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Hypothalamic-pituitary-ovarian axis perturbation in the basis of bisphenol A (BPA) reproductive toxicity in female zebrafish (Danio rerio)
Ecotoxicology and Environmental Safety ( IF 6.8 ) Pub Date : 2018-03-14 , DOI: 10.1016/j.ecoenv.2018.03.029
Ana Molina , Nieves Abril , Noelia Morales-Prieto , José Monterde , Nahúm Ayala , Antonio Lora , Rosario Moyano

Thousands of safety-related studies have been published on bisphenol A (BPA), an ubiquitous environmental pollutant with estrogenic activity and many other potential biological effects. In recent years, BPA exposure has been shown to cause anovulation and infertility through irreversible alteration of the hypothalamic-pituitary-gonadal axis in several organisms, including fish and mammals. Recently, the European Chemical Agency classified BPA as a “substance of very high concern” because of its endocrine-disrupting properties, which have serious effects on human health. Given the risk of exposure to BPA as a pollutant in the environment, food, and drinking water, the objective of our study was to assess the effects of this compound on the adeno-hypophysis by means of a histopathological and morphometric study of the gonadotroph cells. In addition, using quantitative real-time PCR (qRT-PCR) assays, we analyzed the changes in the expression of Cyp19b (an aromatase gene). Zebrafish were randomly distributed into five groups: a control group and 4 treated groups which were exposed to different BPA concentrations (1, 10, 100 and 1000 µg/L). The effects of the different doses on Cyp19b mRNA molecules followed a non-monotonic curve, with the 1 and 1000 µg/L doses causing dramatic decreases in the number of Cyp19b transcripts while the doses of 10 and 100 µg/L caused important increases. The consequences might be deregulation of gonadotropic hormones causing degeneration of gonadotropic cells, as observed in BPA treated animals. This is the first study in which the gonadotroph cells have been evaluated using histomorphological endpoints after BPA exposure in zebrafish.



中文翻译:

基于双酚A(BPA)对雌性斑马鱼(Danio rerio)生殖毒性的下丘脑-垂体-卵巢轴微扰

关于双酚A(BPA)的安全性研究已经发表了数千篇,双酚A是一种普遍存在的环境污染物,具有雌激素活性和许多其他潜在的生物学效应。近年来,已显示双酚A暴露通过包括鱼和哺乳动物在内的几种生物体的下丘脑-垂体-性腺轴的不可逆改变而引起无排卵和不孕。最近,欧洲化学局将BPA归类为“高度关注的物质”,因为它具有破坏内分泌的特性,会对人体健康造成严重影响。考虑到环境,食物和饮用水中BPA作为污染物暴露的风险,我们的研究目的是通过对性腺营养细胞的组织病理学和形态学研究来评估该化合物对腺垂体的影响。此外,使用定量实时PCR(qRT-PCR)分析,我们分析了Cyp19b(芳香酶基因)表达的变化。斑马鱼随机分为5组:对照组和4个治疗组,分别暴露于不同的BPA浓度(1、10、100和1000 µg / L)。不同剂量对Cyp19b mRNA的影响遵循非单调曲线,分别以1和1000 µg / L的剂量引起Cyp19b mRNA数量的急剧减少。Cyp19b转录本,而10和100 µg / L的剂量会引起重要的增加。如在BPA处理的动物中观察到的那样,其后果可能是促性腺激素失调导致促性腺细胞变性。这是第一项研究,在斑马鱼中BPA暴露后,使用组织形态学终点评估了性腺营养细胞。

更新日期:2018-03-14
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