{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T11:13:41Z","timestamp":1783509221303,"version":"3.55.0"},"reference-count":91,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:p>Gestational diabetes mellitus, a hyperglycemic condition during pregnancy, increases the risk of macrosomia and preterm birth (PTB). Nutrient-sensing pathways, particularly mTOR in placental trophoblast cells (PTCs), promote fetal overgrowth. NF-\u03baB, oxidative stress, and p38 MAPK pathways in fetal membranes and decidua (DEC) contribute to PTB. However, the impact of hyperglycemia on these compartments remains unclear. We hypothesized that hyperglycemia differentially affects these maternal, placental, and fetal membrane interface cells, inducing macrosomia-associated pathways and perturbing homeostasis through different pathophysiological signals. Human PTCs, DECs, and amnion epithelial cells (AECs) were exposed to 50 mM glucose for up to 48 h. Cell markers (ICC), cell cycle (flow cytometry), cytotoxicity (LDH assay), GLUT expression (RT-qPCR), signaling (mTOR, p38 MAPK, and NF-\u03baB by western blot), cytokines (ELISA), and oxidative stress (glutathione assay) were measured. PTCs showed increased mTOR and p38 MAPK activation (P \u2264 0.05), reduced GSH levels and GSH\/GSSG balance (P \u2264 0.05), but maintained GLUT expression. DECs reduced GLUT1\/3 expression (P \u2264 0.01; P \u2264 0.05) with minimal stress and nutrient signaling. Neither cell type showed NF-\u03baB activation. AECs downregulated GLUT1\/3\/11 (P \u2264 0.05\u20130.0001), activated NF-\u03baB (P \u2264 0.01), produced IL-8 (P \u2264 0.01), increased GSH production (P \u2264 0.05), but maintained mTOR signaling and GSH\/GSSG balance. Hyperglycemia induces compartment-specific adaptations across the feto-maternal interface. Placental trophoblasts preserve nutrient transport capacity and nutrient signaling despite redox imbalance. Fetal membranes exhibit inflammatory response, while decidua reduces transport capacity with minimal stress activation. Together, these findings suggest that hyperglycemia may preferentially support fetal growth through trophoblasts while sensitizing decidua and membrane to secondary stressors.<\/jats:p>","DOI":"10.1530\/joe-25-0411","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T10:16:34Z","timestamp":1776334594000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":0,"title":["High glucose exposure induces differential pathophysiological changes in feto-maternal interface cells"],"prefix":"10.1530","volume":"269","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8334-0224","authenticated-orcid":true,"given":"Glenmarie Angelica S","family":"Perias","sequence":"first","affiliation":[{"name":"1"},{"name":"2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula Pereira","family":"Guimaraes","sequence":"additional","affiliation":[{"name":"1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ourlad Alzeus G","family":"Tantengco","sequence":"additional","affiliation":[{"name":"1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie Michelle M","family":"Dalmacio","sequence":"additional","affiliation":[{"name":"2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren S","family":"Richardson","sequence":"additional","affiliation":[{"name":"1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ananth 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