辅助生殖技术治疗女性孕前全氟和多氟烷基化合物暴露与其月经特征的关联

Impacts of pre-pregnancy exposure to per- and polyfluoroalkyl substances on menstrual characteristics among women undergoing assisted reproductive technology

  • 摘要:
    背景 全氟和多氟烷基化合物(PFAS)是一类持久性有机污染物,广泛应用于各种产品中,导致人群暴露和长期累积。目前我国有关辅助生殖技术(ART)治疗女性孕前PFAS暴露与月经特征关联的研究缺乏。
    目的 探索ART治疗女性孕前PFAS暴露与接受ART治疗前月经特征的关联。
    方法 本研究采用横断面研究设计,在2017—2020年期间,于上海交通大学医学院附属国际和平妇幼保健院的生殖门诊招募接受ART治疗的女性作为研究对象。采用超高效液相色谱-串联质谱法检测孕前血清样本中的42种PFAS。使用问卷调查ART治疗女性的人口学特征、生活习惯以及月经特征(平均月经周期时长、平均月经经期时长、月经不规律和月经出血量)等信息。采用多重线性回归、二元logistic回归和多分类logistic回归分析ART治疗女性孕前单一PFAS暴露与其月经特征的关系,采用加权分位数和(WQS)回归模型分析PFAS混合物与其月经特征的关系。
    结果 研究对象的孕前血清样本中共有15种PFAS检出率大于60%,包括全氟庚酸(PFHpA)、全氟辛酸(PFOA)、全氟壬酸(PFNA)、全氟癸酸(PFDA)、全氟十一酸(PFUnDA)、全氟十二酸(PFDoDA)、全氟丁烷磺酸(PFBS)、全氟己烷磺酸(PFHxS)、全氟庚烷磺酸(PFHpS)、全氟辛烷磺酸(PFOS)、6:2 氯代多氟醚基磺酸(6:2 Cl-PFESA)、8:2 氯代多氟醚基磺酸(8:2 Cl-PFESA)、全氟-2-丙氧基丙酸(HFPO-DA)、全氟-2-甲氧基乙酸(PFMOAA)、全氟-3,5,7,9,11-五氧杂十二烷酸(PFO5DoDA)。其中PFOA的中位质量浓度(后简称为浓度)最高,为9.160 ng·mL−1。单一PFAS暴露分析结果显示PFAS暴露与研究人群月经周期不规律的发生呈正相关,随着PFOA、PFBS、PFHxS每增加e个单位水平,月经周期不规律的发生风险分别增加57%、42%和39%。大多数PFAS与平均月经周期时长呈正相关,如PFHpA(b=1.08,95%CI:0.11~2.05)、PFOA(b=1.69,95%CI:0.39~3.00)、PFBS(b=1.23,95%CI:0.25~2.22)、PFHxS(b=1.47,95%CI:0.61~2.32)、PFHpS(b=1.48,95%CI:0.35~2.61)和6:2 Cl-PFESA(b=0.90,95%CI:0.08~1.72)。此外,PFHpA(OR=1.39,95%CI:1.06~1.82)、PFOA(OR=1.58,95%CI:1.09~2.30)、PFBS(OR=1.37,95%CI:1.04~1.80)、PFHxS(OR=1.34,95%CI:1.05~1.71)、PFHpS(OR=1.53,95%CI:1.10~2.14)和6:2 Cl-PFESA(OR=1.34,95%CI:1.06~1.70)暴露与月经量少的发生呈正相关;PFOA(OR=0.40,95%CI:0.23~0.71)、PFHpS(OR=0.45,95%CI:0.29~0.71)和HFPO-DA(OR=0.68,95%CI:0.48~0.97)与月经量多的发生呈负相关。混合暴露模型显示PFAS混合物与平均月经周期时长呈正相关(b=1.60,95%CI:0.49~2.71),与月经周期不规律的发生呈正相关(OR=1.77,95%CI:1.19~2.63),与月经出血量少的发生呈正相关(OR=1.59,95%CI:1.08~2.35),与月经出血量多的发生呈负相关(OR=0.40,95%CI:0.22~0.73)。
    结论 上海地区ART治疗女性孕前广泛暴露于PFAS。孕前PFAS暴露可能与ART治疗女性接受ART治疗前的月经特征有关,但仍需要更多的人群数据验证本研究结果。

     

    Abstract:
    Background Per- and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollutants widely used in various products, leading to population exposure and long-term accumulation. At present, there is a lack of research on the relationships between pre-pregnancy PFAS and menstrual characteristics among women undergoing assisted reproductive technology (ART) in China.
    Objective To explore the relationships between pre-pregnancy PFAS exposure among women undergoing ART and menstrual characteristics prior to assisted reproductive treatment.
    Methods This study employed a cross-sectional research design, recruiting women undergoing ART treatment at the Reproductive Clinic of the International Peace Maternity & Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, from 2017 to 2020 as study participants. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to detect 42 types of PFAS in pre-pregnancy serum samples. Questionnaires were administered to collect information on demographic characteristics, lifestyle habits, and menstrual characteristics (average menstrual cycle length, average menstrual period length, menstrual irregularities, and menstrual bleeding volume) of women undergoing ART. Multiple linear regression, binary logistic regression, and multinomial logistic regression analyses were performed to investigate the relationships between individual PFAS exposure before pregnancy and menstrual characteristics among ART women. Additionally, weighted quantile sum (WQS) model was applied to analyze the association between PFAS mixtures and menstrual characteristics.
    Results In the pre-pregnancy serum samples of the study population, 15 PFAS were detected in more than 60% of the samples, including perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), perfluorobutanesulfonic acid (PFBS), perfluorohexanesulfonic acid (PFHxS), perfluoroheptanesulfonic acid (PFHpS), perfluorooctanesulfonic acid (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 chlorinated polyfluorinated ether sulfonate (8:2 Cl-PFESA), perfluoro-2-propoxypropanoic acid (HFPO-DA), perfluoro-2-methoxyacetic acid (PFMOAA), and perfluoro-(3,5,7,9,11-pentaoxadodecanoic) acid (PFO5DoDA). Among them, PFOA had the highest median concentration of 9.160 ng·mL−1. The single PFAS exposure analysis revealed a positive correlation between PFAS and irregular menstrual cycles. Specifically, for every natural-log unit (e) increase in PFOA, PFBS, or PFHxS level, the incidence of irregular menstrual cycles increased by 57%, 42%, or 39%, respectively. Most PFAS were positively correlated with the average number of menstrual cycle days, such as PFHpA (b=1.08, 95%CI: 0.11, 2.05), PFOA (b=1.69, 95%CI: 0.39, 3.00), PFBS (b=1.23, 95%CI: 0.25, 2.22), PFHxS (b=1.47, 95%CI: 0.61, 2.32), PFHpS (b=1.48, 95%CI: 0.35, 2.61), and 6:2 Cl-PFESA (b=0.90, 95%CI: 0.08, 1.72). Furthermore, levels of PFHpA (OR=1.39, 95%CI: 1.06, 1.82), PFOA (OR=1.58, 95%CI: 1.09, 2.30), PFBS (OR=1.37, 95%CI: 1.04, 1.80), PFHxS (OR=1.34, 95%CI: 1.05, 1.71), PFHpS (OR=1.53, 95%CI: 1.10, 2.14), and 6:2 Cl-PFESA (OR=1.34, 95%CI: 1.06, 1.70) were positively correlated with low menstrual blood volume, while PFOA (OR=0.40, 95%CI: 0.23, 0.71), PFHpS (OR=0.45, 95%CI: 0.29, 0.71), and HFPO-DA (OR=0.68, 95%CI: 0.48, 0.97) were negatively correlated with high menstrual blood volume. The mixed exposure model showed that PFAS mixtures were positively correlated with the average number of menstrual cycle days (b=1.60, 95%CI: 0.49, 2.71), irregular menstrual cycles (OR=1.77, 95%CI: 1.19, 2.63), and low menstrual blood volume (OR=1.59, 95%CI: 1.08, 2.35), but negatively correlated with high menstrual blood volume (OR=0.40, 95%CI: 0.22, 0.73).
    Conclusion Women undergoing ART in Shanghai are widely exposed to PFAS prior to conception. Exposure to PFAS before pregnancy may be related to menstrual characteristics among women seeking ART before undergoing fertility treatments, but additional data from larger populations are required to validate the findings of this study.

     

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