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孕期暴露于对羟基苯甲酸酯与迷你青春期的肛殖距和生殖激素:来自欧登塞儿童队列的一项研究。

Prenatal paraben exposure and anogenital distance and reproductive hormones during mini-puberty: A study from the Odense Child Cohort.

机构信息

Department of Pharmacology, Clinical Pharmacy and Environmental Medicine, University of Southern Denmark, Odense 5000, Denmark; Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen 2100, Denmark.

Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen 2100, Denmark; International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen 2100, Denmark.

出版信息

Sci Total Environ. 2021 May 15;769:145119. doi: 10.1016/j.scitotenv.2021.145119. Epub 2021 Jan 14.

Abstract

BACKGROUND

Parabens are added to personal care products as antimicrobial preservatives. They have been suggested to have endocrine disrupting abilities. Prenatal exposure to parabens has been associated with reproductive endpoints including reduced male anogenital distance (AGD, distance from anus to genitals), which is sensitive to prenatal anti-androgenic exposure.

OBJECTIVES

To study the associations between maternal paraben concentrations in second trimester urine and AGD and reproductive hormone concentrations at 3 months of age in offspring.

METHODS

Pregnant women from Odense, Denmark were included in early pregnancy from 2010 to 12, and their children are being followed up. Fasting spot urine samples from 536 pregnant women were analyzed for methylparaben (MeP), ethyl-paraben (EtP), iso-propylparaben (i-PrP), n-propylparaben (n-PrP), n-butylparaben (n-BuP) and benzylparaben (BzP) by liquid chromatography tandem mass spectrometry and thereafter osmolarity adjusted. Three months after expected date of birth, AGD was measured in 452 children, and serum concentrations of follicle stimulating hormone (FSH), luteinizing (LH), testosterone, dehydroepiandrosterone-sulphate (DHEAS), androstenedione and 17-hydroxyprogesterone (17-OHP) were measured in 198 children. Maternal paraben exposure was categorized into tertiles or below and above level of detection, and sex-stratified multiple linear regression analyses were performed with AGD or reproductive hormones as outcomes.

RESULTS

Most pregnant women had low concentrations of parabens in urine, but 10% exceeded the threshold for adverse estrogenic effects. Higher maternal paraben exposure was associated with shorter AGD in male offspring and longer AGD in girls, although only significant for MeP in boys. In addition, FSH, LH, DHEAS, 17-OHP concentrations were lower in girls with high prenatal paraben exposure, whereas no consistent pattern was found in boys.

DISCUSSION

The endocrine disrupting abilities of parabens may affect humans at vulnerable time periods during development, which may have long term impact on reproductive function. This is the first study to find these associations in girls and our findings need confirmation.

摘要

背景

对苯二甲酸酯作为抗菌防腐剂添加到个人护理产品中。它们具有内分泌干扰能力。产前暴露于对苯二甲酸酯与生殖终点有关,包括减少男性生殖器-肛门距离(AGD,肛门到生殖器的距离),这对产前抗雄激素暴露很敏感。

目的

研究孕妇妊娠中期尿液中对苯二甲酸酯浓度与后代 3 个月时 AGD 和生殖激素浓度之间的关系。

方法

2010 年至 12 月,丹麦奥登塞的孕妇在早期妊娠时被纳入研究,他们的孩子正在接受随访。对 536 名孕妇的空腹尿液样本进行了甲基对苯二甲酸酯(MeP)、乙基对苯二甲酸酯(EtP)、异丙基对苯二甲酸酯(i-PrP)、正丙基对苯二甲酸酯(n-PrP)、正丁基对苯二甲酸酯(n-BuP)和苄基对苯二甲酸酯(BzP)的分析,方法为液相色谱-串联质谱法,随后进行了渗透压调整。在预计出生日期后 3 个月,对 452 名儿童进行了 AGD 测量,对 198 名儿童进行了卵泡刺激素(FSH)、黄体生成素(LH)、睾丸激素、脱氢表雄酮硫酸盐(DHEAS)、雄烯二酮和 17-羟孕酮(17-OHP)的血清浓度测量。以 AGD 或生殖激素为结局,将母体对苯二甲酸酯暴露分为三分位或低于检测水平和高于检测水平,并进行了性别分层的多元线性回归分析。

结果

大多数孕妇尿液中对苯二甲酸酯浓度较低,但有 10%的孕妇超过了不良雌激素作用的阈值。母亲对苯二甲酸酯暴露水平较高与男婴的 AGD 较短和女孩的 AGD 较长有关,尽管仅在男孩中 MeP 有显著意义。此外,高产前对苯二甲酸酯暴露的女孩的 FSH、LH、DHEAS、17-OHP 浓度较低,而男孩则没有一致的模式。

讨论

对苯二甲酸酯的内分泌干扰能力可能在发育过程中的脆弱时期对人类产生影响,这可能对生殖功能产生长期影响。这是第一项在女孩中发现这些关联的研究,我们的研究结果需要进一步证实。

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