Environmental Exposure To Perfluoroalkyl Substances And Female Reproductive Health

Background: Perfluoroalkyl Substances(PFASs)are persistent organic chemicals that are widely used in industrial and commercial applications.It was considered as a potential endocrine disruptor both in vitro and in vivo studies.However,evidence from human studies is still scare and inconsistent.Objectives: To explore the association between PFASs and femal reproductive health.Methods: The analysis was performed in three populations.Ten PFAS concentrations were measured from plasma samples using high-performance liquid chromatography/tandem mass spectrometry(HPLC/MS-MS).1.Shanghai Birth Cohort.We enrolled 1182 women who came for the care at two preconception care clinics in Shanghai.Information on dietary and environmental factors was collected by questionnaires.First,we evaluated PFASs exposure levels in Shanghai residents and possible exposure routes of PFASs.Second,we analyzed the associations between PFASs exposure and fecundity and menstruation.2.Infertile women recruited from Women’s hospital school of medicine,Zhejiang University.Sex hormone and thyroid hormone levels were abstracted from medical record.The main infertile reasons of 500 women we recruited were oviduct obstruction and partner diagnosed with azoospermia.Associations between PFASs and sex hormones and thyroid hormones were analyzed in this population.3.Shanghai Obesity and Allergy Cohort.We recruited pregnant women in third trimester and collected cord blood at delivery.GDM and PIH diagnosis and birthweight were obtained through medical record.We measured a total of 687 cord blood PFASs concentrations.Associations between PFASs and pregnancycomplications and birth outcomes were analyzed in this cohort.Results:1.Perfluorooctanate(PFOA)was the most predominant PFAS(Median value:13.84ng/m L),followed by perfluorooctane sulfonate(PFOS)(10.49ng/m L).In the analysis of association between diet and PFASs,we found high correlation between consumption of animal liver and sea food and multiple PFASs.2.Menstruation and fecundity: PFOA,PFOS,PFNA and PFHx S exposure were positively associated with irregular cycle,long cycle,and negatively associated with menorrhagia.the strongest association was shown with PFHx S [irregular cycle OR 1.80(95%CI 1.17,2.77);long cycle 1.73(1.13,2.65);menorrhagia 0.14(0.06,0.36)].PFUA and PFHp A exposure may decrease the pregnancy rate.In COX regression models,PFASs concentrations were stratified into three levels.Lowest level as reference,PFUA: medium level HR 0.79(0.63,0.999),high level 0.93(0.75,1.17);PFHp A: medium level 0.76(0.61,0.95);high level 0.77(0.62,0.97).3.thyroid hormones and sex hormones: PFBS exposure was positively associated with t SH level,and negatively associated with FT4,TT4 and TT3 levels [TSH:β 0.61(95%CI 0.15,1.07);FT4:-0.15(-0.24,-0.05);TT4:-0.22(-0.37,-0.08);TT3:-0.13(-0.26,-0.01)].PFBS was negatively associated with testosterone [β-0.85(95%CI-1.68,-0.02)].After stratifying PFASs concentrations into two levels,we found positive associations between PFDA and PFUA exposure with LH level.Lower level as reference,[PFDA: β 0.15(95%CI 0.04,0.27);PFUA 0.18(0.06,0.29)].4.Pregnancy complications.PFOS,PFNA and PFDA exposure were positively associated with GDM.After adjusting for maternal age,prepregnancy BMI,maternal education level,parity and gestational week at delivery,a log-unit increase in PFNA was associated with a 2.1-fold increase odds in GDM(OR 2.13,95%CI: 1.11,4.10).PFBS exposure were positively associated with PIH.After adjusting for potential confounders,a log-unit increase in PFBS was associatedwith a 2.6-fold increase odds in PIH(OR 2.59,95%CI:1.28,5.23).5.Birthweight: PFDA、PFUA、PFHx S exposure were positively associated with PIH.the strongest association was shown with PFHx S.PFHx S concentrations were stratified into four levels(Q1-Q4).Q1 as reference,Q2 β-10.54(95%CI:-95.59,74.51);Q3-133.67(-219.59,-47.76);Q4-39.67(-126.53,47.19).Conclusions: Exposure to some PFASs may interfere with endocrine hormones,menstruation and decrease female fecundity;may also be associated with pregnancy comlications(GDM,PIH)and fetal growth.Further prospective studies are needed to verify our finding.