传统与新型全氟化合物对育龄期女性生殖激素的影响

Association of novel and legacy PFAS with reproductive hormones in women of child-bearing age

目的:探讨传统与新型全氟化合物(per-and polyfluoroalkyl substances,PFAS)在育龄女性中的暴露水平及对育龄期女性生殖激素的影响。方法:采用横断面调查研究设计,于2013~2015年间对433名正常育龄期女性进行问卷调查,收集其年龄、月经初潮年龄、产次、BMI、教育水平和家庭收入情况等信息,同时采集血液样本检测生殖激素水平,利用超高效液相色谱-串联质谱法测定血浆中PFAS浓度。采用多元线性回归和Quantile g-computation模型来评估PFAS混合暴露与生殖激素的关联。结果:研究人群血浆中全氟和多氟烷醚类化合物:6∶2全氟聚醚磺酸(6∶2 Cl-PFESA)、8∶2全氟聚醚磺酸(8∶2 Cl-PFESA)和六氟环氧丙烷二聚酸(HFPO-DA)的检出率分别为100%,99.8%和99.9%。且全氟和多氟烷醚类化合物的浓度:6∶2 Cl-PFESA(2.27 ng/mL)、8∶2 Cl-PFESA(0.07 ng/mL)和HFPO-DA(0.03 ng/mL)处于较高水平。多元线性回归结果发现支链PFAS异构体与孕酮成正相关:1m-PFOS(β=0.131,95%CI:0.021,0.242),br-PFOS(β=0.119,95%CI:0.005,0.234),混合暴露模型中发现PFAS与孕酮呈正相关(β=0.549,95%CI:0.323,0.774)。结论:本研究采用混合暴露模型的分析方法评估PFAS混合物的联合作用,反应了多种环境PFAS暴露与生殖激素的关联,发现了育龄期妇女新型PFAS浓度处于较高水平,证实PFAS暴露可能与育龄期女性生殖激素紊乱有关。

Objective:To evaluate the legacy and novel per-and polyfluoroalkyl substances(PFAS)exposure in women of reproductive age,and to explore the effects on female reproductive hormones.Methods:We used cross-sectional data of 433 normal women of reproductive age from 2013 to 2015.Data of age,age at menarche,parity,BMI,education,and income were collected through questionnaires,serum samples were collected for reproductive hormones,and plasma samples for PFAS measurement by ultraperformance liquid chromatography-tandem mass spectrometer(UPLC-MS/MS).Multiple linear regression and quantile g-computation were adopted to analyze the association between PFAS and reproductive hormones.Results:The detection rates of 6:2 Cl-PFESA,8:2 Cl-PFESA and HFPO-DA in the plasma were 100%,99.8% and 99.9%,respectively.The median concentrations of these chemicals were 2.27 ng/mL,0.07 ng/mL and 0.03 ng/mL,respectively.Multiple linear regression analysis showed a positive association between branched PFOS[1m-PFOS(β=0.131,95%CI:0.021,0.242),br-PFOS(β=0.119,95%CI:0.005,0.234)]and progesterone.In addition,mixed exposure model suggested that PFAS had a positive association with progesterone(β=0.549,95%CI:0.323,0.774).Conclusion:In this study,a mixed exposure model was used to evaluate the combined effects of PFAS mixtures,reflecting the association between multiple environmental PFAS exposure and reproductive hormones,and a higher concentration of novel PFAS was found in women of reproductive age,confirming that PFAS exposure may be related to reproductive hormone disorders in women of reproductive age.