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Trophoblasts remodel the surrounding extracellular matrix through the secretion of matrix metalloproteinases (MMPs). Maternal obesity and diabetes mellitus can negatively impact fetal development and may impair trophoblast function. We sought to model the impact of metabolic stress on STB function by examining MMP and hormone secretion. The BeWo CTB cell line was syncytialized to STB\u2010like cells with forskolin. Cell morphology was examined by electron microscopy and immunofluorescence; phenotype was further assessed by ELISA and RT\u2010qPCR. STBs were exposed to a metabolic stress cocktail (MetaC: 30\u2005mM glucose, 10\u2005nM insulin, and 0.1\u2005mM palmitic acid). BeWo syncytialization was demonstrated by increased secretion of HCG\u03b2 and progesterone, elevated syncytin gene expression (<jats:italic>ERVW\u20101<\/jats:italic> and <jats:italic>ERVFRD\u20101<\/jats:italic>), loss of tight junctions, and increased surface microvilli. MetaC strongly suppressed syncytin gene expression (<jats:italic>ERVW\u20101<\/jats:italic> and <jats:italic>ERVFRD\u20101<\/jats:italic>), suppressed HCG\u03b2 and progesterone secretion, and altered both MMP\u20109 and MMP\u20102 production. Metabolic stress modeling diabetes and obesity altered BeWo STB hormone and MMP production <jats:italic>in\u2005vitro<\/jats:italic>.<\/jats:p>","DOI":"10.1002\/cbic.202300410","type":"journal-article","created":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T11:05:29Z","timestamp":1696590329000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Impact of Metabolic Stress on BeWo Syncytiotrophoblast Function**"],"prefix":"10.1002","volume":"24","author":[{"given":"Lisa M.","family":"Rogers","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases Department of Medicine Indiana University School of Medicine  545 Barnhill Dr., EH 305 Indianapolis IN 46202 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa","family":"Huggins","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Department of Medicine Vanderbilt University Medical Center  Nashville TN 37232 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan S.","family":"Doster","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Department of Medicine Department of Microbiology and Immunology University of Louisville  Louisville KY 40202 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel I.","family":"Omage","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Department of Medicine Vanderbilt University Medical Center  Nashville TN 37232 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Gaddy","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Department of Medicine Vanderbilt University Medical Center  Nashville TN 37232 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Eastman","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Vanderbilt University Medical Center  Nashville TN 37232 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4587-6121","authenticated-orcid":false,"given":"David M.","family":"Aronoff","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Department of Medicine Indiana University School of Medicine  545 Barnhill Dr., EH 305 Indianapolis IN 46202 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,24]]},"reference":[{"key":"e_1_2_10_1_1","unstructured":"\u00a0"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03104-6"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1997.273.5.C1596"},{"key":"e_1_2_10_4_1","first-page":"297","volume":"94","author":"Hamilton W. 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