 ,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taihang","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Chongqing Medical University , Chongqing 400016 ,","place":["P.R. China"]},{"name":"Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, Chongqing Medical University , Chongqing 400016 ,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqing","family":"Liu","sequence":"additional","affiliation":[{"name":"Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, Chongqing Medical University , Chongqing 400016 ,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlin","family":"He","sequence":"additional","affiliation":[{"name":"Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, Chongqing Medical University , Chongqing 400016 ,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Mu","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Chongqing Medical University , Chongqing 400016 ,","place":["P.R. China"]},{"name":"Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, Chongqing Medical University , Chongqing 400016 ,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Chen","sequence":"additional","affiliation":[{"name":"Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, Chongqing Medical University , Chongqing 400016 ,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rufei","family":"Gao","sequence":"additional","affiliation":[{"name":"Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, Chongqing Medical University , Chongqing 400016 ,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxiong","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Chongqing Medical University , Chongqing 400016 ,","place":["P.R. China"]},{"name":"Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, Chongqing Medical University , Chongqing 400016 ,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixian","family":"Wen","sequence":"additional","affiliation":[{"name":"Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, Chongqing Medical University , Chongqing 400016 ,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5744-8872","authenticated-orcid":false,"given":"Yanqing","family":"Geng","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Chongqing Medical University , Chongqing 400016 ,","place":["P.R. China"]},{"name":"Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, Chongqing Medical University , Chongqing 400016 ,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,4,18]]},"reference":[{"key":"2025050903564310600_bqaf070-B1","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.pharmthera.2017.02.012","article-title":"New insights into thyroid hormone action","volume":"173","author":"Mendoza","year":"2017","journal-title":"Pharmacol Ther"},{"issue":"9","key":"2025050903564310600_bqaf070-B2","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/S2213-8587(18)30028-7","article-title":"Clinical aspects of thyroid function during ageing","volume":"6","author":"Chaker","year":"2018","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"3","key":"2025050903564310600_bqaf070-B3","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1089\/thy.2016.0457","article-title":"2017 guidelines of the American thyroid association for the diagnosis and management of thyroid disease during pregnancy and the postpartum","volume":"27","author":"Alexander","year":"2017","journal-title":"Thyroid"},{"issue":"7","key":"2025050903564310600_bqaf070-B4","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/S2213-8587(17)30402-3","article-title":"Autoimmune thyroid disease during pregnancy","volume":"6","author":"De Leo","year":"2018","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"1","key":"2025050903564310600_bqaf070-B5","doi-asserted-by":"crossref","first-page":"9914009","DOI":"10.1155\/2021\/9914009","article-title":"The type 2 deiodinase Thr92Ala polymorphism is associated with higher body mass Index and fasting glucose levels: a systematic review and meta-analysis","volume":"2021","author":"Wang","year":"2021","journal-title":"Biomed Res Int"},{"key":"2025050903564310600_bqaf070-B6","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/978-1-4939-7902-8_8","article-title":"The deiodinase trio and thyroid hormone signaling","volume":"1801","author":"Bianco","year":"2018","journal-title":"Methods Mol Biol"},{"issue":"4","key":"2025050903564310600_bqaf070-B7","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1111\/cen.14817","article-title":"Genetic disorders of thyroid development, hormone biosynthesis and signalling","volume":"97","author":"Moran","year":"2022","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"5","key":"2025050903564310600_bqaf070-B8","doi-asserted-by":"crossref","first-page":"952","DOI":"10.3803\/EnM.2021.1198","article-title":"Deiodinases and the three types of thyroid hormone deiodination reactions","volume":"36","author":"Sabatino","year":"2021","journal-title":"Endocrinol Metab (Seoul)"},{"issue":"19","key":"2025050903564310600_bqaf070-B9","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1056\/NEJMra000763","article-title":"Implantation and the survival of early pregnancy","volume":"345","author":"Norwitz","year":"2001","journal-title":"N Engl J Med"},{"issue":"4","key":"2025050903564310600_bqaf070-B10","doi-asserted-by":"crossref","first-page":"326","DOI":"10.5603\/GP.a2022.0054","article-title":"Implantation of embryos. The way for the improvement of the cumulative life birth rate (CLBR) in the assisted reproductive technology (ART)","volume":"94","author":"Szamatowicz","year":"2023","journal-title":"Ginekol Pol"},{"issue":"2","key":"2025050903564310600_bqaf070-B11","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1093\/humupd\/dmy044","article-title":"Conventional and modern markers of endometrial receptivity: a systematic review and meta-analysis","volume":"25","author":"Craciunas","year":"2019","journal-title":"Hum Reprod Update"},{"issue":"6","key":"2025050903564310600_bqaf070-B12","doi-asserted-by":"crossref","first-page":"3915","DOI":"10.21037\/qims-22-705","article-title":"Using 2D\/3D ultrasound observation of endometrial thickness, endometrial volume, and blood flow changes to predict the outcome of frozen embryo transfer cycles: a prospective study","volume":"13","author":"Liu","year":"2023","journal-title":"Quant Imaging Med Surg"},{"key":"2025050903564310600_bqaf070-B13","doi-asserted-by":"crossref","first-page":"596324","DOI":"10.3389\/fendo.2020.596324","article-title":"Alterations in epithelial cell polarity during endometrial receptivity: a systematic review","volume":"11","author":"Whitby","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"2025050903564310600_bqaf070-B14","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1093\/humupd\/dmy035","article-title":"The role of mesenchymal-epithelial transition in endometrial function","volume":"25","author":"Owusu-Akyaw","year":"2019","journal-title":"Hum Reprod Update"},{"issue":"1","key":"2025050903564310600_bqaf070-B15","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.fertnstert.2010.06.079","article-title":"Thyroid-stimulating hormone receptor and thyroid hormone receptors are involved in human endometrial physiology","volume":"95","author":"Aghajanova","year":"2011","journal-title":"Fertil Steril"},{"issue":"12","key":"2025050903564310600_bqaf070-B16","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1089\/thy.2021.0638","article-title":"Kisspeptin treatment restores ovarian function in rats with hypothyroidism","volume":"32","author":"de Oliveira","year":"2022","journal-title":"Thyroid"},{"issue":"9","key":"2025050903564310600_bqaf070-B17","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.3390\/ani11092636","article-title":"Hypothyroidism affects uterine function via the modulation of prostaglandin signaling","volume":"11","author":"Kowalczyk-Zieba","year":"2021","journal-title":"Animals (Basel)"},{"issue":"7","key":"2025050903564310600_bqaf070-B18","doi-asserted-by":"crossref","first-page":"2704","DOI":"10.1210\/en.2014-1015","article-title":"Regulation and function of deiodinases during decidualization in female mice","volume":"155","author":"Deng","year":"2014","journal-title":"Endocrinology"},{"issue":"3","key":"2025050903564310600_bqaf070-B19","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1002\/rmb2.12280","article-title":"Uterine receptivity, embryo attachment, and embryo invasion: multistep processes in embryo implantation","volume":"18","author":"Fukui","year":"2019","journal-title":"Reprod Med Biol"},{"issue":"24","key":"2025050903564310600_bqaf070-B20","doi-asserted-by":"crossref","first-page":"4813","DOI":"10.1007\/s00018-019-03245-8","article-title":"Epigenetic control of embryo-uterine crosstalk at peri-implantation","volume":"76","author":"Kong","year":"2019","journal-title":"Cell Mol Life Sci"},{"issue":"4","key":"2025050903564310600_bqaf070-B21","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.jphs.2023.09.006","article-title":"Regulatory action of PGRMC1 on cyclic AMP-mediated COX2 expression in human endometrial cells","volume":"153","author":"Tsuru","year":"2023","journal-title":"J Pharmacol Sci"},{"issue":"4","key":"2025050903564310600_bqaf070-B22","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.ogc.2023.09.002","article-title":"Progress on the endometrium","volume":"50","author":"Frankfurter","year":"2023","journal-title":"Obstet Gynecol Clin North Am"},{"key":"2025050903564310600_bqaf070-B23","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.semcdb.2014.05.005","article-title":"Cadence of procreation: orchestrating embryo-uterine interactions","volume":"34","author":"Cha","year":"2014","journal-title":"Semin Cell Dev Biol"},{"issue":"10","key":"2025050903564310600_bqaf070-B24","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.1007\/s43032-022-00902-5","article-title":"Delayed implantation induced by letrozole in mice","volume":"29","author":"Wang","year":"2022","journal-title":"Reprod Sci"},{"issue":"12","key":"2025050903564310600_bqaf070-B25","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1242\/dev.129.12.2879","article-title":"Cytosolic phospholipase A2alpha is crucial [correction of A2alpha deficiency is crucial] for \u2018on-time\u2019 embryo implantation that directs subsequent development","volume":"129","author":"Song","year":"2002","journal-title":"Development (Cambridge, England)"},{"issue":"7038","key":"2025050903564310600_bqaf070-B26","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nature03505","article-title":"LPA3-mediated lysophosphatidic acid signalling in embryo implantation and spacing","volume":"435","author":"Ye","year":"2005","journal-title":"Nature"},{"issue":"6","key":"2025050903564310600_bqaf070-B27","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1093\/humupd\/dmad016","article-title":"The pathophysiological role of estrogens in the initial stages of pregnancy: molecular mechanisms and clinical implications for pregnancy outcome from the periconceptional period to end of the first trimester","volume":"29","author":"Parisi","year":"2023","journal-title":"Hum Reprod Update"},{"issue":"1","key":"2025050903564310600_bqaf070-B28","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1242\/jcs.175943","article-title":"Embryo-epithelium interactions during implantation at a glance","volume":"130","author":"Aplin","year":"2017","journal-title":"J Cell Sci"},{"issue":"1","key":"2025050903564310600_bqaf070-B29","doi-asserted-by":"crossref","first-page":"e1010018","DOI":"10.1371\/journal.pgen.1010018","article-title":"Shp2 in uterine stromal cells critically regulates on time embryo implantation and stromal decidualization by multiple pathways during early pregnancy","volume":"18","author":"Cheng","year":"2022","journal-title":"PLoS Genet"},{"issue":"5","key":"2025050903564310600_bqaf070-B30","doi-asserted-by":"crossref","first-page":"749","DOI":"10.3390\/jpm13050749","article-title":"Review of endometrial receptivity array: a personalized approach to embryo transfer and its clinical applications","volume":"13","author":"Rubin","year":"2023","journal-title":"J Pers Med"},{"issue":"4","key":"2025050903564310600_bqaf070-B31","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.fertnstert.2019.02.009","article-title":"What exactly is endometrial receptivity?","volume":"111","author":"Lessey","year":"2019","journal-title":"Fertil Steril"},{"issue":"2","key":"2025050903564310600_bqaf070-B32","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.tem.2019.11.008","article-title":"Uterine luminal epithelium as the transient gateway for embryo implantation","volume":"31","author":"Ye","year":"2020","journal-title":"Trends Endocrinol Metab"},{"key":"2025050903564310600_bqaf070-B33","doi-asserted-by":"crossref","first-page":"110644","DOI":"10.1016\/j.mce.2019.110644","article-title":"Pinopodes: recent advancements, current perspectives, and future directions","volume":"501","author":"Quinn","year":"2020","journal-title":"Mol Cell Endocrinol"},{"issue":"21","key":"2025050903564310600_bqaf070-B34","doi-asserted-by":"crossref","first-page":"11860","DOI":"10.18632\/aging.205142","article-title":"Lipid reprogramming induced by the NNMT-ABCA1 axis enhanced membrane fluidity to promote endometrial cancer progression","volume":"15","author":"Wen","year":"2023","journal-title":"Aging (Albany NY)"},{"issue":"1","key":"2025050903564310600_bqaf070-B35","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1146\/annurev-physiol-020518-114444","article-title":"Phospholipid remodeling in physiology and disease","volume":"81","author":"Wang","year":"2019","journal-title":"Annu Rev Physiol"},{"issue":"11","key":"2025050903564310600_bqaf070-B36","doi-asserted-by":"crossref","first-page":"eaax7525","DOI":"10.1126\/sciadv.aax7525","article-title":"Phospholipid remodeling is critical for stem cell pluripotency by facilitating mesenchymal-to-epithelial transition","volume":"5","author":"Wu","year":"2019","journal-title":"Sci Adv"},{"issue":"1","key":"2025050903564310600_bqaf070-B37","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1146\/annurev.nutr.24.121803.063211","article-title":"Structure, function, and dietary regulation of delta6, delta5, and delta9 desaturases","volume":"24","author":"Nakamura","year":"2004","journal-title":"Annu Rev Nutr"},{"issue":"2","key":"2025050903564310600_bqaf070-B38","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/s41556-023-01341-3","article-title":"Low-input lipidomics reveals lipid metabolism remodelling during early mammalian embryo development","volume":"26","author":"Zhang","year":"2024","journal-title":"Nat Cell Biol"},{"issue":"1","key":"2025050903564310600_bqaf070-B39","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3390\/ijms22010109","article-title":"Interplay between thyroid hormones and stearoyl-CoA desaturase 1 in the regulation of lipid metabolism in the heart","volume":"22","author":"Olichwier","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"10","key":"2025050903564310600_bqaf070-B40","doi-asserted-by":"crossref","first-page":"8951","DOI":"10.3390\/ijms24108951","article-title":"Stearoyl-CoA desaturase 1 as a therapeutic biomarker: focusing on cancer stem cells","volume":"24","author":"Min","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"7","key":"2025050903564310600_bqaf070-B41","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1016\/j.ymthe.2022.03.015","article-title":"An SCD1-dependent mechanoresponsive pathway promotes HCC invasion and metastasis through lipid metabolic reprogramming","volume":"30","author":"Liu","year":"2022","journal-title":"Molecular Therapy"},{"issue":"2","key":"2025050903564310600_bqaf070-B42","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1002\/hep.29033","article-title":"Functional lipidomics: palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism","volume":"66","author":"Lin","year":"2017","journal-title":"Hepatology (Baltimore, Md)"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/endo\/advance-article-pdf\/doi\/10.1210\/endocr\/bqaf070\/62955354\/bqaf070.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/endo\/article-pdf\/166\/6\/bqaf070\/62955354\/bqaf070.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/endo\/article-pdf\/166\/6\/bqaf070\/62955354\/bqaf070.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T07:57:04Z","timestamp":1746777424000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/doi\/10.1210\/endocr\/bqaf070\/8116265"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,18]]},"references-count":42,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,4,22]]}},"URL":"https:\/\/doi.org\/10.1210\/endocr\/bqaf070","relation":{},"ISSN":["1945-7170"],"issn-type":[{"value":"1945-7170","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,6]]},"published":{"date-parts":[[2025,4,18]]},"article-number":"bqaf070"}}