Role of sRAGE in clinical heterogeneity and inflammation in endometriosis patients undergoing IVF; case-control study.

Authors

Neda Emami, Ashraf Moini

Published in

BMC endocrine disorders. Jul 15, 2026. Epub Jul 15, 2026.

Abstract

Endometriosis is a multifactorial, chronic inflammatory disorder that affects a substantial proportion of women during their reproductive years and is frequently associated with pelvic pain and infertility. Accumulating evidence suggests that advanced glycation end products (AGEs), generated through dietary exposure and oxidative stress, may contribute to disease progression by activating the receptor for AGEs (RAGE), thereby promoting inflammatory and fibrotic signaling pathways. Rather than serving as an initiating factor, the AGE-RAGE axis is increasingly recognized as an amplifier of persistent inflammation and lesion persistence in endometriosis. The soluble isoform of RAGE (sRAGE) acts as a circulating decoy receptor that sequesters AGEs and attenuates downstream pro-inflammatory cascades. Although dysregulated sRAGE concentrations have been documented in various metabolic and reproductive conditions, its specific role in endometriosis-particularly within the follicular microenvironment and in relation to inflammatory status-remains incompletely characterized.
In this prospective case-control study, 71 women of reproductive age undergoing controlled ovarian stimulation and oocyte retrieval for in vitro fertilization (IVF) were enrolled. The case group included 40 women with confirmed endometriosis, while 31 women without endometriosis served as controls. Detailed clinical histories were obtained for both groups. Serum and follicular fluid samples were collected, and sRAGE concentrations were quantified using enzyme-linked immunosorbent assay (ELISA).
No significant differences were observed between groups regarding age or body mass index. Both serum and follicular fluid sRAGE concentrations were significantly elevated in women with endometriosis compared with controls (both P < 0.001). Evaluation of clinical heterogeneity demonstrated significantly lower follicular fluid sRAGE levels among endometriosis women with concomitant allergic conditionsnull (P = 0.012). Within the endometriosis cohort, sRAGE concentrations did not vary significantly according to pain severity, including dysmenorrhea, pelvic pain, or dyspareunia. Likewise, no significant associations were identified with thyroid disorders, gastrointestinal disease, adenomyosis, migraine, asthma, diabetes, or multiple sclerosis. Furthermore, sRAGE levels were not correlated with the number of retrieved oocytes or embryos in either group.
Women with endometriosis exhibited significantly elevated serum and follicular fluid sRAGE levels, suggesting altered AGE-RAGE axis activity. However, the absence of association with ovarian response indicates that sRAGE may reflect inflammatory status rather than reproductive outcomes.

PMID:
42458409
Bibliographic data and abstract were imported from PubMed on 16 Jul 2026.

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