Article(id=1241408718802317576, tenantId=1146029695717560320, journalId=1234093305789726721, issueId=1241408710791189399, articleNumber=null, orderNo=null, doi=null, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1728835200000, receivedDateStr=2024-10-14, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773904502820, onlineDateStr=2026-03-19, pubDate=1745078400000, pubDateStr=2025-04-20, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773904502820, onlineIssueDateStr=2026-03-19, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773904502820, creator=13701087609, updateTime=1773904502820, updator=13701087609, issue=Issue{id=1241408710791189399, tenantId=1146029695717560320, journalId=1234093305789726721, year='2025', volume='45', issue='4', pageStart='1777', pageEnd='2368', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773904500911, creator=13701087609, updateTime=1773904624658, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241409229878259747, tenantId=1146029695717560320, journalId=1234093305789726721, issueId=1241408710791189399, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241409229878259748, tenantId=1146029695717560320, journalId=1234093305789726721, issueId=1241408710791189399, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=2264, endPage=2275, ext={EN=ArticleExt(id=1241408719867670857, articleId=1241408718802317576, tenantId=1146029695717560320, journalId=1234093305789726721, language=EN, title=A preliminary study on the exposure of organochlorine pesticides in neonates and their association with hormone levels in Guangzhou, columnId=1234106388687934088, journalTitle=China Environmental Science, columnName=Environmental Toxicology and Environmental Health, runingTitle=null, highlight=null, articleAbstract=

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.

, correspAuthors=Jing ZHENG, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=Ting HE, Feng-shan CAI, Bin TANG, Xiao YAN, Qi-long LIAO, Rui-xing QIN, Lu MA, Chun XIE, Jing ZHENG), CN=ArticleExt(id=1241408723252474447, articleId=1241408718802317576, tenantId=1146029695717560320, journalId=1234093305789726721, language=CN, title=广州市新生儿有机氯农药暴露特征及与激素水平的关联性初探, columnId=1234106394006311784, journalTitle=中国环境科学, columnName=环境毒理与健康, runingTitle=null, highlight=null, articleAbstract=

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.

, correspAuthors=郑晶, authorNote=null, correspAuthorsNote=
* 责任作者,研究员,
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何婷(2000-),女,贵州毕节人,贵州医科大学硕士研究生,研究方向为环境与健康..

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何婷(2000-),女,贵州毕节人,贵州医科大学硕士研究生,研究方向为环境与健康..

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何婷(2000-),女,贵州毕节人,贵州医科大学硕士研究生,研究方向为环境与健康..

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BLZ:身长评分,BWZ:体重评分,HCZ:头围评分. (a)和(b)分别代表p,p'-DDE和Σ10OCPs与出生体格评分的关联; *P<0.05

, figureFileSmall=C/RPLlsGdo0OQr/DiH8VJQ==, figureFileBig=vaoycincqWGTolCYH6QWxg==, tableContent=null), ArticleFig(id=1241408732010181153, tenantId=1146029695717560320, journalId=1234093305789726721, articleId=1241408718802317576, language=EN, label=Fig.3, caption=Results of Generalized Linear Model (GLM) for sex hormones in meconium and neonatal physical examination scores at birth (n=271), figureFileSmall=jCXW8HiaKVPGnL50TMss0A==, figureFileBig=+b81NUBJ6QTr/nyiJFpBhA==, tableContent=null), ArticleFig(id=1241408732261839416, tenantId=1146029695717560320, journalId=1234093305789726721, articleId=1241408718802317576, language=CN, label=图3, caption=胎粪中性激素与新生儿出生体格评分的广义线性回归模型结果(n=271)

(a)、(b)和(c)分别代表性激素与BLZ、BWZ和HCZ的关联.*P<0.05

, figureFileSmall=jCXW8HiaKVPGnL50TMss0A==, figureFileBig=+b81NUBJ6QTr/nyiJFpBhA==, tableContent=null), ArticleFig(id=1241408732421222988, tenantId=1146029695717560320, journalId=1234093305789726721, articleId=1241408718802317576, language=EN, label=Fig.4, caption=The mediating effect of sex hormones in meconium on the association between OCPs exposure and neonatal physical condition scores, figureFileSmall=6Gr5xbQywne1V521910GEQ==, figureFileBig=3IxEz0zXiw5ysfXw/hKwVQ==, tableContent=null), ArticleFig(id=1241408732559635035, tenantId=1146029695717560320, journalId=1234093305789726721, articleId=1241408718802317576, language=CN, label=图4, caption=胎粪性激素在OCPs暴露与新生儿体格评分关联中的中介效应

(a)男性新生儿BLZ,(b)女性新生儿HCZ

, figureFileSmall=6Gr5xbQywne1V521910GEQ==, figureFileBig=3IxEz0zXiw5ysfXw/hKwVQ==, tableContent=null), ArticleFig(id=1241408732668686957, tenantId=1146029695717560320, journalId=1234093305789726721, articleId=1241408718802317576, language=EN, label=Table 1, caption=

Information of target compounds and internal standard standards

, figureFileSmall=null, figureFileBig=null, tableContent=
中文名称英文名称缩写CAS分子式分子量
有机氯农药α-六六六α-Hexachlorocyclohexaneα-HCH319-84-6C6H6Cl6291
γ-六六六γ-Hexachlorocyclohexaneγ-HCH58-89-9C6H6Cl6291
β-六六六β-Hexachlorocyclohexaneβ-HCH319-85-7C6H6Cl6291
δ-六六六δ-Hexachlorocyclohexaneδ-HCH319-86-8C6H6Cl6291
o,p'-滴滴伊2,4'-Dichlorodiphenyldichloroethyleneo,p'-DDE3424-82-6C14H8Cl4318
o,p'-滴滴滴2,4'-Dichlorodiphenyldichloroethaneo,p'-DDD53-19-0C14H10Cl4320
o,p'-滴滴涕2,4'-Dichlorodiphenyltrichloroethaneo,p'-DDT789-02-6C14H9Cl5355
p,p'-滴滴伊4,4'-Dichlorodiphenyldichloroethylenep,p'-DDE72-55-9C14H8Cl4318
p,p'-滴滴滴4,4'-Dichlorodiphenyldichloroethanep,p'-DDD72-54-8C14H10Cl4320
p,p'-滴滴涕4,4'-Dichlorodiphenyltrichloroethanep,p'-DDT50-29-3C14H9Cl5355
内标化合物
六溴二苯醚2,2',3,3',4,4'-hexabromodiphenyl etherBDE128182677-28-7C12H4Br6O644
性激素孕酮progesteroneP457-83-0C21H30O2315
羟基孕酮17-OH progesterone17-OHP68-79-1C21H30O3331
雄烯二酮AndrostenedioneAED63-05-8C19H26O2286
睾酮TestosteroneT58-22-0C19H28O2288
雌酮EstroneE153-16-7C18H22O2270
雌二醇EstradiolE250-28-2C18H24O2272
雌三醇EstriolE350-27-1C18H24O3288
内标化合物雌酮-d2Estrone-d2E1-d256588-58-0C18H22O2272
雌二醇-d4Estradiol-d4E2-d466789-03-5C18H24O2276
雌三醇-d2Estriol-d2E3-d253866-32-3C18H24O3290
孕酮-d9Progesterone-d9P4-d915775-74-3C21H30O2324
睾酮-d3Testosterone-d3T-d377546-39-5C19H28O2291
), ArticleFig(id=1241408732790321790, tenantId=1146029695717560320, journalId=1234093305789726721, articleId=1241408718802317576, language=CN, label=表1, caption=

目标化合物及内标标准品信息

, figureFileSmall=null, figureFileBig=null, tableContent=
中文名称英文名称缩写CAS分子式分子量
有机氯农药α-六六六α-Hexachlorocyclohexaneα-HCH319-84-6C6H6Cl6291
γ-六六六γ-Hexachlorocyclohexaneγ-HCH58-89-9C6H6Cl6291
β-六六六β-Hexachlorocyclohexaneβ-HCH319-85-7C6H6Cl6291
δ-六六六δ-Hexachlorocyclohexaneδ-HCH319-86-8C6H6Cl6291
o,p'-滴滴伊2,4'-Dichlorodiphenyldichloroethyleneo,p'-DDE3424-82-6C14H8Cl4318
o,p'-滴滴滴2,4'-Dichlorodiphenyldichloroethaneo,p'-DDD53-19-0C14H10Cl4320
o,p'-滴滴涕2,4'-Dichlorodiphenyltrichloroethaneo,p'-DDT789-02-6C14H9Cl5355
p,p'-滴滴伊4,4'-Dichlorodiphenyldichloroethylenep,p'-DDE72-55-9C14H8Cl4318
p,p'-滴滴滴4,4'-Dichlorodiphenyldichloroethanep,p'-DDD72-54-8C14H10Cl4320
p,p'-滴滴涕4,4'-Dichlorodiphenyltrichloroethanep,p'-DDT50-29-3C14H9Cl5355
内标化合物
六溴二苯醚2,2',3,3',4,4'-hexabromodiphenyl etherBDE128182677-28-7C12H4Br6O644
性激素孕酮progesteroneP457-83-0C21H30O2315
羟基孕酮17-OH progesterone17-OHP68-79-1C21H30O3331
雄烯二酮AndrostenedioneAED63-05-8C19H26O2286
睾酮TestosteroneT58-22-0C19H28O2288
雌酮EstroneE153-16-7C18H22O2270
雌二醇EstradiolE250-28-2C18H24O2272
雌三醇EstriolE350-27-1C18H24O3288
内标化合物雌酮-d2Estrone-d2E1-d256588-58-0C18H22O2272
雌二醇-d4Estradiol-d4E2-d466789-03-5C18H24O2276
雌三醇-d2Estriol-d2E3-d253866-32-3C18H24O3290
孕酮-d9Progesterone-d9P4-d915775-74-3C21H30O2324
睾酮-d3Testosterone-d3T-d377546-39-5C19H28O2291
), ArticleFig(id=1241408732899373706, tenantId=1146029695717560320, journalId=1234093305789726721, articleId=1241408718802317576, language=EN, label=Table 2, caption=

Mass spectrometric information of target compounds and internal standards

, figureFileSmall=null, figureFileBig=null, tableContent=
化合物初级离子(m/z)次级离子(m/z)保留时间(min)碰撞能(eV)检测仪器
有机氯农药a-HCH2171817.59GC-MS/MS
b-HCH2171818.45
g-HCH2171818.72
y-HCH2171819.77
o,p'-DDD23516512.6
o,p'-DDE24617612.7
p,p'-DDD23516513.1
p,p'-DDE24617613.2
p,p'-DDT23516513.3
o,p'-DDT23516513.3
内标化合物BDE12840432516.5
性激素P4315109/975.2830/27LC-MS/MS
17-OHP331109/974.8630/28
T289109/974.8732/26
AED287109/974.9730/27
E1269145/1434.76-47/-71
E2271145/1834.70-47/-49
E3287171/1454.19-45/-50
内标化合物E1-d2271145/1594.71-47/-71
E2-d4275147/1874.68-47/-49
E3-d2289173/1474.17-45/-50
P4-d93253065.2219
T-d329296.9/1094.8632/26
), ArticleFig(id=1241408733058757278, tenantId=1146029695717560320, journalId=1234093305789726721, articleId=1241408718802317576, language=CN, label=表2, caption=

目标化合物及内标的质谱信息

, figureFileSmall=null, figureFileBig=null, tableContent=
化合物初级离子(m/z)次级离子(m/z)保留时间(min)碰撞能(eV)检测仪器
有机氯农药a-HCH2171817.59GC-MS/MS
b-HCH2171818.45
g-HCH2171818.72
y-HCH2171819.77
o,p'-DDD23516512.6
o,p'-DDE24617612.7
p,p'-DDD23516513.1
p,p'-DDE24617613.2
p,p'-DDT23516513.3
o,p'-DDT23516513.3
内标化合物BDE12840432516.5
性激素P4315109/975.2830/27LC-MS/MS
17-OHP331109/974.8630/28
T289109/974.8732/26
AED287109/974.9730/27
E1269145/1434.76-47/-71
E2271145/1834.70-47/-49
E3287171/1454.19-45/-50
内标化合物E1-d2271145/1594.71-47/-71
E2-d4275147/1874.68-47/-49
E3-d2289173/1474.17-45/-50
P4-d93253065.2219
T-d329296.9/1094.8632/26
), ArticleFig(id=1241408733239112366, tenantId=1146029695717560320, journalId=1234093305789726721, articleId=1241408718802317576, language=EN, label=Table 3, caption=

The spiked recovery rate of target compounds in matrix samples

, figureFileSmall=null, figureFileBig=null, tableContent=
化合物简称基质加标定量限(nmol/g)
回收率(%)相对标准差(%)
有机氯农药a-HCH72.38.870.01
b-HCH76.614.70.05
g-HCH72.76.620.02
y-HCH64.61.330.09
o,p'-DDD1208.830.01
o,p'-DDE10315.20.01
p,p'-DDD99.611.90.01
p,p'-DDE1022.720.01
p,p'-DDT97.812.70.01
o,p'-DDT72.86.550.11
性激素P41041.460.26
17-OHP95.61.460.15
AED11515.90.21
T1095.550.06
E11048.210.07
E211214.30.01
E397.42.490.02
), ArticleFig(id=1241408733411078846, tenantId=1146029695717560320, journalId=1234093305789726721, articleId=1241408718802317576, language=CN, label=表3, caption=

基质样品目标化合物的加标回收率

, figureFileSmall=null, figureFileBig=null, tableContent=
化合物简称基质加标定量限(nmol/g)
回收率(%)相对标准差(%)
有机氯农药a-HCH72.38.870.01
b-HCH76.614.70.05
g-HCH72.76.620.02
y-HCH64.61.330.09
o,p'-DDD1208.830.01
o,p'-DDE10315.20.01
p,p'-DDD99.611.90.01
p,p'-DDE1022.720.01
p,p'-DDT97.812.70.01
o,p'-DDT72.86.550.11
性激素P41041.460.26
17-OHP95.61.460.15
AED11515.90.21
T1095.550.06
E11048.210.07
E211214.30.01
E397.42.490.02
), ArticleFig(id=1241408733578851022, tenantId=1146029695717560320, journalId=1234093305789726721, articleId=1241408718802317576, language=EN, label=Table 4, caption=

Maternal and infant demographic characteristics and distribution of grouped OCPs (n=271)

, figureFileSmall=null, figureFileBig=null, tableContent=
母婴人口学特征胎粪中主要OCPs按人口学特征分组浓度(nmol/g)
特征指标均值±标准差频率(%)p,p'-DDE中值(P25P75)PΣ10OCPs中值(P25P75)P
年龄≤ 2530 ± 4.5028 (10.3)0.04 (0.02,0.11)0.400.07 (0.03,0.4)0.14
26 ~ 34197 (72.7)0.04 (0.03,0.08)0.07 (0.03,0.2)
≥ 3546 (17)0.05(0.03,0.11)0.10 (0.03,0.37)
孕前BMI(kg/m2)< 18.521 ± 2.9043 (15.9)0.04(0.03,0.06)0.310.05(0.03,0.21)0.67
18.5 ~ 23.9178 (65.7)0.04 (0.03,0.09)0.07 (0.03,0.18)
≥ 2434 (12.6)0.05 (0.03,0.11)0.09(0.03,0.23)
孕期增重(kg)13 ± 5.65
胎次初产妇156 (57.6)0.04 (0.03,0.08)0.640.07 (0.03,0.18)0.52
经产妇108 (39.9)0.05 (0.03,0.10)0.07 (0.03,0.27)
胎龄<37 (未足月)29 (10.7)0.03 (0.02,0.07)0.360.06 (0.03,0.39)0.87
≥37 (足月)237 (87.5)0.04 (0.03,0.09)0.07 (0.03,0.18)
职业单位职员136 (50.2)0.04 (0.03,0.09)0.870.07 (0.03,0.23)0.92
产业工人18 (6.64)0.04 (0.03,0.09)0.06 (0.03,0.13)
服务业人员30 (11.1)0.04 (0.02,0.09)0.06 (0.03,0.38)
其它83 (30.6)0.05 (0.03,0.10)0.07 (0.03,0.18)
分娩方式自然产155 (57.2)0.05 (0.03,0.09)0.710.07 (0.03,0.18)0.78
剖宫产112 (41.3)0.04 (0.03,0.09)0.06 (0.03,0.28)
孕期被动吸烟75 (27.7)0.05 (0.03,0.09)0.130.07 (0.04,0.25)0.43
173 (63.8)0.04 (0.03,0.09)0.07 (0.03,0.20)
孕期饮酒6 (2.21)0.02 (0.00,0.06)0.100.06 (0.01,0.30)0.52
173 (63.8)0.04 (0.03,0.08)0.07 (0.03,0.19)
孕期每周食用水产品次数1 ~ 3次208 (76.8)0.04 (0.03,0.09)0.820.07 (0.03,0.21)0.54
3次以上32 (11.8)0.04 (0.03,0.09)0.06 (0.03,0.17)
饮用水来源自来水168 (62)0.04 (0.03,0.14)<0.010.07 (0.03,0.24)0.15
纯净水82 (30.3)0.03 (0.02,0.07)0.06 (0.03,0.17)
其他22(8.1)
受教育水平大专及以下143 (52.8)0.04 (0.02,0.07)0.940.07 (0.03,0.23)0.52
本科及以上111 (50)0.04 (0.02,0.08)0.08 (0.03,0.16)
新生儿出生指标
性别153 (56.5)0.04 (0.02,0.13)0.320.07 (0.03,0.22)0.58
104 (38.4)0.05 (0.03,0.08)0.07 (0.03,0.18)
胎龄271 ± 11.0
出生体重(kg)3.10 ± 0.44
出生体长(cm)49.1 ± 2.29
出生头围(cm)32.5 ± 2.57
), ArticleFig(id=1241408733763400416, tenantId=1146029695717560320, journalId=1234093305789726721, articleId=1241408718802317576, language=CN, label=表4, caption=

母婴人口学特征及分组OCPs分布(n=271)

, figureFileSmall=null, figureFileBig=null, tableContent=
母婴人口学特征胎粪中主要OCPs按人口学特征分组浓度(nmol/g)
特征指标均值±标准差频率(%)p,p'-DDE中值(P25P75)PΣ10OCPs中值(P25P75)P
年龄≤ 2530 ± 4.5028 (10.3)0.04 (0.02,0.11)0.400.07 (0.03,0.4)0.14
26 ~ 34197 (72.7)0.04 (0.03,0.08)0.07 (0.03,0.2)
≥ 3546 (17)0.05(0.03,0.11)0.10 (0.03,0.37)
孕前BMI(kg/m2)< 18.521 ± 2.9043 (15.9)0.04(0.03,0.06)0.310.05(0.03,0.21)0.67
18.5 ~ 23.9178 (65.7)0.04 (0.03,0.09)0.07 (0.03,0.18)
≥ 2434 (12.6)0.05 (0.03,0.11)0.09(0.03,0.23)
孕期增重(kg)13 ± 5.65
胎次初产妇156 (57.6)0.04 (0.03,0.08)0.640.07 (0.03,0.18)0.52
经产妇108 (39.9)0.05 (0.03,0.10)0.07 (0.03,0.27)
胎龄<37 (未足月)29 (10.7)0.03 (0.02,0.07)0.360.06 (0.03,0.39)0.87
≥37 (足月)237 (87.5)0.04 (0.03,0.09)0.07 (0.03,0.18)
职业单位职员136 (50.2)0.04 (0.03,0.09)0.870.07 (0.03,0.23)0.92
产业工人18 (6.64)0.04 (0.03,0.09)0.06 (0.03,0.13)
服务业人员30 (11.1)0.04 (0.02,0.09)0.06 (0.03,0.38)
其它83 (30.6)0.05 (0.03,0.10)0.07 (0.03,0.18)
分娩方式自然产155 (57.2)0.05 (0.03,0.09)0.710.07 (0.03,0.18)0.78
剖宫产112 (41.3)0.04 (0.03,0.09)0.06 (0.03,0.28)
孕期被动吸烟75 (27.7)0.05 (0.03,0.09)0.130.07 (0.04,0.25)0.43
173 (63.8)0.04 (0.03,0.09)0.07 (0.03,0.20)
孕期饮酒6 (2.21)0.02 (0.00,0.06)0.100.06 (0.01,0.30)0.52
173 (63.8)0.04 (0.03,0.08)0.07 (0.03,0.19)
孕期每周食用水产品次数1 ~ 3次208 (76.8)0.04 (0.03,0.09)0.820.07 (0.03,0.21)0.54
3次以上32 (11.8)0.04 (0.03,0.09)0.06 (0.03,0.17)
饮用水来源自来水168 (62)0.04 (0.03,0.14)<0.010.07 (0.03,0.24)0.15
纯净水82 (30.3)0.03 (0.02,0.07)0.06 (0.03,0.17)
其他22(8.1)
受教育水平大专及以下143 (52.8)0.04 (0.02,0.07)0.940.07 (0.03,0.23)0.52
本科及以上111 (50)0.04 (0.02,0.08)0.08 (0.03,0.16)
新生儿出生指标
性别153 (56.5)0.04 (0.02,0.13)0.320.07 (0.03,0.22)0.58
104 (38.4)0.05 (0.03,0.08)0.07 (0.03,0.18)
胎龄271 ± 11.0
出生体重(kg)3.10 ± 0.44
出生体长(cm)49.1 ± 2.29
出生头围(cm)32.5 ± 2.57
), ArticleFig(id=1241408734027641589, tenantId=1146029695717560320, journalId=1234093305789726721, articleId=1241408718802317576, language=EN, label=Table 5, caption=

Concentration levels of sex hormones in neonatal meconium (nmol/g, n = 271)

, figureFileSmall=null, figureFileBig=null, tableContent=
性激素检出率(%)性激素浓度(中值,P25P75)P
总体新生儿男性新生儿女性新生儿
P499.31.8 (0.47,3.85)1.94 (0.34,4.04)1.46 (0.53,3.42)0.44
17-OHP17.7ndndnd
AED99.00.24 (0.10,0.62)0.27 (0.10,0.72)0.21 (0.11,0.49)0.19
T86.00.13 (0.05,0.25)0.14 (0.05,0.27)0.11 (0.03,0.25)0.15
E195.20.15 (0.10,0.26)0.16 (0.10,0.30)0.15 (0.10,0.23)0.78
E295.90.38 (0.19,0.61)0.34 (0.18,0.59)0.50 (0.23,0.64)<0.01
E395.28.24 (1.45,37.2)8.18 (0.80,40.0)7.83 (2.08,26.5)0.83
E2/T/1.71 (0.43,3.66)1.26 (0.38,3.11)2.12 (0.45,4.19)<0.01
), ArticleFig(id=1241408734262522637, tenantId=1146029695717560320, journalId=1234093305789726721, articleId=1241408718802317576, language=CN, label=表5, caption=

新生儿胎粪中性激素的浓度水平(nmol/g, n=271)

, figureFileSmall=null, figureFileBig=null, tableContent=
性激素检出率(%)性激素浓度(中值,P25P75)P
总体新生儿男性新生儿女性新生儿
P499.31.8 (0.47,3.85)1.94 (0.34,4.04)1.46 (0.53,3.42)0.44
17-OHP17.7ndndnd
AED99.00.24 (0.10,0.62)0.27 (0.10,0.72)0.21 (0.11,0.49)0.19
T86.00.13 (0.05,0.25)0.14 (0.05,0.27)0.11 (0.03,0.25)0.15
E195.20.15 (0.10,0.26)0.16 (0.10,0.30)0.15 (0.10,0.23)0.78
E295.90.38 (0.19,0.61)0.34 (0.18,0.59)0.50 (0.23,0.64)<0.01
E395.28.24 (1.45,37.2)8.18 (0.80,40.0)7.83 (2.08,26.5)0.83
E2/T/1.71 (0.43,3.66)1.26 (0.38,3.11)2.12 (0.45,4.19)<0.01
), ArticleFig(id=1241408734430294811, tenantId=1146029695717560320, journalId=1234093305789726721, articleId=1241408718802317576, language=EN, label=Table 6, caption=

GLM for factors influencing the content of sex hormones in neonatal meconium (n=271)

, figureFileSmall=null, figureFileBig=null, tableContent=
性激素影响因素标准化系数β (95%CI)P
AED孕前BMI0.05 (0.01,0.08)<0.01
T饮用水来源(自来水)-0.24 (-0.42,-0.07)<0.01
E1职业(产业工人)-0.24 (-0.46,-0.01)0.04
E2孕期饮酒(是)-0.62 (-1.02,-0.22)<0.01
E2/T孕期增重-0.3 2(-0.61,-0.02)0.03
), ArticleFig(id=1241408734568706856, tenantId=1146029695717560320, journalId=1234093305789726721, articleId=1241408718802317576, language=CN, label=表6, caption=

影响新生儿胎粪中性激素含量的广义线性回归模型(n=271)

, figureFileSmall=null, figureFileBig=null, tableContent=
性激素影响因素标准化系数β (95%CI)P
AED孕前BMI0.05 (0.01,0.08)<0.01
T饮用水来源(自来水)-0.24 (-0.42,-0.07)<0.01
E1职业(产业工人)-0.24 (-0.46,-0.01)0.04
E2孕期饮酒(是)-0.62 (-1.02,-0.22)<0.01
E2/T孕期增重-0.3 2(-0.61,-0.02)0.03
), ArticleFig(id=1241408734681953078, tenantId=1146029695717560320, journalId=1234093305789726721, articleId=1241408718802317576, language=EN, label=Table 7, caption=

Results of the GLM for the association between OCPs exposure and sex hormones in meconium (n=271)

, figureFileSmall=null, figureFileBig=null, tableContent=
性激素总体新生儿β (95%CI)P男性新生儿β (95%CI)P女性新生儿β (95%CI)P
p,p'-DDE
P48.91 (-2.85,20.68)0.1410.3 (-4.41,25)0.175.03 (-15.7,25.7)0.63
AED1.82 (0.34,3.29)0.021.43 (-0.43,3.29)0.302.91 (0.45,5.36)0.02
T1.31 (0.03,2.60)0.041.30 (-0.73,3.33)0.210.01 (-1.01,1.03)0.99
E10.55 (-0.98,2.08)0.480.88 (-1.65,3.41)0.501.37 (0.49,2.24)<0.01
E2-0.82 (-1.90,0.26)0.14-0.46 (-2.12,1.20)0.59-0.49 (-1.52,0.53)0.35
E38.68 (3.99,13.4)<0.019.12 (3.11,14.9)<0.019.70 (2.18,17.2)0.11
E2/T-23 (-44,-1.95)0.03-17.8 (-40.2,4.68)0.12-12.3 (-55.0,30.3)0.57
Σ10OCPs
P40.46 (-1.28,2.20)0.61-0.44 (-2.31,1.43)0.643.23 (-1.36,7.83)0.17
AED0.06 (-0.17,0.29)0.610.02 (-0.22,0.25)0.880.59 (-0.03,1.21)0.06
T0.04 (-0.15,0.22)0.710.06 (-0.20,0.31)0.67-0.05 (-0.28,0.18)0.68
E10.00 (-0.22,0.22)0.990.02 (-0.29,0.34)0.890.12 (-0.08,0.32)0.24
E2-0.07 (-0.23,0.09)0.39-0.02 (-0.23,0.19)0.87-0.25 (-0.46,-0.04)0.02
E30.46 (-0.25,1.18)0.960.32 (-0.46,1.09)0.421.77 (-0.02,3.57)0.53
E2/T-0.92 (-3.96,2.12)0.550.37 (-2.34,3.08)0.79-11.8 (-22.8,-0.84)0.03
), ArticleFig(id=1241408734895862595, tenantId=1146029695717560320, journalId=1234093305789726721, articleId=1241408718802317576, language=CN, label=表7, caption=

OCPs暴露与胎粪性激素的广义线性回归模型结果(n = 271)

, figureFileSmall=null, figureFileBig=null, tableContent=
性激素总体新生儿β (95%CI)P男性新生儿β (95%CI)P女性新生儿β (95%CI)P
p,p'-DDE
P48.91 (-2.85,20.68)0.1410.3 (-4.41,25)0.175.03 (-15.7,25.7)0.63
AED1.82 (0.34,3.29)0.021.43 (-0.43,3.29)0.302.91 (0.45,5.36)0.02
T1.31 (0.03,2.60)0.041.30 (-0.73,3.33)0.210.01 (-1.01,1.03)0.99
E10.55 (-0.98,2.08)0.480.88 (-1.65,3.41)0.501.37 (0.49,2.24)<0.01
E2-0.82 (-1.90,0.26)0.14-0.46 (-2.12,1.20)0.59-0.49 (-1.52,0.53)0.35
E38.68 (3.99,13.4)<0.019.12 (3.11,14.9)<0.019.70 (2.18,17.2)0.11
E2/T-23 (-44,-1.95)0.03-17.8 (-40.2,4.68)0.12-12.3 (-55.0,30.3)0.57
Σ10OCPs
P40.46 (-1.28,2.20)0.61-0.44 (-2.31,1.43)0.643.23 (-1.36,7.83)0.17
AED0.06 (-0.17,0.29)0.610.02 (-0.22,0.25)0.880.59 (-0.03,1.21)0.06
T0.04 (-0.15,0.22)0.710.06 (-0.20,0.31)0.67-0.05 (-0.28,0.18)0.68
E10.00 (-0.22,0.22)0.990.02 (-0.29,0.34)0.890.12 (-0.08,0.32)0.24
E2-0.07 (-0.23,0.09)0.39-0.02 (-0.23,0.19)0.87-0.25 (-0.46,-0.04)0.02
E30.46 (-0.25,1.18)0.960.32 (-0.46,1.09)0.421.77 (-0.02,3.57)0.53
E2/T-0.92 (-3.96,2.12)0.550.37 (-2.34,3.08)0.79-11.8 (-22.8,-0.84)0.03
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广州市新生儿有机氯农药暴露特征及与激素水平的关联性初探
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何婷 1, 2 , 蔡凤珊 2 , 唐斌 2 , 严骁 1, 2 , 廖其龙 2 , 秦瑞欣 2, 3, 4 , 马璐 1 , 谢春 1 , 郑晶 1, 2, *
中国环境科学 | 环境毒理与健康 2025,45(4): 2264-2275
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中国环境科学 | 环境毒理与健康 2025, 45(4): 2264-2275
广州市新生儿有机氯农药暴露特征及与激素水平的关联性初探
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何婷1, 2 , 蔡凤珊2, 唐斌2, 严骁1, 2, 廖其龙2, 秦瑞欣2, 3, 4, 马璐1, 谢春1, 郑晶1, 2, *
作者信息
  • 1.贵州医科大学公共卫生与健康学院,环境污染与疾病监控教育部重点实验室,贵州 贵阳 561113
  • 2.生态环境部华南环境科学研究所新污染物研究中心,生态环境部环境污染健康风险评价重点实验室,广东 广州 510655
  • 3.中国科学院广州地球化学研究所,有机地球化学国家重点实验室,广东 广州 510640
  • 4.中国科学院大学,北京 100049
  • 何婷(2000-),女,贵州毕节人,贵州医科大学硕士研究生,研究方向为环境与健康..

通讯作者:

* 责任作者,研究员,
A preliminary study on the exposure of organochlorine pesticides in neonates and their association with hormone levels in Guangzhou
Ting HE1, 2 , Feng-shan CAI2, Bin TANG2, Xiao YAN1, 2, Qi-long LIAO2, Rui-xing QIN2, 3, 4, Lu MA1, Chun XIE1, Jing ZHENG1, 2, *
Affiliations
  • 1.The Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang 561113, China
  • 2.The Key Laboratory of Environmental Pollution Health Risk Assessment, Ministry of Ecology and Environment of the People's Republic of China, Research Center of Emerging Contaminants, South China Institute of Environmental Sciences, Ministry of Ecology and Environment, Guangzhou 510655, China
  • 3.State Key Laboratory of Organic Geochemistry, Guangdong Provincial Key Laboratory of Environmental Protection and Resources Utilization, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, China
  • 4.University of Chinese Academy of Sciences, Beijing 100049, China
出版时间: 2025-04-20
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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.

有机氯农药  /  孕期暴露  /  胎粪  /  性激素  /  出生体格

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.

organochlorine pesticides  /  prenatal exposure  /  meconium  /  sex hormones  /  birth physical
何婷, 蔡凤珊, 唐斌, 严骁, 廖其龙, 秦瑞欣, 马璐, 谢春, 郑晶. 广州市新生儿有机氯农药暴露特征及与激素水平的关联性初探. 中国环境科学, 2025 , 45 (4) : 2264 -2275 .
Ting HE, Feng-shan CAI, Bin TANG, Xiao YAN, Qi-long LIAO, Rui-xing QIN, Lu MA, Chun XIE, Jing ZHENG. A preliminary study on the exposure of organochlorine pesticides in neonates and their association with hormone levels in Guangzhou[J]. China Environmental Science, 2025 , 45 (4) : 2264 -2275 .
近几十年来,我国经历了快速的发展阶段,化学工业产品和农药的大规模生产和使用导致环境中积累了大量污染物.有机氯农药(OCPs)曾广泛应用于农业和虫害控制领域,直至1983年我国禁止使用OCPs时,其历史累计产量已超40万t[1],占全球总产量的20%~30%[2].鉴于OCPs具有多种毒性且对生态环境存在负面影响,《关于持久性有机污染物的斯德哥尔摩公约》(2009年)将包括对,对'-二氯二苯三氯乙烷(p,p'-DDT)在内的有机污染物列入持久性有机污染物名单,并在全球范围内禁止生产和使用[3].然而由于OCPs具有高持久性和强生物蓄积性,其仍然存在于环境介质和人体中[3-7].近年来,包括中国在内的许多地区人群中OCPs呈下降趋势[8-9],但其代谢物对,对'-二氯二苯乙烯(DDE) 在人体组织中半衰期约为8.6年[10].OCPs对人体健康有不利影响[11],并且有诸多证据显示,OCPs能够通过胎盘屏障,产生不良妊娠结果[12]并引发早期生命阶段的毒性作用.OCPs的孕期暴露及其对母婴敏感人群,尤其是新生儿健康的潜在危害已成为备受关注的公共卫生议题.
孕期及发育中的胎儿对环境污染物尤为敏感,胎儿在此阶段接触有毒有害物质可能造成永久性的健康影响.即使在极低剂量下,OCPs也能产生作用,干扰胎儿的性发育、生长和生殖等重要生命过程[13].流行病学研究发现,产前暴露于OCPs可能增加儿童患代谢综合征的风险[14],产前低剂量二氯二苯基三氯乙烷(DDT)暴露与胎儿体格发育存在关联,可能导致其头围、出生体重[15]和出生身长降低[16],进而影响新生儿的体格指标[17-18];妊娠妇女接触OCPs,可能会导致出生低体重婴儿的患病率增加[12];脐带血清p,p'-DDE浓度与婴儿出生后6个月时的身体质量指数(BMI)评分降低有关[19].其暴露影响存在性别差异[20],内分泌干扰被认为是OCPs暴露导致这些不良反应的重要机制之一.OCPs可能破坏胎儿的性激素水平稳态[21-22],其与性激素之间的关联因性别而异.性激素属于类固醇激素,在妊娠进程和胎儿发育中发挥着关键作用,主要包括孕酮(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.在人类妊娠过程中,孕激素和雌激素水平的升高有助于子宫内膜增厚,并抑制子宫收缩,防止流产,确保胎儿的正常发育[23-24];雄激素则有助于调节孕期激素水平,维持孕期内分泌平衡,例如,在妊娠早期,雄激素中的T水平的增加可以作为E2合成的前体[25].细胞实验研究显示,OCPs可能会模拟激素的合成与分泌模式,激素受体可能是OCPs雌激素破坏作用的关键途径[26].动物实验表明,OCPs在各种组织中表现出激素活性,被认为是具有雌激素作用的内分泌干扰化学物质[27].然而,目前研究对于OCPs与性激素水平之间的关联尚未达成一致意见.
研究显示,中国成年人血液中p,p'-DDE的累积水平依旧显著高于韩国、美国和日本[8],但低于印度[28].这主要是由于在发达国家中,部分OCPs的禁用时间更早,早期中国在OCPs的大量生产与使用方面情况更为严重,从而暴露程度更高[8],而在印度DDT继续在疟疾等病媒控制领域使用[29].从空间分布上看,工农业发展较快的华东地区(渤海湾和长三角)和华南地区(珠江三角洲)是主要污染区域[30].作为DDT的主要代谢产物,广州市居民血清中的p,p'-DDE脂质含量甚至高达740.97ng/g[31].此外,在华南地区的母乳中检测到DDT含量处于较高水平,其中p,p'-DDE的平均浓度最高[9];且在广州市新生儿中普遍检测到p,p'-DDE,表明新生儿在孕期暴露于OCPs,这对当地居民的健康构成了威胁[32].胎粪是新生儿出生后的首次排便,它在妊娠第12~13周至出生期间逐渐积累,由水、脂质、蛋白质、胆汁酸、羊水残留物、酶和细菌等多种成分组成,能够反映新生儿在母体内长达6~7个月的暴露情况[33-35].本研究共纳入了在广州市长期居住的271对母婴,在入院分娩时收集了健康新生儿的胎粪样本,检测其中10种OCPs和7种性激素含量,旨在评估胎儿OCPs的暴露情况及其对性激素水平的影响,并初步探讨新生儿性激素水平在OCPs暴露与出生体格关系的作用.
在2019年12月至2020年5月期间,于广州市中山大学附属第六医院产科征集住院生产的产妇作为志愿者.召集志愿者时首先咨询孕妇过往病史,排除存在恶性肿瘤疾病或其它原因导致异常妊娠的母婴志愿者,共采集了271例新生胎粪样品.胎粪在新生儿出生后24h内,从尿布表面采集了新生儿首次排出的胎粪样本,并将其置于已灭菌的粪便采集器中.运送至实验室后,保存于-80℃超低温冰箱中,以备后续检测分析.本研究获得中山大学附属第六医院医学伦理委员会的审核批准.医护人员详细告知志愿者本研究的目的及意义,并在她们签署知情同意书的情况下完成了样本采集工作.
在采集样品的同时进行详细的问卷调查,获得每一位母亲志愿者的基本信息,主要包括个人信息(年龄、职业、身高、体重),孕期情况(是否被动吸烟、是否饮酒、饮用水来源、食用海产品次数),生育情况(胎次、分娩方式),患病史等信息,在胎儿分娩后,通过医院的医疗记录采集新生儿出生指标(性别、胎龄、出生身长、出生体重、出生头围).
仪器:Agilent 7890B气相色谱-三重四极杆串联质谱仪(GC-MS/MS,安捷伦,美国);AB SCIEX API 6500三重四极杆质谱仪(AB SCIEX,LC-MS/MS,美国);DB-5HT毛细管柱(15m×0.25mm,0.10μm)、DB-5MS毛细管柱(30m×0.25mm,0.25μm)(安捷伦,美国);Poroshell 120EC-C18(100×2.7mm,5μm,A)(安捷伦,美国);分析天平(安亭电子仪器厂,上海);涡旋振荡器(Scientific Industries,美国);2600TH超声机(上海安谱实验科技,中国);DL 6000B高速离心机(湘仪离心机仪器有限公司,中国);氮吹仪(Organomation,美国).
耗材及试剂:2mL和1.5mL PP离心管;2mL透明进样瓶;内衬管,超纯水,碳18(C18),异辛烷(ISO),正己烷(HEX),无水硫酸钠(Na2SO4),乙酸乙酯(EtAC),丙酮(ACE),乙腈(ACN),色谱纯甲醇(MeOH)均购自上海安谱实验科技有限公司(中国).
标准品:OCPs目标化合物标准品购自美国AccuStandard公司;性激素目标化合物标准品购自百灵威科技公司(J&K)和天津阿尔塔科技公司,目标化合物的基本信息见表1.
OCPs分析:称取25mg胎粪湿重样品至2mL离心管中,加入适量的研磨球.向2mL离心管中加入50μL同位素内标(OCPs内标质量浓度为100ng/mL),并在4℃冰箱中静置过夜.加入500μL HEX、EtAc (1:1,V/V)混合溶液,均质4min,超声处理20min,然后以10000r/min离心10min,提取上清液.重复该步骤3次,将所有上清液合并.将合并后的上清液转移至装有20mg C18和20mg无水硫酸钠的尖底离心管中进行净化,均质1min,离心取上清液.最后氮吹至近干,加入200μL异辛烷复溶,转移至带有内衬管的进样瓶中,待GC-MS/MS检测.
性激素分析:称取25mg胎粪湿重样品至2mL离心管中,加入MeOH、CAN、超纯水(2:2:1,V/V)的混合溶液500μL(含同位素标记内标混合物)进行蛋白质沉淀和固液萃取.样品均质4min,超声处理5min(冰水浴).重复该步骤3次后,合并上清液,并在-40℃下静置1h以去除脂质.将样品在4℃下以12000r/min离心15min后,取上清液转移至带有内衬管的进样瓶中,待LC-MS/MS检测.
OCPs使用安捷伦7890B GC-MS/MS进行分析,在电子轰击源(EI)下,通过多反应监测模式(MRM)进行定量分析,使用DB-5MS毛细管色谱柱(30m×0.25mm,0.25μm)分离目标化合物.载气采用高纯氦气,流速设置为1mL/min,离子源、四级杆和进样口温度分别设置为230,150和290℃.升温程序设为:初始温度100℃,平衡1min,以20℃/min升温至180℃,保持5min,最后以20℃/min升温至310℃,保持3min.采用无分流进样,进样量为1μL.
性激素分析采用AB SCIEX API 6500三重四极杆质谱仪进行分析,采用电喷雾电离源(ESI),在MRM模式下进行正、负离子监测,色谱柱使用Poroshell 120EC-C18 (100×2.7mm,5μm,Agilent)进行分离,流动相为0.2moL/L氟化铵水溶液(A)和0.2moL/L氟化铵甲醇溶液(B),总洗脱时间9min,流速为0.35mL/min,进样量5μL,柱温40℃.梯度洗脱程序为:0~2min,20% B;2~7min,100% B;7.0~7.1min,100% B;7.1~9min,50% B.目标化合物及内标的质谱信息见表2.
方法回收率通过基质加标实验进行计算.加标设置方式为:在基质样品中加入10ng的OCPs和100ng性激素目标化合物.在胎粪基质加标样本中,目标化合物的平均回收率60%~120%,相对标准差(RSD)均小于20%.为确保仪器检测方法的质量控制,每20个样品注入一次标准溶液;为监测仪器的质量,每10个样品注入一次程序空白以评估潜在的污染情况.各目标化合物采用不少于5个点的校正曲线进行定量分析,标准曲线回归方程相关性系数r应≥0.995.方法定量限(LOQ)定义为空白样品中目标化合物浓度均值的标准偏差的3倍;对于在空白样品中未检测到的分析物,LOQ定义为信噪比为10(S/N=10,见表3).
对于研究对象基本特征描述,连续变量服从正态分布用均数±标准差()描述,非正态分布变量采用中位数(M)和四分位数(P25P75)描述;分类变量则以频率(%)的形式描述.检出率大于50%的OCPs被纳入后续统计分析,其他检出率低于50%的OCPs,以Σ10OCPs纳入统计分析.采用Mann-Whitney U检验(两组)和Kruskal-Wallis H检验(多组)比较不同人口学特征组OCPs暴露水平;采用Spearman秩相关分析计算胎粪性激素间的相关系数(r),置信水平α=0.05,置信区间(CI)取95%.本研究采用INTERGROWTH- 21st Project新生儿体型计算器,对出生大小指标进行胎龄Z标准化,计算出生体长- Z评分(BLZ)、出生体重- Z评分(BWZ)和出生头围- Z评分(HCZ).
采用广义线性模型(GLM)评估单一OCPs暴露与胎粪性激素及出生体格评分之间的关联.以OCPs暴露水平作为自变量,性激素和新生儿体格评分作为因变量,同时,母婴人口学特征作为控制变量纳入模型中;包括产妇孕前BMI (连续变量,kg/m2),孕期增重(连续变量,kg),产妇年龄(连续变量,岁),职业(分类变量),胎次(初产妇或经产妇),被动吸烟(是或否),孕期每周食用海产品次数(1~3次或3次以上),饮用水来源(自来水或纯净水),分娩方式(阴道分娩或剖腹产)和婴儿性别.模型用回归系数β值及95% CI描述OCPs暴露水平的剂量-反应关系.
为了进一步评估胎粪性激素在孕期OCPs暴露对新生儿体格评分影响的中介作用,采用中介效应模型分析OCPs暴露是否通过介导性激素水平引起新生儿出生体格评分变化.该模型通过建立暴露变量(OCPs)-中间变量(性激素)模型和暴露变量(OCPs)-结果(出生体格大小)模型,计算中介效应和总效应.利用IBM SPSS 26软件Process插件进行中介分析(model=4,bootstrap=5000)[36].进行中介分析的筛选条件如下:(1)暴露因素与中介因素间的关联具有统计学意义;(2)中介因素与结局因素的关联具有统计学意义;(3)暴露因素与结局因素的关联具有统计学意义;(4)暴露因素、中介因素及结局因素之三者的关联具有生理学基础[37].
母婴人口学特征见表4,孕妇的平均年龄为(30±4.5)岁,孕前BMI为(21.0±2.90) kg/m2,大多数孕妇的年龄在26~34岁之间,占72.7%;65.7%的孕妇保持正常孕前体重.产妇在孕期的平均增重为(13.1 ±5.65) kg;初产妇占57.6%,约50.2%的产妇职业为单位职员,57.2%的产妇选择自然分娩,27.7%的产妇在孕期接触被动吸烟,每周食用1~3次海产品的产妇占76.8%,60%的产妇饮用水来源为非纯净水,50%的产妇受过高等教育.新生儿的平均出生胎龄为(271±11) d,男性新生儿占56.5%.根据人口学特征进行分组后发现,饮用自来水的产妇其新生儿胎粪中p,p'-DDE浓度水平高于纯净水(P<0.05).研究表明,饮用水中有机污染物的污染水平依次为:水库水>自来水>桶装水>地下水>瓶装矿泉水,不同饮用水来源中污染物水平和成分存在差异[38].此外,自来水中农药的总浓度高于瓶装水,且在瓶装水中检测到的农药种类较少,饮用瓶装水作为主要的日常饮用水可能是人们避免农药潜在健康风险更好的选择[39].
本研究中,胎粪样品中只有p,p'-DDE的检出率超过50%,其浓度范围为nd~0.25nmol/g(中值0.05nmol/g).对比不同地区和国家新生儿胎粪中p,p'-DDE的水平发现,本研究胎粪中p,p'-DDE的浓度与澳大利亚(0.06nmol/g)相似[40],但高于韩国(0.04nmol/g)[34],台州路桥(浙江)(0.04nmol/g),杭州(浙江)(0.03nmol/g)和台州平桥(浙江)(0.03nmol/g)地区新生儿胎粪浓度[41].
新生儿胎粪中性激素的浓度分布情况如表5所示.本研究胎粪样本中17-OHP检出率低于50%,因此未对其进行统计分析.总人群胎粪性激素中位值含量由高到低依次为E3(8.24nmol/g)>P4 (1.80nmol/g)>E2 (0.38nmol/g)>AED (0.24nmol/g)>E1(0.15nmol/g)>T(0.13nmol/g).男性新生儿的E2及E2/T水平低于女性新生儿(P<0.05),研究表明,E2/T比值可以反映CYP19A1酶的活性,其比值的增加和减少分别指示酶活性的上调和下调,从而反映雄激素与雌激素之间的平衡变化[42-43].性激素的结构式及合成途径及其激素之间的相关性见图1.胎粪性激素间Spearman秩相关系数范围为-0.12~0.54,其中雌激素E1与E3的相关性最强(r=0.54,P<0.05),其次是雄激素T与AED的相关性(r=0.51,P<0.05).
通过纳入所有人口学特征指标,采用GLM初步筛选与性激素水平相关的主要因素,具有统计学意义的结果如表6所示.产妇的职业、孕前BMI、饮用水来源、孕期饮酒和孕期增重均可能影响后代胎粪中性激素水平,因此在后续GLM分析中均纳入人口学特征参数以调整胎儿OCPs暴露与胎粪性激素水平和出生体格评分的剂量-反应关系.
图2所示,对于总体新生儿而言,胎粪中Σ10OCPs浓度每增加1nmol/g,BWZ减少0.11(95%CI: -0.18,-0.04);HCZ减少0.17 (95%CI:-0.26,-0.08);按新生儿性别分层,胎粪中p,p'-DDE浓度每增加1nmol/g,男性新生儿BLZ增加3.29(95%CI: 0.67,5.92),胎粪中Σ10OCPs浓度每增加1nmol/g,男性新生儿BWZ和HCZ分别减少0.10(95%CI:-0.20,-0.01)和0.16 (95%CI:-0.28,-0.05);胎粪中Σ10OCPs浓度每增加1nmol/g,女性新生儿BWZ和HCZ分别减少0.21 (95%CI:-0.43,-0.08)和0.28 (95%CI:-0.44,-0.12).
表7所示,对于总体新生儿而言,p,p'-DDE浓度每增加1nmol/g,E2/T减少23nmol/g (95%CI: -44,-1.95),而AED、T和E3分别增加1.82nmol/g (95%CI:0.34,3.29)、1.31nmol/g (95%CI:0.03,2.60)和8.68nmol/g(95%CI:3.99,13.38).对于男性新生儿,p,p'-DDE浓度每增加1nmol/g,E3增加9.12nmol/g (95%CI:3.11,14.9);对于女性新生儿,p,p'-DDE浓度每增加1nmol/g,AED增加2.91nmol/g (95%CI: 0.45,5.36).此外,对于女性新生儿,当Σ10OCPs浓度每增加1nmol/g,E2和E2/T分别减少0.25nmol/g (95%CI:-0.46,-0.04)和11.8nmol/g(95%CI:-22.8,-0.84).
图3所示,对于总体新生儿而言,E3浓度每增加1nmol/g,BLZ增加0.11 (95%CI:0.03,0.18),T水平每增加1nmol/g,BLZ增加0.32 (95%CI:0.04,0.60).相比之下E2水平每增加1nmol/g,HCZ减少-0.50(95%CI:-0.88,-0.13);对于男性新生儿,E2水平每增加1nmol/g,BLZ、BWZ、HCZ分别减少-0.52(95%CI:-0.92,-0.11)、-0.39 (95%CI:-0.71,-0.07)、-0.75 (95%CI:-1.14,-0.36) ;对于女性新生儿,E2/T浓度每增加1nmol/g,女性新生儿HCZ减少-0.04(95%CI:-0.07,-0.01).
根据OCPs和胎粪性激素与新生儿出生体格Z评分的关联结果,筛选出符合条件的通路并进行了中介效应分析,中介路径如图4所示.p,p'-DDE暴露通过调节中介变量E3对男性新生儿的BLZ产生了正向的间接影响,间接效应为0.73,在p,p'-DDE暴露对男性新生儿BLZ影响的总效应中,有25.3%是通过调节中介变量E3实现.∑10OCPs暴露通过调节E2/T对女性新生儿的HCZ产生了负向的间接影响,间接效应为-0.18,在∑10OCPs暴露对女性新生儿HCZ的总效应中,有19.4%是通过调节中介变量E2/T来实现的.
研究表明大多数OCPs对激素受体具有亲和力,包括雄激素受体、雌激素受体或芳烃受体[44-45],因此,OCPs可以模拟或阻断天然激素的作用,干扰激素的合成、运输、代谢和排泄[46-47],这一现象在男性中表现得更为明显[48].本研究中p,p'-DDE与雌激素和雄激素呈正相关,表明孕期暴露于OCPs对胎儿性激素水平的具有干扰作用.p,p'-DDE具有稍弱的雌激素活性及抗雄激素活性[37],由于雄激素水平的升高可能是由p,p'-DDE阻断AR引起的[48-49],结合本研究中Σ10OCPs与女性新生儿的E2/T值呈负相关,提示p,p'-DDE孕期暴露与体内CYP19A1酶活性的效应关系具有性别差异.现有的流行病学研究尚未就OCPs暴露对性激素的具体影响达成一致结论[50].在不同地区的多项研究中,OCPs暴露对性激素的影响呈现出不同的结果:例如,于DDT或DDE的男性的T水平显著升高[49],产前OCPs暴露可观察到新生儿E2水平增加[51];日本北海道一项产前孕妇OCPs暴露和脐血类固醇激素相关性的研究显示,p,p'- DDE与雄激素和E2/T的比例呈正相关[42].丹麦的另一项研究发现宫内暴露于p,p'-DDE与男性生殖激素水平没有统计学意义相关[52].目前尚未发现研究关注OCPs暴露对胎粪性激素水平的影响.尽管如此,本研究表明,胎粪或许是一种较有潜力的非侵入性方式用于监测OCPs暴露情况.
孕期性激素稳态对维持母婴健康具有重要的作用.孕期胎盘触发母体和胎儿的下丘脑-垂体-性腺轴,以此调节母体和胎儿的生理机能.性激素是通过一列逐步的酶促反应从母体和胎儿的胆固醇中衍生出来的,它能够维持妊娠并参与胎儿发育轨迹[53].因此,在孕期任何阶段偏离正常性激素合成和信号传导都可能对母婴健康产生持久影响[54].新生儿的体格测量和激素稳态是识别新生儿生长障碍和疾病风险的重要依据[12].本研究对OCPs暴露与新生儿出生体格评分关联中性激素的中介作用进行了探索,结果表明男性新生儿出生体格更容易受到性激素水平影响,并且E3可能在OCPs对新生儿出生头围评分的影响中起到中介作用.然而,OCPs的内分泌干扰功能并非仅限于E3,目前尚不能确定OCPs是否会干扰类固醇激素代谢的路径及上下游生理过程,进而损害胎儿的生长发育.孕期是新生儿污染物暴露的敏感窗口期,容易引发生命早期的毒性作用.鉴于OCPs可能对新生儿产生影响,了解其环境来源显得十分重要.研究表明,OCPs在环境中可以吸附在悬浮颗粒或沉积物上,并在特定条件下重新释放回水体.华南地区一些水源地的几乎所有水样中都检测到了多种OCPs[55-56],提示母亲饮用自来水或许是新生儿接触OCPs的一个潜在来源[57],考虑到OCPs长期暴露可能带来的危害,仍然有必要继续严格控制并尽可能消除环境中的OCPs暴露.
3.1 广州市新生儿普遍暴露于p,p'-DDE.母亲孕期饮用水来源可能是新生儿OCPs暴露的一个潜在的影响因素.
3.2 OCPs与E2/T值呈负相关,与性激素水平呈现正相关,表明OCPs暴露可能影响新生儿性激素水平.
3.3 胎粪性激素在孕期OCPs暴露与新生儿出生体格评分的关联之间存在中介作用,提示OCPs可能通过改变胎儿性激素水平影响新生儿出生结局.
  • 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)
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2025年第45卷第4期
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  • 接收时间:2024-10-14
  • 首发时间:2026-03-19
  • 出版时间:2025-04-20
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  • 收稿日期:2024-10-14
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)
作者信息
    1.贵州医科大学公共卫生与健康学院,环境污染与疾病监控教育部重点实验室,贵州 贵阳 561113
    2.生态环境部华南环境科学研究所新污染物研究中心,生态环境部环境污染健康风险评价重点实验室,广东 广州 510655
    3.中国科学院广州地球化学研究所,有机地球化学国家重点实验室,广东 广州 510640
    4.中国科学院大学,北京 100049

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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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