Department of Environmental Toxicology, Uppsala University, Uppsala, Sweden.
Department of Environmental Medicine and Public Health, Centre for Reproductive Biology in Uppsala (CRU), Uppsala, Sweden.
J Toxicol Environ Health A. 2020 Jan 17;83(2):66-81. doi: 10.1080/15287394.2020.1728598. Epub 2020 Feb 20.
Bisphenol A (BPA) and phthalate diesters are ubiquitous environmental contaminants. While these compounds have been reported as reproductive toxicants, their effects may partially be attributed to metabolites. The aim of this study was to examine reproductive organ development in chicken embryos exposed to the BPA metabolite, 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP; 100 µg/g egg) or a human-relevant mixture of 4 phthalate monoesters (85 µg/g egg). The mixture was designed within the EU project EDC-MixRisk based upon a negative association with anogenital distance in boys at 21 months of age in a Swedish pregnancy cohort. Chicken embryos were exposed from an initial stage of gonad differentiation (embryonic day 4) and dissected two days prior to anticipated hatching (embryonic day 19). No discernible effects were noted on reproductive organs in embryos exposed to the mixture. MBP-treated males exhibited retention of Müllerian ducts and feminization of the left testicle, while MBP-administered females displayed a diminished the left ovary. In the left testicle of MBP-treated males, mRNA expression of female-associated genes was upregulated while the testicular marker gene SOX9 was downregulated, corroborating a feminizing effect by MBP. Our results demonstrate that MBP, but not the phthalate monoester mixture, disrupts both male and female reproductive organ development in an avian embryo model.
双酚 A(BPA)和邻苯二甲酸酯二酯是普遍存在的环境污染物。虽然这些化合物已被报道为生殖毒物,但它们的影响可能部分归因于代谢物。本研究的目的是研究暴露于 BPA 代谢物 4-甲基-2,4-双(4-羟基苯基)戊-1-烯(MBP;100µg/g 卵)或人类相关的邻苯二甲酸单酯混合物(85µg/g 卵)的鸡胚胎生殖器官发育。该混合物是根据瑞典妊娠队列中男孩在 21 个月龄时与肛门生殖器距离呈负相关的欧盟项目 EDC-MixRisk 设计的。鸡胚胎从性腺分化的初始阶段(胚胎第 4 天)开始暴露,然后在预期孵化前两天(胚胎第 19 天)进行解剖。暴露于混合物的胚胎的生殖器官没有明显的影响。MBP 处理的雄性表现出缪勒管的保留和左侧睾丸的女性化,而 MBP 处理的雌性表现出左侧卵巢的缩小。在 MBP 处理的雄性左侧睾丸中,女性相关基因的 mRNA 表达上调,而睾丸标记基因 SOX9 下调,证实 MBP 具有女性化作用。我们的研究结果表明,MBP 而不是邻苯二甲酸单酯混合物,会破坏禽类胚胎模型中雄性和雌性生殖器官的发育。