Follicular fluid soluble receptor for advanced glycation end-products (sRAGE): a potential indicator of ovarian reserve
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Updated: May 5, 2026
Collection of Human Follicular Fluid, Follicle Somatic Cells, and Immature Oocytes from Individuals Undergoing In Vitro Fertilization
Published on: October 24, 2025
Zaher Merhi1, Mohamad Irani, Angela D Doswell
1Department of Obstetrics, Gynecology, and Reproductive Sciences (Z.M., A.D.D., J.A.), Division of Reproductive Endocrinology and Infertility, University of Vermont College of Medicine, Burlington, Vermont 05401; and Department of Obstetrics and Gynecology (M.I.), Maimonides Medical Center, Brooklyn, New York 11219.
Context:
The interaction of advanced glycation end-products (AGEs) with their cellular receptor (RAGE) is implicated in the pathogenesis of abnormal ovarian follicular growth. RAGE has a circulating secretory receptor form, soluble RAGE (sRAGE), which neutralizes the action of AGEs and might exert a protective role on the follicular environment.
Objective:
The objective of the study was to investigate whether serum or follicular fluid (FF) sRAGE levels are associated with markers of ovarian reserve.
Design, Setting, And Participants:
Serum anti-Mullerian hormone (AMH) and sRAGE protein levels were correlated in 31 reproductive-aged women. An additional 33 women who underwent oocyte retrieval for in vitro fertilization were enrolled. AMH and its receptor (AMHR-II) mRNA levels were quantified in cumulus granulosa cells and FF sRAGE and AMH protein levels were measured.
Main Outcome Measures:
Granulosa cell AMH and AMHR-II gene expression, serum and FF AMH and sRAGE protein concentration, and number of oocytes retrieved were measured.
Results:
In the serum, sRAGE levels were negatively correlated with body mass index (BMI) (r = -0.5, P < .001) but not with age or serum AMH. The higher the FF sRAGE, the lower the number of international units of gonadotropin needed per cycle independent of age, BMI, or day 3 FSH level (r = -0.4, P = .04). After adjusting for age, BMI, day 3 FSH, and the total dose of gonadotropins, FF sRAGE predicted the number of oocytes retrieved (R(2) = 0.27, P = .045). FF sRAGE positively correlated with FF AMH levels (r = 0.5, P = .0085). RT-PCR results showed no correlation between the FF sRAGE and AMH or AMHR-II mRNA levels.
Conclusion:
These data support a relationship between FF sRAGE and measures of ovarian reserve. The pathological significance of the harmful inflammatory AGEs in follicular health clearly requires further investigation. Targeting AGEs might offer potential therapeutic options for the treatment of diminished ovarian response.
Insights
Soluble RAGE (sRAGE) in follicular fluid is linked to ovarian reserve markers like AMH and predicts oocyte yield. Targeting AGEs may improve diminished ovarian response treatments.
Area of Science:
- Reproductive Endocrinology
- Ovarian Physiology
- Molecular Biology
Background:
- Advanced glycation end-products (AGEs) and their receptor (RAGE) pathway are implicated in abnormal ovarian follicular growth.
- Soluble RAGE (sRAGE), a circulating form of RAGE, may protect the follicular environment by neutralizing AGEs.
Purpose of the Study:
- To investigate the association between serum and follicular fluid (FF) sRAGE levels and ovarian reserve markers.
- To determine if sRAGE levels correlate with factors influencing ovarian response in women undergoing IVF.
Main Methods:
- Correlated serum anti-Mullerian hormone (AMH) and sRAGE levels in 31 women.
- Quantified AMH and its receptor (AMHR-II) mRNA in granulosa cells and measured FF sRAGE and AMH protein in 33 women undergoing oocyte retrieval.
- Measured gene expression, protein concentrations, and oocyte retrieval numbers.
Main Results:
- Serum sRAGE negatively correlated with BMI but not with age or serum AMH.
- Higher FF sRAGE levels correlated with lower gonadotropin requirements and predicted the number of oocytes retrieved, independent of age, BMI, or FSH.
- FF sRAGE positively correlated with FF AMH levels, but no correlation was found with AMH or AMHR-II mRNA levels.
Conclusions:
- Follicular fluid sRAGE is associated with key measures of ovarian reserve.
- The role of AGEs in follicular health warrants further investigation.
- Targeting AGEs could offer therapeutic strategies for diminished ovarian response.
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