{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T20:02:56Z","timestamp":1792526576149,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Epidemiological studies suggest a link between gestational diabetes mellitus (GDM) and periodontitis. In this context,\n Porphyromonas gingivalis<\/jats:italic>\n (\n Pg<\/jats:italic>\n ) and its byproducts, including lipopolysaccharide (\n Pg<\/jats:italic>\n \u2010LPS), may translocate to the placenta, potentially intensifying pro\u2010inflammatory mechanisms in a hyperglycemic environment. This study aimed to assess the pro\u2010inflammatory simultaneous\u00a0stimulus effect\u00a0of hyperglycemia (HG)\u00a0and\u00a0\n Pg<\/jats:italic>\n \u2010LPS\u00a0in\u00a0human term placental explants.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Fresh placental explants from healthy (\n n<\/jats:italic>\n \u00a0=\u00a010) and GDM (\n n<\/jats:italic>\n \u00a0=\u00a05) pregnant women were stimulated under normoglycemia (NG), hyperglycemia (HG),\n Pg<\/jats:italic>\n \u2010LPS, and a dual stimulus of HG+\n Pg<\/jats:italic>\n \u2010LPS. Both placental explants and culture supernatants were assessed using histology, real\u2010time quantitative polymerase chain reaction (RT\u2010qPCR), Western blot, immunofluorescence, and multiplex immunoassay to analyze histopathological alterations, Toll\u2010like receptor (TLR)\u22122, \u22124, \u22129 mRNA expression, nuclear factor kappa\u2010light\u2010chain\u2010enhancer of activated B cells (NF\u2010\u03baB) phosphorylation and nuclear immunolocalization, NLRP3 inflammasome expression, and pro\u2010inflammatory cytokines (interleukin [IL]\u20106, IL\u20101\u03b2, and tumor necrosis factor [TNF]\u2010\u03b1).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The dual stimulus (HG+\n Pg<\/jats:italic>\n \u2010LPS) increased fibrinoid necrosis (\n p\u00a0<\/jats:italic>\n <\u00a00.05) and upregulated TLR\u20104 mRNA (\n p\u00a0<\/jats:italic>\n <\u00a00.05) expression in placental explants, compared to other experimental conditions. NF\u2010\u03baB phosphorylation and nuclear immunolocalization, NLRP3 inflammasome and IL\u20106, IL\u20101\u03b2, and TNF\u2010\u03b1 mRNA expression increased upon the dual stimulus in healthy and GDM explants (\n p\u00a0<\/jats:italic>\n <\u00a00.05). Additionally, levels of IL\u20106 (\n p\u00a0<\/jats:italic>\n <\u00a00.01), IL\u20101\u03b2 (\n p\u00a0<\/jats:italic>\n <\u00a00.01), and TNF\u2010\u03b1 (\n p\u00a0<\/jats:italic>\n <\u00a00.0001) increased in the supernatant from healthy and GDM explants under the dual stimulus. No differences in cytokine levels were observed between healthy and GDM placental explants under the dual stimulus.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n A hyperglycemic environment amplifies the pro\u2010inflammatory response to\u00a0\n Pg<\/jats:italic>\n \u2010LPS in human placental explants, suggesting that hyperglycemia synergizes with\n Pg<\/jats:italic>\n \u2010LPS in the placenta.\n <\/jats:p>\n <\/jats:sec>\n \n Plain language summary<\/jats:title>\n Bacteria that drive periodontitis, or their products, can enter the bloodstream and reach the placenta. In a high\u2010glucose environment, this exposure can intensify placental inflammation. This study aimed to determine whether exposure to a high\u2010glucose milieu, combined with byproducts of periodontal bacteria, activates inflammatory pathways in the placenta. Our results demonstrate that a high\u2010glucose environment amplifies the inflammatory response to periodontal bacteria in human placentas from both healthy pregnancies and those complicated by gestational diabetes mellitus. These findings advance our understanding of the connection between periodontitis and gestational diabetes mellitus and underscore the role of oral bacterial translocation in placental tissues during pregnancy.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jper.70051","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T13:49:45Z","timestamp":1767188985000},"page":"1257-1270","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Hyperglycemia exacerbates placental inflammation induced by\n Porphyromonas gingivali<\/i>\n s\u2010lipopolysaccharide"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3493-0156","authenticated-orcid":false,"given":"Mar\u00eda Jos\u00e9","family":"Bendek","sequence":"first","affiliation":[{"name":"Faculty of Medicine Doctoral Program in Biomedicine Centre for Biomedical Research and Innovation Universidad de los Andes Santiago 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