Warembourg C, Debost-Legrand A, Bonvallot N, Massart C, Garlantézec R, Monfort C, Gaudreau E, Chevrier C, Cordier S
Institut national de la santé et de la recherche médicale (Inserm), U1085, Institut de recherche en santé, environnement et travail (Irset), F-35043 Rennes, France Université de Rennes 1, F-35043 Rennes, France
Institut national de la santé et de la recherche médicale (Inserm), U1085, Institut de recherche en santé, environnement et travail (Irset), F-35043 Rennes, France Centre Hospitalier Universitaire de Clermont-Ferrand, Service de Santé Publique, F-63000 Clermont-Ferrand, France Centre Hospitalier Universitaire de Clermont-Ferrand, EA 4681, PEPRADE, Université d'Auvergne, F-63000 Clermont-Ferrand, France.
Hum Reprod. 2016 Jan;31(1):190-8. doi: 10.1093/humrep/dev260. Epub 2015 Oct 22.
Is prenatal exposure to persistent organic pollutants (POPs) associated with variations of sex hormone levels in cord blood?
Prenatal exposure to a number of POPs is associated with a disruption of hormone levels in cord blood, with sex specificities.
Epidemiological studies have reported disorders of reproductive health, in relation with POPs exposure during early life and the endocrine disruption properties of these chemicals have been suggested as possible mechanisms.
STUDY DESIGN, SIZE, DURATION: A subset of 282 mother-child pairs was selected from the prospective population-based PELAGIE birth cohort (n = 3421, 2002-2006, Brittany, France). Pregnant women were recruited before 19 weeks of gestation and followed until delivery.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Sex hormone levels including sex hormone-binding globulin (SHBG), estradiol (E2), total testosterone (T), free testosterone (fT = T/SHBG) and the aromatase index (AI = T/E2) were measured in 282 cord blood samples. Anti-Müllerian hormone (AMH) was measured in male newborns only. Pesticide concentrations of α-endosulfan, β-hexachlorocyclohexane (β-HCH), γ-HCH, dieldrin, pp'-dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), heptachlor epoxide (HCE), as well as PCBs (congeners 153, 187 and the sum of anti-estrogenic PCBs 118, 138, and 170) and decabrominated diphenyl ether (BDE209) were also measured in cord blood. Associations between sex hormones and POPs exposure were explored using multiple linear regressions adjusted for potential confounders.
High PCB levels were associated with an increase of SHBG (P-trend < 0.01) and AMH (P-trend < 0.05) and a decrease of fT (P-trend < 0.05) and AI (P-trend < 0.01). High pesticide levels, particularly α-endosulfan and HCE, were associated with an increase of SHBG (P < 0.05) and E2 (P < 0.01) and a decrease of fT (P < 0.05) and AI (P < 0.01). Several of these associations were stronger, or specific, among male or female newborns. The associations were not altered in the sensitivity analyses.
LIMITATIONS, REASONS FOR CAUTION: The study population was of relatively small sample size, and some compounds rarely detected in cord blood. The high level of correlation between POPs makes it difficult to identify the most contributing POPs. Hormone measurements were performed at birth (in cord blood) and may not adequately represent the infant endocrine system. Multiple statistical testing may have led to false-positive associations.
Our results are in discordance with those reported in the only published study of the kind but in accordance with studies about prenatal exposure to other endocrine disruptors such as phthalates. These findings may help understanding the pathways involved in adverse reproductive outcomes associated with POPs exposure.
STUDY FUNDING/COMPETING INTERESTS: The PELAGIE cohort is funded by Inserm, French Ministry of Health, French Ministry of Labor, InVS, ANR, ANSES, and French Ministry of Ecology. None of the authors has any competing interest to declare.
产前暴露于持久性有机污染物(POPs)是否与脐血中激素水平的变化有关?
产前暴露于多种持久性有机污染物与脐血中激素水平的紊乱有关,且存在性别特异性。
流行病学研究报告了早期生活中接触持久性有机污染物与生殖健康紊乱有关,并且这些化学物质的内分泌干扰特性被认为是可能的机制。
研究设计、规模、持续时间:从基于人群的前瞻性PELAGIE出生队列(n = 3421,2002 - 2006年,法国布列塔尼)中选取了282对母婴。孕妇在妊娠19周前招募,并随访至分娩。
参与者/材料、环境、方法:在282份脐血样本中测量了性激素水平,包括性激素结合球蛋白(SHBG)、雌二醇(E2)、总睾酮(T)、游离睾酮(fT = T/SHBG)和芳香化酶指数(AI = T/E2)。仅在男性新生儿中测量了抗苗勒管激素(AMH)。还测量了脐血中α - 硫丹、β - 六氯环己烷(β - HCH)、γ - 六氯环己烷、狄氏剂、对,对'-二氯二苯二氯乙烯(p,p'-DDE)、六氯苯(HCB)、环氧七氯(HCE)等农药浓度,以及多氯联苯(同系物153、187和抗雌激素多氯联苯118、138和170的总和)和十溴二苯醚(BDE209)。使用针对潜在混杂因素进行调整的多元线性回归探索了性激素与持久性有机污染物暴露之间的关联。
高多氯联苯水平与SHBG升高(P趋势<0.01)和AMH升高(P趋势<0.05)以及fT降低(P趋势<0.05)和AI降低(P趋势<0.01)相关。高农药水平,特别是α - 硫丹和环氧七氯,与SHBG升高(P < 0.05)和E2升高(P < 0.01)以及fT降低(P < 0.05)和AI降低(P < 0.01)相关。其中一些关联在男性或女性新生儿中更强或具有特异性。在敏感性分析中,这些关联未改变。
局限性、注意事项:研究人群样本量相对较小,并且一些化合物在脐血中很少被检测到。持久性有机污染物之间的高度相关性使得难以确定最具影响的持久性有机污染物。激素测量在出生时(脐血中)进行,可能无法充分代表婴儿的内分泌系统。多次统计检验可能导致假阳性关联。
我们的结果与唯一一项已发表的此类研究报告的结果不一致,但与关于产前暴露于其他内分泌干扰物如邻苯二甲酸盐的研究一致。这些发现可能有助于理解与持久性有机污染物暴露相关的不良生殖结局所涉及的途径。
研究资金/利益冲突:PELAGIE队列由法国国家卫生与医学研究院(Inserm)、法国卫生部、法国劳动部、法国国家卫生监测所(InVS)、法国国家科研署(ANR)、法国食品安全局(ANSES)和法国生态部资助。作者均无利益冲突声明。