The association between metal exposure in follicular fluid and PCOS risk in reproductive-aged women: Mediating Roles of LH/FSH ratio and androgens

The associations between trace elements levels and the risk of polycystic ovary syndrome (PCOS), particularly main contributor and their joint effect, are limited and elusive. In this case-control study, we involved 388 women with PCOS and 465 controls. We measured eighteen (aluminum, titanium, vana...

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Main Authors: Xin Wang, Xueting Lai, Chenke Pan, Tao Yin, Wei Zhu, Xinyue Zhu, Jian Chen, Chunmei Liang, Dongmei Ji
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651325008139
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author Xin Wang
Xueting Lai
Chenke Pan
Tao Yin
Wei Zhu
Xinyue Zhu
Jian Chen
Chunmei Liang
Dongmei Ji
author_facet Xin Wang
Xueting Lai
Chenke Pan
Tao Yin
Wei Zhu
Xinyue Zhu
Jian Chen
Chunmei Liang
Dongmei Ji
author_sort Xin Wang
collection DOAJ
description The associations between trace elements levels and the risk of polycystic ovary syndrome (PCOS), particularly main contributor and their joint effect, are limited and elusive. In this case-control study, we involved 388 women with PCOS and 465 controls. We measured eighteen (aluminum, titanium, vanadium, chromium, manganese, iron, cobalt, copper, zinc, selenium, arsenic, cadmium, barium, mercury, lead, strontium, stannum, thallium) in follicular fluid through inductively coupled plasma–mass spectrometry (ICP-MS). Based on the multi−step statistical analysis including quantile g-computation (Q-gcomp), logistic regression model, orthogonal partial least squares discriminant analysis (OPLS-DA), random forest (RF) model and weighted quantile sum (WQS) regression, the top three essential trace elements among the 18 elements significantly associated with PCOS risk were cobalt (Co), stannum (Sn) and manganese (Mn), the top three heavy metals were lead (Pb), cadmium (Cd) and barium (Ba). The results of the BKMR model showed that mixtures of Pb, Cd and Ba were positively associated with the risk of PCOS, mixtures of Co, Sn and Mn were negatively associated with the risk of PCOS, mixtures of these six trace elements were negatively associated with the risk of PCOS at high concentrations, mixtures of 18 trace elements was negatively associated with the risk of PCOS. It states clearly that exposure to trace elements is associated with a decreased risk of PCOS, with trace essential elements possibly playing a greater role. In addition, we revealed that testosterone was significantly and positively mediating the association between Ba level and the risk of PCOS with mediated proportion of 0.07, testosterone was significantly and negatively mediating the association between Sn level and the risk of PCOS with mediated proportion of 0.14, LH/FSH ratio were significantly and negatively mediating the association between Co, Mn level and the risk of PCOS (with mediated proportion of 0.23 and 0.34, respectively). Our study indicates that eschewing heavy metals and supplementing properly with trace essential elements are conducive to reducing the risk of PCOS.
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spelling doaj-art-7c2684f4e9bd409088b97fed20d8e51b2025-08-20T02:39:35ZengElsevierEcotoxicology and Environmental Safety0147-65132025-07-0130011847310.1016/j.ecoenv.2025.118473The association between metal exposure in follicular fluid and PCOS risk in reproductive-aged women: Mediating Roles of LH/FSH ratio and androgensXin Wang0Xueting Lai1Chenke Pan2Tao Yin3Wei Zhu4Xinyue Zhu5Jian Chen6Chunmei Liang7Dongmei Ji8Department of Ultrasound, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu 322000, China; Department of Obstetrics and Gynecology, the First Affiliated Hospital, Anhui Medical University, No 218 Jixi Road, Hefei, Anhui 230022, ChinaDepartment of Obstetrics and Gynecology, the First Affiliated Hospital, Anhui Medical University, No 218 Jixi Road, Hefei, Anhui 230022, ChinaDepartment of Ultrasound, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu 322000, ChinaDepartment of Obstetrics and Gynecology, the First Affiliated Hospital, Anhui Medical University, No 218 Jixi Road, Hefei, Anhui 230022, ChinaDepartment of Ultrasound, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu 322000, ChinaDepartment of Ultrasound, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu 322000, ChinaDepartment of Ultrasound, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu 322000, China; Correspondence to: Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, Anhui 230022, China.School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, Anhui 230032, China; Corresponding authors.Department of Obstetrics and Gynecology, the First Affiliated Hospital, Anhui Medical University, No 218 Jixi Road, Hefei, Anhui 230022, China; Corresponding authors.The associations between trace elements levels and the risk of polycystic ovary syndrome (PCOS), particularly main contributor and their joint effect, are limited and elusive. In this case-control study, we involved 388 women with PCOS and 465 controls. We measured eighteen (aluminum, titanium, vanadium, chromium, manganese, iron, cobalt, copper, zinc, selenium, arsenic, cadmium, barium, mercury, lead, strontium, stannum, thallium) in follicular fluid through inductively coupled plasma–mass spectrometry (ICP-MS). Based on the multi−step statistical analysis including quantile g-computation (Q-gcomp), logistic regression model, orthogonal partial least squares discriminant analysis (OPLS-DA), random forest (RF) model and weighted quantile sum (WQS) regression, the top three essential trace elements among the 18 elements significantly associated with PCOS risk were cobalt (Co), stannum (Sn) and manganese (Mn), the top three heavy metals were lead (Pb), cadmium (Cd) and barium (Ba). The results of the BKMR model showed that mixtures of Pb, Cd and Ba were positively associated with the risk of PCOS, mixtures of Co, Sn and Mn were negatively associated with the risk of PCOS, mixtures of these six trace elements were negatively associated with the risk of PCOS at high concentrations, mixtures of 18 trace elements was negatively associated with the risk of PCOS. It states clearly that exposure to trace elements is associated with a decreased risk of PCOS, with trace essential elements possibly playing a greater role. In addition, we revealed that testosterone was significantly and positively mediating the association between Ba level and the risk of PCOS with mediated proportion of 0.07, testosterone was significantly and negatively mediating the association between Sn level and the risk of PCOS with mediated proportion of 0.14, LH/FSH ratio were significantly and negatively mediating the association between Co, Mn level and the risk of PCOS (with mediated proportion of 0.23 and 0.34, respectively). Our study indicates that eschewing heavy metals and supplementing properly with trace essential elements are conducive to reducing the risk of PCOS.http://www.sciencedirect.com/science/article/pii/S0147651325008139Trace elementsQuantile-based g-computationMediation analyses
spellingShingle Xin Wang
Xueting Lai
Chenke Pan
Tao Yin
Wei Zhu
Xinyue Zhu
Jian Chen
Chunmei Liang
Dongmei Ji
The association between metal exposure in follicular fluid and PCOS risk in reproductive-aged women: Mediating Roles of LH/FSH ratio and androgens
Ecotoxicology and Environmental Safety
Trace elements
Quantile-based g-computation
Mediation analyses
title The association between metal exposure in follicular fluid and PCOS risk in reproductive-aged women: Mediating Roles of LH/FSH ratio and androgens
title_full The association between metal exposure in follicular fluid and PCOS risk in reproductive-aged women: Mediating Roles of LH/FSH ratio and androgens
title_fullStr The association between metal exposure in follicular fluid and PCOS risk in reproductive-aged women: Mediating Roles of LH/FSH ratio and androgens
title_full_unstemmed The association between metal exposure in follicular fluid and PCOS risk in reproductive-aged women: Mediating Roles of LH/FSH ratio and androgens
title_short The association between metal exposure in follicular fluid and PCOS risk in reproductive-aged women: Mediating Roles of LH/FSH ratio and androgens
title_sort association between metal exposure in follicular fluid and pcos risk in reproductive aged women mediating roles of lh fsh ratio and androgens
topic Trace elements
Quantile-based g-computation
Mediation analyses
url http://www.sciencedirect.com/science/article/pii/S0147651325008139
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