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邻苯二甲酸酯调节西方爪蟾胚胎中的甾体 5-还原酶转录本。

Phthalates modulate steroid 5-reductase transcripts in the Western clawed frog embryo.

机构信息

Chemistry and Chemical Engineering Department, Royal Military College of Canada, Kingston, ON, Canada.

Chemical Engineering Department, McGill University, Montreal, QC, Canada.

出版信息

Comp Biochem Physiol C Toxicol Pharmacol. 2018 Nov;213:39-46. doi: 10.1016/j.cbpc.2018.07.005. Epub 2018 Jul 25.

DOI:10.1016/j.cbpc.2018.07.005
PMID:30055282
Abstract

Phthalates are used worldwide in the manufacturing of plastics, added to cosmetic products, personal care products, pharmaceuticals, medical devices, and paints; and are widely detected in soil, surface water, and organism tissues. Phthalate esters have been previously shown to interfere with the endocrine system in vertebrates. However, few studies have investigated the effects of phthalates on testosterone-converting enzymes that affect hormone levels and reproduction. In the present study, we exposed the Western clawed frog (Silurana tropicalis) to 0.1, 1, and 10 μM diethylhexyl phthalate (DEHP), dibutyl phthalate (DBP), and diethyl phthalate (DEP) during early amphibian embryonic development. Additional DBP exposures were conducted ex vivo using mature frog testes. Malformations and mRNA levels of genes associated to reproduction and oxidative stress were evaluated. 0.1 μM DEHP, DBP, and DEP induced an array of malformations, including incomplete gut coiling, edemas, and eye malformations. Moreover, all three phthalates increased the expression of androgen-related genes, such as steroid-5α-reductase 1, 2, 3, steroid-5β-reductase, and androgen receptor at concentrations ranging from 0.1 to 10 μM depending on the phthalate and gene. Data suggest that the phthalate esters tested are teratogens to the amphibian embryo and that these phthalates exhibit an androgenic activity in amphibians.

摘要

邻苯二甲酸酯在全球范围内被用于制造塑料,添加到化妆品、个人护理产品、药品、医疗器械和涂料中;并且广泛存在于土壤、地表水和生物组织中。邻苯二甲酸酯已被证明会干扰脊椎动物的内分泌系统。然而,很少有研究调查邻苯二甲酸酯对影响激素水平和生殖的睾酮转化酶的影响。在本研究中,我们在早期两栖动物胚胎发育过程中使西部爪蟾(Silurana tropicalis)暴露于 0.1、1 和 10µM 的邻苯二甲酸二乙酯(DEHP)、邻苯二甲酸二丁酯(DBP)和邻苯二甲酸二乙酯(DEP)中。还使用成熟的青蛙睾丸进行了体外 DBP 暴露。评估了畸形和与生殖和氧化应激相关的基因的 mRNA 水平。0.1µM 的 DEHP、DBP 和 DEP 会引起多种畸形,包括不完全的肠道缠绕、水肿和眼睛畸形。此外,所有三种邻苯二甲酸酯都在 0.1 至 10µM 浓度范围内增加了与雄激素相关的基因的表达,如甾体 5α-还原酶 1、2、3、甾体 5β-还原酶和雄激素受体,这取决于邻苯二甲酸酯和基因。数据表明,所测试的邻苯二甲酸酯酯类对两栖动物胚胎具有致畸性,并且这些邻苯二甲酸酯类在两栖动物中表现出雄激素活性。

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Phthalates modulate steroid 5-reductase transcripts in the Western clawed frog embryo.邻苯二甲酸酯调节西方爪蟾胚胎中的甾体 5-还原酶转录本。
Comp Biochem Physiol C Toxicol Pharmacol. 2018 Nov;213:39-46. doi: 10.1016/j.cbpc.2018.07.005. Epub 2018 Jul 25.
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Androgens modulate gene expression and specific DNA methylation pattern of steroid 5α-reductases in the frog Silurana tropicalis.雄激素调节热带爪蟾中甾体5α-还原酶的基因表达和特定DNA甲基化模式。
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The teratogenicity and behavioral teratogenicity of di(2-ethylhexyl) phthalate (DEHP) and di-butyl phthalate (DBP) in a chick model.邻苯二甲酸二(2-乙基己基)酯(DEHP)和邻苯二甲酸二丁酯(DBP)在鸡模型中的致畸性和行为致畸性。
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Phthalate ester-induced gubernacular lesions are associated with reduced insl3 gene expression in the fetal rat testis.邻苯二甲酸酯诱导的引带损伤与胎鼠睾丸中胰岛素样肽3(Insl3)基因表达降低有关。
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