Bian Yating, Yue Yingxiao, Cheng Yufan, Wang Dan, He Lu, Yan Peixia, Song Huan, Wang Tong, Zhou Weidong, Zhang Xu, Pan Zhizhen, Liu Liangpo
Department of Public Health Laboratory Sciences, School of Public Health, Shanxi Medical University, Shanxi, China.
Changping Center for Disease Prevention and Control, Changping, Beijing, China.
Front Public Health. 2025 Jun 10;13:1526918. doi: 10.3389/fpubh.2025.1526918. eCollection 2025.
Per- and polyfluoroalkyl substances (PFAS) have been associated with polycystic ovarian syndrome (PCOS), however, the evidence is limited. This study aimed to explore the associations between PFAS in the follicular fluid and PCOS, as well as the mediating role of steroid hormones.
Forty women with PCOS undergoing treatment for infertility and 56 control participants were included in this study. The levels of 24 PFAS in the follicular fluid and sex hormones in serum were measured. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for each PFAS were estimated by multivariable logistic regression. Correlation analysis and multiple linear regression revealed the associations between PFAS and steroid hormones. Bayesian kernel machine regression (BKMR) model was utilized to evaluate the associations between joint and individual PFAS exposure and PCOS. Additionally, experiment with human ovarian granulosa cell line (KGN cells) was conducted.
The study showed that perfluoro-n-octanoic acid (PFOA) and potassium perfluoro-1-octanesulfonate (PFOS) were the dominant PFAS in the follicular fluid samples, with the median concentration of 4.35 ng/mL and 5.22 ng/mL, respectively. Perfluoro-n-hexanoic acid (PFHxA) were correlated with increased incidences of PCOS (medium vs. low tertile: OR = 1.78, 95% CI: 0.18, 17.19). In the cases, a negative relationship was found between PFHxA and luteinizing hormone (LH; β = -0.44, 95% CI: -8.25, -0.03), while a positive relationship was observed between perfluoro-n-heptanoic acid (PFHpA) and LH (β = 0.504, 95% CI: 0.71, 21.31). PFOA was positively associated with estradiol (E; β = 0.76, 95% CI: 1.52, 19.57). The BKMR model indicated that there might be a joint effect between PFAS mixtures and PCOS, with the posterior inclusion probabilities (PIP) of PFHxA was 0.983. In the cell experiments, PFOA, PFOS, and PFHpA exposure decreased the concentration of E ( < 0.05).
PFHxA in follicular fluids was associated with the elevated odds of PCOS, and steroid hormones may play a role in the etiologic connection.
全氟和多氟烷基物质（PFAS）已被认为与多囊卵巢综合征（PCOS）有关，然而，证据有限。本研究旨在探讨卵泡液中PFAS与PCOS之间的关联，以及类固醇激素的中介作用。
本研究纳入了40名接受不孕症治疗的PCOS女性和56名对照参与者。测量了卵泡液中24种PFAS的水平和血清中性激素的水平。通过多变量逻辑回归估计每种PFAS的调整优势比（OR）和95%置信区间（CI）。相关性分析和多元线性回归揭示了PFAS与类固醇激素之间的关联。利用贝叶斯核机器回归（BKMR）模型评估联合和个体PFAS暴露与PCOS之间的关联。此外，还进行了人卵巢颗粒细胞系（KGN细胞）实验。
研究表明，全氟辛酸（PFOA）和全氟辛烷磺酸钾（PFOS）是卵泡液样本中主要的PFAS，中位浓度分别为4.35 ng/mL和5.22 ng/mL。全氟己酸（PFHxA）与PCOS发病率增加相关（中三分位数与低三分位数相比：OR = 1.78，95% CI：0.18，17.19）。在病例中，发现PFHxA与促黄体生成素（LH；β = -0.44，95% CI：-8.25，-0.03）呈负相关，而全氟庚酸（PFHpA）与LH呈正相关（β = 0.504，95% CI：0.71，21.31）。PFOA与雌二醇（E；β = 0.76，95% CI：1.52，19.57）呈正相关。BKMR模型表明，PFAS混合物与PCOS之间可能存在联合效应，PFHxA的后验包含概率（PIP）为0.983。在细胞实验中，PFOA、PFOS和PFHpA暴露降低了E的浓度（<0.05）。
卵泡液中的PFHxA与PCOS的高发病几率相关，类固醇激素可能在病因联系中起作用。
