{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:48:22Z","timestamp":1790876902508,"version":"4.1.0"},"reference-count":84,"publisher":"The Endocrine Society","issue":"6","license":[{"start":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T00:00:00Z","timestamp":1615334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"BBSRC","doi-asserted-by":"publisher","award":["BB\/R017522\/1"],"award-info":[{"award-number":["BB\/R017522\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"name":"QR-GCRF"},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2016\/22790-1"],"award-info":[{"award-number":["2016\/22790-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2018\/14137-1"],"award-info":[{"award-number":["2018\/14137-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The molecular interactions between the maternal environment and the developing embryo are key for early pregnancy success and are influenced by factors such as maternal metabolic status. Our understanding of the mechanism(s) through which these individual nutritional stressors alter endometrial function and the in utero environment for early pregnancy success is, however, limited. Here we report, for the first time, the use of an endometrium-on-a-chip microfluidics approach to produce a multicellular endometrium in vitro. Isolated endometrial cells (epithelial and stromal) from the uteri of nonpregnant cows in the early luteal phase (Days 4-7) were seeded in the upper chamber of the device (epithelial cells; 4-6 \u00d7 104 cells\/mL) and stromal cells seeded in the lower chamber (1.5-2 \u00d7 104 cells\/mL). Exposure of cells to different concentrations of glucose (0.5, 5.0, or 50 mM) or insulin (Vehicle, 1 or 10 ng\/mL) was performed at a flow rate of 1 \u00b5L\/minute for 72 hours. Quantitative differences in the cellular transcriptome and the secreted proteome of in vitro\u2013derived uterine luminal fluid were determined by RNA-sequencing and tandem mass tagging mass spectrometry, respectively. High glucose concentrations altered 21 and 191 protein-coding genes in epithelial and stromal cells, respectively (P\u2005&amp;lt;\u2005.05), with a dose-dependent quantitative change in the protein secretome (1 and 23 proteins). Altering insulin concentrations resulted in limited transcriptional changes including transcripts for insulin-like binding proteins that were cell specific but altered the quantitative secretion of 196 proteins. These findings highlight 1 potential mechanism by which changes to maternal glucose and insulin alter uterine function.<\/jats:p>","DOI":"10.1210\/endocr\/bqab054","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T11:37:10Z","timestamp":1615462630000},"source":"Crossref","is-referenced-by-count":41,"title":["Endometrium On-a-Chip Reveals Insulin- and Glucose-induced Alterations in the Transcriptome and Proteomic Secretome"],"prefix":"10.1210","volume":"162","author":[{"given":"Tiago H C","family":"De Bem","sequence":"first","affiliation":[{"name":"Discovery and Translational Sciences Department, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, UK"},{"name":"Departamento de Medicina Veterin\u00e1ria, Faculdade de Zootecnia e Engenharia de Alimentos, Universidade de S\u00e3o Paulo, Pirassununga, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haidee","family":"Tinning","sequence":"additional","affiliation":[{"name":"Discovery and Translational Sciences Department, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elton J R","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"LeedsOmics, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dapeng","family":"Wang","sequence":"additional","affiliation":[{"name":"LeedsOmics, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3539-9643","authenticated-orcid":false,"given":"Niamh","family":"Forde","sequence":"additional","affiliation":[{"name":"Discovery and Translational Sciences Department, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, UK"},{"name":"LeedsOmics, University of Leeds, Leeds, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2021,3,10]]},"reference":[{"key":"2021121716525204100_CIT0001","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1111\/j.1439-0531.2008.01230.x","article-title":"Consequences of in vitro culture conditions on embryo development and quality","volume":"43","author":"Rizos","year":"2008","journal-title":"Reprod Domest Anim."},{"issue":"2","key":"2021121716525204100_CIT0002","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1002\/mrd.1153","article-title":"Consequences of bovine oocyte maturation, fertilization or early embryo development in vitro versus in vivo: implications for blastocyst yield and blastocyst quality","volume":"61","author":"Rizos","year":"2002","journal-title":"Mol Reprod Dev."},{"issue":"1","key":"2021121716525204100_CIT0003","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.theriogenology.2016.04.060","article-title":"Maternal-embryo interaction in the bovine oviduct: Evidence from in vivo and in vitro studies","volume":"86","author":"Maillo","year":"2016","journal-title":"Theriogenology."},{"issue":"2","key":"2021121716525204100_CIT0004","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1071\/RD19389","article-title":"Role of extracellular vesicles during oocyte maturation and early embryo development","volume":"32","author":"de \u00c1vila","year":"2019","journal-title":"Reprod Fertil Dev."},{"issue":"5","key":"2021121716525204100_CIT0005","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1095\/biolreprod.116.143503","article-title":"Extracellular vesicles in the intrauterine environment: challenges and potential functions","volume":"95","author":"Nguyen","year":"2016","journal-title":"Biol Reprod."},{"issue":"5","key":"2021121716525204100_CIT0006","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1017\/S2040174417000733","article-title":"Epigenetics and DOHaD: from basics to birth and beyond","volume":"8","author":"Bianco-Miotto","year":"2017","journal-title":"J Dev Orig Health Dis."},{"issue":"1","key":"2021121716525204100_CIT0007","first-page":"R39","article-title":"Early sex-dependent differences in response to environmental stress","volume":"155","author":"P\u00e9rez-Cerezales","year":"2018","journal-title":"Reproduction."},{"key":"2021121716525204100_CIT0008","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1093\/biolre\/iox135","article-title":"Effect of lactation on conceptus-maternal interactions at the initiation of implantation in cattle: I. 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