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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Reproduction
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1525392
This article is part of the Research Topic Ovarian Aging: Pathophysiology and Recent Development of Maintaining Ovarian Reserve, Volume IV View all articles

Proximity extension assay revealed novel inflammatory biomarkers for follicular development and ovarian function: A prospective controlled study combining serum and follicular fluid

Provisionally accepted
Chong Wang Chong Wang *Ying Feng Ying Feng Yu Chen Yu Chen Xianhua Lin Xianhua Lin Xiang-Juan Li Xiang-Juan Li
  • Hangzhou Women’s Hospital, Hangzhou, China

The final, formatted version of the article will be published soon.

    Many components in follicular fluid (FF), such as peptide hormones, cytokines, and steroids, undergo dynamic changes during folliculogenesis and have important roles in follicular development. Because systemic inflammation also contributes to diminished ovarian reserve (DOR) in previous studies, do certain serum/FF inflammatory biomarkers affect both follicular development and ovarian function?Serum samples from the menstruation phase (n=26), serum samples from the ovulation phase (n=26), FF samples of mature oocytes (n=26) and FF samples of immature oocytes (n=10) were collected. Olink proteomic proximity extension assay (PEA) technology was used to compare the differentially expressed proteins (DEPs), and patients were divided into two subgroups-the normal ovarian reserve (NOR) group and the DOR group-for further bioinformatics analysis and verification by enzyme-linked immunosorbent assay (ELISA). Sixteen DEPs were detected between the mature group and the immature group (FF), and 11 DEPs were detected between the ovulation group and the menstruation group (serum). Further subdivision of the ovarian reserve subgroups revealed 22 DEPs in FF and 3 DEPs in serum. Among all four comparisons, only the expression of oncostatin M (OSM) significantly differed.The OSM signalling pathway, the IL-10 anti-inflammatory signalling pathway, and the PI3K-Akt signalling pathway are three notable pathways involved in affecting ovarian reserve capacity according to bioinformatics analysis. In addition, the concentration of oestradiol on the hCG day was slightly but positively correlated with OSM (r=0.457, P=0.029). A significantly greater level of OSM (5.41 ± 2.65 vs. 3.94 ± 1.23 pg/mL, P=0.007) was detected in the serum of NOR patients via ELISA verification, and the sensitivity and specificity of ovarian reserve division were 50.00% and 83.33%, respectively. This study proposed that immunological changes assessed by PEA technology affect ovarian function in humans and that OSM may serve as a potential inflammatory biomarker for ovarian function in serum, thus revealing alterations in FF.

    Keywords: Follicular development, Ovarian function, proximity extension assay, Follicular Fluid, Serum

    Received: 09 Nov 2024; Accepted: 14 Jan 2025.

    Copyright: © 2025 Wang, Feng, Chen, Lin and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Chong Wang, Hangzhou Women’s Hospital, Hangzhou, China

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