IL-33 and soluble ST2 in follicular fluid are associated with premature ovarian insufficiency

BackgroundPremature ovarian insufficiency (POI) is a common reproductive disease that is associated with chronic inflammation in ovaries. Interleukin 33 (IL-33) is a pro-inflammatory IL-1 family cytokine, and functions as an alarmin reflecting inflammatory reaction. Our study aimed to investigate le...

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Main Authors: Maoxing Tang, Xuedong Sun, Ping Li, Weifen Deng, Xi Zhan, Peng Sun, Yuhua Shi
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2024.1463371/full
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author Maoxing Tang
Xuedong Sun
Ping Li
Weifen Deng
Xi Zhan
Peng Sun
Yuhua Shi
author_facet Maoxing Tang
Xuedong Sun
Ping Li
Weifen Deng
Xi Zhan
Peng Sun
Yuhua Shi
author_sort Maoxing Tang
collection DOAJ
description BackgroundPremature ovarian insufficiency (POI) is a common reproductive disease that is associated with chronic inflammation in ovaries. Interleukin 33 (IL-33) is a pro-inflammatory IL-1 family cytokine, and functions as an alarmin reflecting inflammatory reaction. Our study aimed to investigate levels of IL-33 and its soluble receptor (sST2) in both follicular fluid (FF) and paired serum during different stages of POI, and evaluate their predictive potentials for POI. Furthermore, we attempted to determine whether IL-33 and sST2 were associated with embryo quality.MethodsA total of 148 women, including 50 patients with biochemical POI (bPOI) (10 IU/L < follicle-stimulating hormone (FSH) ≤ 25 IU/L), 46 patients with POI (25 IU/L<FSH ≤ 40 IU/L) and 52 age-matched control women with normal ovarian reserve were involved in this study. FF and paired serum were collected from these women. IL-33 and sST2 were measured using quantitative sandwich enzyme-linked immunosorbent assay.ResultsFF IL-33 levels were significantly increased in bPOI and POI patients compared to controls. They exhibited positive associations with FSH and luteinizing hormone (LH), whereas negative correlations with anti-Müllerian hormone (AMH), estradiol (E2), testosterone (T) and antral follicle count (AFC). Receiver operating characteristic (ROC) curve analysis showed that for POI prediction, FF IL-33 had a better predictive accuracy (AUC 0.901) with high sensitivity (82.61%) and good specificity (84.62%) than those for bPOI prediction. IL-33 levels in paired serum did not differ among three groups. Regarding sST2, its levels in FF declined with POI progression. Contrarily, they showed negative associations with FSH and LH, but positive correlations with AMH, E2, T and AFC. ROC analysis revealed that FF sST2 had comparatively weak potentials for both bPOI and POI prediction compared to those of FF IL-33. Similarly, there was no significant alteration of sST2 in paired serum among three groups. Additionally, Spearman’s correlation analysis revealed that FF IL-33 levels were negatively associated with the rates of Day-3 good-quality embryos (r=-0.206, P=0.012), whereas FF sST2 did not.ConclusionOur study revealed an increased abundance of FF IL-33, whereas an sST2 deficiency with POI development. This implies that IL-33 and sST2 levels might be associated with the development of POI.
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spelling doaj-art-0aa67757ddf548199ff771faf3c98f6b2025-08-20T02:19:21ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922024-12-011510.3389/fendo.2024.14633711463371IL-33 and soluble ST2 in follicular fluid are associated with premature ovarian insufficiencyMaoxing Tang0Xuedong Sun1Ping Li2Weifen Deng3Xi Zhan4Peng Sun5Yuhua Shi6Department of Reproductive Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Reproductive Medicine, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, ChinaReproductive Medicine Centre, Shenzhen Hengsheng Hospital, Shenzhen, ChinaDepartment of Reproductive Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, ChinaDepartment of Reproductive Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, ChinaDepartment of Obstetrics and Gynecology, Center for Reproductive Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaBackgroundPremature ovarian insufficiency (POI) is a common reproductive disease that is associated with chronic inflammation in ovaries. Interleukin 33 (IL-33) is a pro-inflammatory IL-1 family cytokine, and functions as an alarmin reflecting inflammatory reaction. Our study aimed to investigate levels of IL-33 and its soluble receptor (sST2) in both follicular fluid (FF) and paired serum during different stages of POI, and evaluate their predictive potentials for POI. Furthermore, we attempted to determine whether IL-33 and sST2 were associated with embryo quality.MethodsA total of 148 women, including 50 patients with biochemical POI (bPOI) (10 IU/L < follicle-stimulating hormone (FSH) ≤ 25 IU/L), 46 patients with POI (25 IU/L<FSH ≤ 40 IU/L) and 52 age-matched control women with normal ovarian reserve were involved in this study. FF and paired serum were collected from these women. IL-33 and sST2 were measured using quantitative sandwich enzyme-linked immunosorbent assay.ResultsFF IL-33 levels were significantly increased in bPOI and POI patients compared to controls. They exhibited positive associations with FSH and luteinizing hormone (LH), whereas negative correlations with anti-Müllerian hormone (AMH), estradiol (E2), testosterone (T) and antral follicle count (AFC). Receiver operating characteristic (ROC) curve analysis showed that for POI prediction, FF IL-33 had a better predictive accuracy (AUC 0.901) with high sensitivity (82.61%) and good specificity (84.62%) than those for bPOI prediction. IL-33 levels in paired serum did not differ among three groups. Regarding sST2, its levels in FF declined with POI progression. Contrarily, they showed negative associations with FSH and LH, but positive correlations with AMH, E2, T and AFC. ROC analysis revealed that FF sST2 had comparatively weak potentials for both bPOI and POI prediction compared to those of FF IL-33. Similarly, there was no significant alteration of sST2 in paired serum among three groups. Additionally, Spearman’s correlation analysis revealed that FF IL-33 levels were negatively associated with the rates of Day-3 good-quality embryos (r=-0.206, P=0.012), whereas FF sST2 did not.ConclusionOur study revealed an increased abundance of FF IL-33, whereas an sST2 deficiency with POI development. This implies that IL-33 and sST2 levels might be associated with the development of POI.https://www.frontiersin.org/articles/10.3389/fendo.2024.1463371/fullpremature ovarian insufficiencyIL-33soluble ST2inflammationpredictorovarian reserve
spellingShingle Maoxing Tang
Xuedong Sun
Ping Li
Weifen Deng
Xi Zhan
Peng Sun
Yuhua Shi
IL-33 and soluble ST2 in follicular fluid are associated with premature ovarian insufficiency
Frontiers in Endocrinology
premature ovarian insufficiency
IL-33
soluble ST2
inflammation
predictor
ovarian reserve
title IL-33 and soluble ST2 in follicular fluid are associated with premature ovarian insufficiency
title_full IL-33 and soluble ST2 in follicular fluid are associated with premature ovarian insufficiency
title_fullStr IL-33 and soluble ST2 in follicular fluid are associated with premature ovarian insufficiency
title_full_unstemmed IL-33 and soluble ST2 in follicular fluid are associated with premature ovarian insufficiency
title_short IL-33 and soluble ST2 in follicular fluid are associated with premature ovarian insufficiency
title_sort il 33 and soluble st2 in follicular fluid are associated with premature ovarian insufficiency
topic premature ovarian insufficiency
IL-33
soluble ST2
inflammation
predictor
ovarian reserve
url https://www.frontiersin.org/articles/10.3389/fendo.2024.1463371/full
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AT weifendeng il33andsolublest2infollicularfluidareassociatedwithprematureovarianinsufficiency
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