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全氟烷基物质对雄激素活性的内分泌干扰:临床和实验证据。

Endocrine Disruption of Androgenic Activity by Perfluoroalkyl Substances: Clinical and Experimental Evidence.

机构信息

Department of Medicine, Operative Unit of Andrology and Medicine of Human Reproduction, University of Padova, Padova, Italy.

Department of Neurosciences, University of Padova, Padova, Italy.

出版信息

J Clin Endocrinol Metab. 2019 Apr 1;104(4):1259-1271. doi: 10.1210/jc.2018-01855.

DOI:10.1210/jc.2018-01855
PMID:30403786
Abstract

BACKGROUND

Considerable attention has been paid to perfluoroalkyl compounds (PFCs) because of their worldwide presence in humans, wildlife, and environment. A wide variety of toxicological effects is well supported in animals, including testicular toxicity and male infertility. For these reasons, the understanding of epidemiological associations and of the molecular mechanisms involved in the endocrine-disrupting properties of PFCs on human reproductive health is a major concern.

OBJECTIVE

To investigate the relationship between PFC exposure and male reproductive health.

DESIGN

This study was performed within a screening protocol to evaluate male reproductive health in high schools.

PATIENTS

This is a cross-sectional study on 212 exposed males from the Veneto region, one of the four areas worldwide heavily polluted with PFCs, and 171 nonexposed controls.

MAIN OUTCOME MEASURES

Anthropometrics, seminal parameters, and sex hormones were measured in young males from exposed areas compared with age-matched controls. We also performed biochemical studies in established experimental models.

RESULTS

We found that increased levels of PFCs in plasma and seminal fluid positively correlate with circulating testosterone (T) and with a reduction of semen quality, testicular volume, penile length, and anogenital distance. Experimental evidence points toward an antagonistic action of perfluorooctanoic acid on the binding of T to androgen receptor (AR) in a gene reporter assay, a competition assay on an AR-coated surface plasmon resonance chip, and an AR nuclear translocation assay.

DISCUSSION

This study documents that PFCs have a substantial impact on human health as they interfere with hormonal pathways, potentially leading to male infertility.

摘要

背景

由于全氟烷基化合物(PFCs)在人类、野生动物和环境中的广泛存在,人们对其给予了相当多的关注。大量动物研究证实了 PFCs 具有广泛的毒理学效应,包括睾丸毒性和男性不育。基于这些原因,人们对 PFCs 对人类生殖健康的内分泌干扰特性的流行病学关联和分子机制的理解非常关注。

目的

研究 PFC 暴露与男性生殖健康之间的关系。

设计

本研究是在一项评估高中生男性生殖健康的筛查方案中进行的。

患者

这是一项横断面研究,共纳入了来自威尼托地区的 212 名暴露男性和 171 名非暴露对照,威尼托地区是全球四个 PFC 污染严重的地区之一。

主要观察指标

与年龄匹配的对照组相比,比较暴露区年轻男性的人体测量学、精液参数和性激素。我们还在已建立的实验模型中进行了生化研究。

结果

我们发现,血浆和精液中 PFCs 水平的升高与循环睾酮(T)水平升高以及精液质量下降、睾丸体积减小、阴茎长度减小和肛殖距减小呈正相关。实验证据表明,全氟辛酸(PFOA)在基因报告基因测定、AR 包被表面等离子体共振芯片上的竞争测定和 AR 核易位测定中对 T 与雄激素受体(AR)的结合具有拮抗作用。

讨论

本研究表明,PFCs 对人类健康有重大影响,因为它们干扰了激素途径,可能导致男性不育。

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