为探讨孕期有机氯农药(OCPs)暴露对新生儿性激素水平和出生体格的影响,以广州市271对母婴人群为研究对象,在新生儿出生后24h内采集胎粪样品,分析胎粪中10种OCPs和7种性激素含量.采用广义线性模型(GLM)分析OCPs与出生体格评分的关联,并采用中介效应模型评估性激素在OCPs暴露与出生体格评分关联的中介作用.结果显示,新生儿胎粪中主要的OCPs为2,2-双-(对氯苯基)-1,1-二氯乙烯(p,p'-DDE),其浓度范围为nd~0.25nmol/g (中值为0.05nmol/g).胎粪中孕酮(Progesterone,P4)、雄烯二酮(Androstenedione,AED)、睾酮(Testosterone,T)、雌酮(Estrone,E1)、雌二醇(Estradiol,E2)、雌三醇(Estriol,E3)等性激素的中值分别为1.80,0.24,0.13,0.15,0.38和8.24nmol/g.p,p'-DDE暴露水平每增加1nmol/g,胎粪中AED、T和E3分别增加1.82(95% CI:0.34,3.29)、1.31(95% CI:0.03,2.60)和8.68(95% CI:3.99,13.4) nmol/g.对于男性新生儿,p,p'-DDE浓度每增加1nmol/g,E3增加9.12(95% CI:3.11,14.9) nmol/g;女性新生儿Σ10OCPs暴露水平每增加1nmol/g,E2/T值减少11.8(95% CI:-22.8,-0.84) nmol/g.p,p'-DDE暴露可能通过调节E3对男性新生儿的身长评分(BLZ)产生影响,其间接效应为0.73,中介效应百分比为25.3%.Σ10OCPs暴露则可能通过调节E2/T对女性新生儿的头围评分(HCZ)产生影响,间接效应为-0.18,中介效应百分比为19.4%.孕期OCPs暴露可能通过调节新生儿性激素水平影响其出生体格评分变化.
Abstract
To investigate the impact of organochlorine pesticides (OCPs) exposure during pregnancy on neonatal sex hormone levels and birth physique, this study recruited 271 mother-infant pairs from Guangzhou and collected meconium samples within 24hours postpartum. The levels of ten OCPs and seven sex hormones in meconium were analyzed. The generalized linear model (GLM) was employed to explore the association between OCP exposure and birth physique scores. Additionally, the mediation effect model was utilized to assess the mediating role of sex hormones in the relationship between OCP exposure and birth physique scores. The results indicated that the predominant OCPs in neonatal meconium was p,p'-DDE, with concentration range of not detected (nd) to 0.25nmol/g (median 0.05nmol/g). The median levels of progesterone (P4), androstenedione (AED), testosterone (T), estrone (E1), estradiol (E2), and estriol (E3) in meconium were 1.80, 0.24, 0.13, 0.15, 0.38, and 8.24nmol/g respectively. For each unit increase in p,p'-DDE exposure level, AED, T, and E3 in meconium increased by 1.82 (95% CI: 0.34, 3.29), 1.31 (95% CI: 0.03, 2.60), and 211 (95% CI: 120, 302), respectively. In male newborns, for each unit increase in p,p'-DDE concentration was associated with an increase of 9.12 (95% CI: 3.11, 14.9) in E3leevels. Conversely, in female newborns, for each unit increase in Σ10OCPs concentration resulted in a decrease of 11.8 (95% CI: - 22.8, - 0.84) in the E2/T ratio. Exposure to p,p' - DDE may influence the birth length-Zscore (BLZ) in male neonates through the regulation of E3, with an indirect effect of 0.73 and a mediation effect percentage of 25.3%. Exposure to Σ10OCPs may impact head circumference-Zscore (HCZ) in female neonates via regulating E2/T ratio, with an indirect effect of - 0.18 and a mediation effect percentage of 19.4%. Exposure to OCPs during pregnancy may affect the changes in birth physique scores of neonates by regulating their sex hormone levels.
关键词
出生体格 /
胎粪 /
性激素 /
有机氯农药 /
孕期暴露
Key words
birth physical /
meconium /
organochlorine pesticides /
prenatal exposure /
sex hormones
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Li C, Cheng Y, Tang Q, et al. The association between prenatal exposure to organochlorine pesticides and thyroid hormone levels in newborns in Yancheng, China[J]. Environmental Research, 2014,129:47-51.
[2] Zhang G, Parker A, House A, et al. Sedimentary records of DDT and HCH in the Pearl River Delta, South China[J]. Environmental Science& Technology, 2002,36(17):3671-3677.
[3] Dewan P, Jain V, Gupta P, et al. Organochlorine pesticide residues in maternal blood, cord blood, placenta, and breastmilk and their relation to birth size[J]. Chemosphere, 2013,90(5):1704-1710.
[4] Li Q F, Lu Y L, Wang P, et al. Distribution, source, and risk of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in urban and rural soils around the Yellow and Bohai Seas, China[J]. Environmental Pollution, 2018,239:233-241.
[5] Yin S J, Sun Y, Yu J H, et al. Prenatal exposure to organochlorine pesticides is associated with increased risk for neural tube defects[J]. Science of the Total Environment, 2021,770:145284.
[6] Hellar-Kihampa H, De Wael K, Lugwisha E, et al. Spatial monitoring of organohalogen compounds in surface water and sediments of a rural-urban river basin in Tanzania[J]. Science of the Total Environment, 2013,447:186-197.
[7] Peng F J, Hardy E M, Mezzache S, et al. Exposure to multiclass pesticides among female adult population in two Chinese cities revealed by hair analysis[J]. Environment International, 2020,138:105633.
[8] Koureas M, Rousou X, Haftiki H, et al. Spatial and temporal distribution of p,p¢-DDE (1dichloro 2,2bis (p chlorophenyl) ethylene) blood levels across the globe. A systematicreview and meta-analysis[J]. Science of the Total Environment, 2019,686:440-451.
[9] Hu L Q, Luo D, Wang L M, et al. Levels and profiles of persistent organic pollutants in breast milk in China and their potential health risks to breastfed infants:A review[J]. Science of the Total Environment, 2021,753:142028.
[10] Cao X, Tan Q, Wang M, et al. Cross-sectional and longitudinal associations of dichlorodiphenyltrichloroethane (DDT) metabolites exposure with lung function alternation in the Chinese general adults[J]. Science of The Total Environment, 2023,905:167229.
[11] Lee H, Ko E, Shin S, et al. Differential mitochondrial dysregulation by exposure to individual organochlorine pesticides (OCPs) and their mixture in zebrafish embryos[J]. Environmental Pollution, 2021,277:115904.
[12] Anand M, Taneja A. Organochlorine pesticides residue in placenta and their influence on anthropometric measures of infants[J]. Environmental Research, 2020,182:109106.
[13] Qi S Y, Xu X L, Ma W Z, et al. Effects of organochlorine pesticide residues in maternal body on infants[J]. Frontiers in Endocrinology, 2022,13:890307.
[14] Gueil-Oumrait N, Stratakis N, Maitre L, et al. Prenatal exposure to chemical mixtures and metabolic syndrome risk in children[J]. JAMA Network Open, 2024,7(5):12040.
[15] Alvarez-Silvares E, Rubio-Cid P, González-Gómez X, et al. Determination of organic pollutants in meconium and its relationship with fetal growth. Case control study in Northwestern Spain[J]. Journal of Perinatal Medicine, 2021,49(7):884-896.
[16] Al-Saleh I, Al-Doush I, Alsabbaheen A, et al. Levels of DDT and its metabolites in placenta, maternal and cord blood and their potential influence on neonatal anthropometric measures[J]. Science of the Total Environment, 2012,416:62-74.
[17] Ruis M, Hoffman K, Stapleton H M. Brominated flame retardants and legacy organochlorines in archived human placenta samples:Sex differences, temporal analysis and associations with infant birth weight[J]. Chemosphere, 2023,322:138170.
[18] Ouidir M, Louis G B M, Kanner J, et al. Association of maternal exposure to persistent organic pollutants in early pregnancy with fetal growth[J]. JAMA Pediatrics, 2020,174(2):149-161.
[19] Yang C H, Fang J, Sun X J, et al. Prenatal exposure to organochlorine pesticides and infant growth:A longitudinal study[J]. Environment International, 2021,148:106374.
[20] Yalçin S S, Gunes B, Arikan K, et al. Exploring the levels of persistent organic pollutants in umbilical cord blood and their connection to gestational age and birth weights inŞanlıurfa, Turkey[J]. BMC Pregnancy and Childbirth, 2024,24(1):2-16.
[21] Yamazaki K, Itoh S, Araki A, et al. Associations between prenatal exposure to organochlorine pesticides and thyroid hormone levels in mothers and infants:The Hokkaido study on environment and children's health[J]. Environmental Research, 2020,189:109840.
[22] Araki A, Miyashita C, Mitsui T, et al. Prenatal organochlorine pesticide exposure and the disruption of steroids and reproductive hormones in cord blood:The Hokkaido study[J]. Environment International, 2018,110:1-13.
[23] Parisi F A O, Fenizia C A O, Introini A A O, et al. The pathophysiological role of estrogens in the initial stages of pregnancy:molecular mechanisms and clinical implications for pregnancy outcome from the periconceptional period to end of the first trimester[J]. Human Reproduction Update, 29(6):699-720.
[24] Kolatorova L A O, Vitku J A O, Suchopar J, et al. Progesterone:A steroid with wide range of effects in physiology as well as human medicine.[J]. International Journal of Molecular Sciences, 2022, 23(14):7989.
[25] Morel Y, Roucher F, Plotton I, et al. Evolution of steroids during pregnancy:Maternal, placental and fetal synthesis[J]. Annales d'Endocrinologie, 2016,77(2):82-89.
[26] Wang L, Qie Y, Yang Y, et al. Binding and activation of estrogen-related receptor γ:A novel molecular mechanism for the estrogenic disruption effects of DDT and its metabolites[J]. Environmental Science& Technology, 2022,56(17):12358-12367.
[27] Yilmaz B, Terekeci H, Sandal S, et al. Endocrine disrupting chemicals:exposure, effects on human health, mechanism of action, models for testing and strategies for prevention[J]. Reviews in Endocrine& Metabolic Disorders, 2020,21(1):127-147.
[28] van den Berg H, Manuweera G, Konradsen F. Global trends in the production and use of DDT for control of malaria and other vector-borne diseases[J]. Malaria Journal, 2017,16:401.
[29] Mehta R V, Sreenivasa M A, Mathew M, et al. A mixed-methods study of pesticide exposures in Breastmilk and Community& Lactating Women's perspectives from Haryana, India[J]. BMC Public Health, 2020,20(1):3-14.
[30] Kou J, Li X, Zhang M Y, et al. Accumulative levels, temporal and spatial distribution of common chemical pollutants in the blood of Chinese adults[J]. Environmental Pollution, 2022,311:119980.
[31] He C T, Yan X, Wang M H, et al. Dichloro-diphenyl-trichloroethanes (DDTs) in human hair and serum in rural and urban areas in South China[J]. Environmental Research, 2017,155:279-286.
[32] Cai F S, Tang B, Zheng J, et al. Fetal exposure to organic contaminants revealed by infant hair:A preliminary study in south China[J]. Environmental Pollution, 2023,316:120536.
[33] Fernández-Cruz T,Álvarez-Silvares E, Domínguez-Vigo P, et al. Prenatal exposure to organic pollutants in northwestern Spain using non-invasive matrices (placenta and meconium)[J]. Science of the Total Environment, 2020,731:138741.
[34] Jeong Y, Lee S, Kim S, et al. Occurrence and prenatal exposure to persistent organic pollutants using meconium in Korea:Feasibility of meconium as a non-invasive human matrix[J]. Environmental Research, 2016,147:8-15.
[35] Ostrea E M, Bielawski D M, Posecion N C, et al. Combined analysis of prenatal (maternal hair and blood) and neonatal (infant hair, cord blood and meconium) matrices to detect fetal exposure to environmental pesticides[J]. Environmental Research, 2009,109(1):116-122.
[36] 孙瑜,宋莉,马万里,等.石化工人多环芳烃暴露促进高血压中介机制分析[J].哈尔滨工业大学学报, 2024. Yu S, Li S, Wanli M, et al. Mediation analysis of hypertension induced by polycyclic aromatic hydrocarbon exposure in petrochemical workers[J]. Journal of Harbin Institute of Technology, 2024.
[37] 杨晨辉.宫内有机氯农药暴露与胎儿及0至2岁儿童生长发育的关联研究[D].武汉:华中科技大学, 2022. Yang C H. Associations of in utero organochlorine pesticides exposure with fetal growth and child growth in the first 2 years[D]. Wuhan:Huazhong University of Science and Technology, 2022.
[38] Lu G H, Shao P W, Zheng Y, et al. Perfluoroalkyl Substances (PFASs) in rivers and drinking waters from Qingdao, China[J]. International Journal of Environmental Research and Public Health, 2022,19(9):5722.
[39] Yang Z, Zhang S, Wang F, et al. Occurrence and health risk assessment of organic amine pesticides in drinking water of the Yangtze River delta urban agglomeration[J]. Journal of Environmental Sciences, 2025,152:99-110.
[40] Chen Y, Wang X, Li Y, et al. Persistent organic pollutants in matched breast milk and infant faeces samples[J]. Chemosphere, 2015,118:309-314.
[41] Zhao G, Xu Y, Li W, et al. Prenatal exposures to persistent organic pollutants as measured in cord blood and meconium from three localities of Zhejiang, China[J]. Science of the Total Environment, 2007,377(2):179-191.
[42] Araki A, Miyashita C, Mitsui T, et al. Prenatal organochlorine pesticide exposure and the disruption of steroids and reproductive hormones in cord blood:The Hokkaido study[J]. Environment International, 2018,110:1-13.
[43] Liao Q, Huang H, Tang P, et al. Associations of prenatal exposure to per-and polyfluoroalkyl substances and fetal sex hormones in the Guangxi Zhuang Birth Cohort Study:Greater effect of long-chain PFAS[J]. Ecotoxicology and Environmental Safety, 2024,272:116054.
[44] Martyniuk C J, Mehinto A C, Denslow N D. Organochlorine pesticides:Agrochemicals with potent endocrine-disrupting properties in fish[J]. Molecular and Cellular Endocrinology, 2020,507:110764.
[45] Kalinina T S, Kononchuk V V, Gulyaeva L F. Expressionofestrogen-, progesterone-, andandrogen-responsive genes in MCF-7 and MDA-MB-231cells treated with o,p¢-DDT, p,p¢-DDT, or endosulfan[J]. Journal of Biochemical and Molecular Toxicology, 2021,35(6):1-8.
[46] Kumar V, Yadav C S, Banerjee B D. Xeno-estrogenic pesticides and the risk of related human cancers[J]. Journal of Xenobiotics, 2022,12(4):344-355.
[47] Mnif W, Hassine A I H, Bouaziz A, et al. Effect of endocrine disruptor pesticides:A review[J]. International Journal of Environmental Research and Public Health, 2011,8(6):2265-2303.
[48] Yaglova N V, Tsomartova D A, Obernikhin S S, et al. Differential disrupting effects of prolonged low-dose exposure to dichlorodiphenyltrichloroethane on androgen and estrogen production in males[J]. International Journal of Molecular Sciences, 2021,22(6).
[49] Bornman M, Delport R, Farías P, et al. Alterations in male reproductive hormones in relation to environmental DDT exposure[J]. Environment International, 2018,113:281-289.
[50] Strand D, Nylander E, Hoeglund A, et al. Screening persistent organic pollutants for effects on testosterone and estrogen synthesis at human-relevant concentrations using H295R cells in 96-well plates[J]. Cell Biology and Toxicology, 2024,40(1):2-16.
[51] Warembourg C, Debost-Legrand A, Bonvallot N, et al. Exposure of pregnant women to persistent organic pollutants and cord sex hormone levels[J]. Human Reproduction, 2016,31(1):190-198.
[52] Vested A, Ramlau-Hansen C H, Olsen S F, et al. In utero exposure to persistent organochlorine pollutants and reproductive health in the human male[J]. Reproduction, 2014,148(6):635-646.
[53] Dukic J, Ehlert U J E. Longitudinal course of sex steroids from pregnancy to postpartum[J]. 2023,164(8):1-25.
[54] Pacyga D C, Papandonatos G D, Rosas L, et al. Associations of per-and polyfluoroalkyl substances with maternal early second trimester sex-steroid hormones[J]. International Journal of Hygiene and Environmental Health, 2024,259:114380.
[55] Wei L F, Yang Y Y, Li Q X, et al. Composition, distribution, and risk assessment of organochlorine pesticides in drinking water sources in South China[J]. Water Quality, Exposure and Health, 2015,7(1):89-97.
[56] Zhang F, Cui K P, Yuan X R, et al. Differentiated cognition of the effects of human activities on typical persistent organic pollutants and bacterioplankton community in drinking water source[J]. Environmental Research, 2024,252:118815.
[57] Bao L J, Maruya K A, Snyder S A, et al. China's water pollution by persistent organic pollutants[J]. Environmental Pollution, 2012,163:100-108.
基金
环境污染与疾病监控教育部重点实验室开放项目(GMU-2024-HJZ-05);中央级公益性科研院所基本科研业务专项(PM-zx703-202406-177)
PDF(866 KB)
京公网安备 11010802030352号 
