{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T17:05:47Z","timestamp":1784739947481,"version":"3.55.0"},"reference-count":82,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["R00 HD098330"],"award-info":[{"award-number":["R00 HD098330"]}]},{"name":"National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["T32 AR080622"],"award-info":[{"award-number":["T32 AR080622"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In brief: Polyendocrine metabolic ovarian syndrome (PMOS) is associated with metabolic, reproductive, and immune dysfunction, yet the mechanisms driving these abnormalities remain unclear. This study identifies Toll-like receptor 4 (TLR4) as a key contributor of PMOS-like pathology in mice, linking gut barrier disruption and endotoxin-associated immune activation to impaired metabolic and reproductive function.<\/jats:p>\n                  <jats:p>Abstract: Polyendocrine metabolic ovarian syndrome (PMOS), formerly termed polycystic ovary syndrome (PCOS), is a reproductive disorder with heterogeneous symptoms and severity. Despite extensive research documenting chronic immune dysfunction as a hallmark of PMOS, the specific mechanisms of immune activation remain poorly understood. Emerging evidence suggests that gut-derived bacterial endotoxins, particularly lipopolysaccharide (LPS), can breach intestinal barriers and trigger systemic inflammation via Toll-like receptor 4 (TLR4). This study examined the role of TLR4 in PMOS-like pathology using a letrozole (LET)-induced mouse model. In LET-treated wild-type female mice, serum LPS and its carrier protein lipopolysaccharide-binding protein (LBP) were elevated compared with LET-treated TLR4\u2013\/\u2013 mice. Additionally, TLR4 deficiency attenuated multiple PMOS-like features, including elevated luteinizing hormone, anovulation, and metabolic dysfunction. The LET-treated TLR4\u2013\/\u2013 mice also preserved estrous cycling and fertility, maintained gut barrier integrity, and reduced inflammatory markers. These findings support TLR4 as an important contributor to multiple features of PMOS-like pathology. This novel work highlights TLR4-mediated inflammation as a potential target for anti-inflammatory treatments in women with PMOS.<\/jats:p>","DOI":"10.1093\/reprod\/xaag081","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T23:17:02Z","timestamp":1782861422000},"source":"Crossref","is-referenced-by-count":0,"title":["Toll-like receptor 4 knockout mice are protected against PMOS-like pathogenesis"],"prefix":"10.1093","volume":"172","author":[{"given":"Kiara","family":"Wiggins","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, School of Biological Sciences, University of California Irvine , Irvine, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zena","family":"Del Mundo","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, School of Biological Sciences, University of California Irvine , Irvine, CA,","place":["United 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