Hypothalamic Inflammation as a Critical Link Between Metabolic Dysfunction and Impaired Endometrial Receptivity in Obese Polycystic Ovary Syndrome.
Obese polycystic ovary syndrome (PCOS) involves insulin resistance (IR) and impaired endometrial receptivity, potentially driven by hypothalamic inflammation. We investigated if inhibiting the hypothalamic Toll-like receptor 4 (TLR4)/IκB kinase β (IKKβ) pathway could ameliorate IR and improve endome...
| Publicado en: | Physiological Research Vol. 75; no. 3; pp. 485 - 498 |
|---|---|
| Autores principales: | , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Institute of Physiology, Academy of Sciences of the Czech Republic
Jun2026
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=195320571&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 195320571 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 08628408 1CVW jtl: Physiological Research issn: 08628408 maglogo: N pubinfo: dt: Jun2026 vid: 75 iid: 3 pid: 24634 pub: Institute of Physiology, Academy of Sciences of the Czech Republic artinfo: ui: 195320571 10.33549/physiolres.935770 195320571 ppf: 485 ppct: 13 formats: fmt: @attributes: type: P tig: atl: Hypothalamic Inflammation as a Critical Link Between Metabolic Dysfunction and Impaired Endometrial Receptivity in Obese Polycystic Ovary Syndrome. aug: au: SUN, Chang HAN, Yapeng PAN, Zimeng LI, Jing CHENG, Xianzhuo SUN, Miao WANG, Ying KUANG, Hongying affil: Heilongjiang University of Chinese Medicine, Harbin, China. sug: ab: Obese polycystic ovary syndrome (PCOS) involves insulin resistance (IR) and impaired endometrial receptivity, potentially driven by hypothalamic inflammation. We investigated if inhibiting the hypothalamic Toll-like receptor 4 (TLR4)/IκB kinase β (IKKβ) pathway could ameliorate IR and improve endometrial receptivity in an obese PCOS rat model. An obese PCOS rat model was established using letrozole and high-fat diet. Rats were divided into control, PCOS, and three intervention groups: PCOS + intracerebroventricular (i.c.v.) TAK242 (central TLR4 inhibitor), PCOS + intraperitoneal (i.p.) TAK242 (systemic inhibitor), and PCOS + Metformin. We assessed hypothalamic inflammation (TLR4/IKKβ pathway), metabolic parameters (body weight, OGTT, ITT, HOMA-IR), systemic inflammation, and reproductive phenotypes. Endometrial receptivity was evaluated at pregnancy day 6 by uterine morphology, histology, pinopode development (SEM), and receptivity markers (BMP2, VEGF, IGFBP-1). The obese PCOS model successfully induced hypothalamic inflammation (activated TLR4/IKKβ pathway), systemic inflammation, profound IR, and impaired endometrial receptivity (poor decidualization, sparse pinopodes, suppressed receptivity markers). Central (i.c.v.) TAK242 administration was most effective, significantly suppressing the hypothalamic TLR4/IKKβ pathway, attenuating weight gain, normalizing insulin sensitivity, and, critically, restoring endometrial receptivity. Metformin also improved IR and receptivity, but was less potent at inhibiting the hypothalamic TLR4/IKKβ pathway. Systemic (i.p.) TAK242 showed the least efficacy, particularly on metabolic and endometrial outcomes. Hypothalamic inflammation (TLR4/IKKβ pathway) appears to be a critical mechanism linking IR and impaired endometrial receptivity in obese PCOS. Targeted central inhibition was more effective than systemic inhibition, suggesting this pathway is a novel therapeutic target. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|