Cheon Yong-Pil
Division of Developmental Biology and Physiology, Dept. of Biotechnology, Sungshin University, Seoul 02844, Korea.
Dev Reprod. 2020 Mar;24(1):1-17. doi: 10.12717/DR.2020.24.1.1. Epub 2020 Mar 31.
Phthalates have a long industrial history. It is suspected that phthalates and their metabolites have detrimental effects on reproduction and development. They are well-known for their anti-androgenic effects. Several studies have indicated that phthalates and their metabolites are reprotoxic in males and endocrine disruptors. Reproduction and embryogenesis occur in the uterus of female eutherian mammals. A horizontal analytical method is preferred to elucidate the toxic effects of phthalates on human reproduction. Nevertheless, there are vast numbers of known phthalates and not all of their modes of action have been clarified. Di-(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer and has been the subject of numerous toxicological studies. However, few of these have reported on the toxic effects of DEHP, its metabolites, other phthalates, or mixtures on female reproduction. Acute and high doses of DEHP adversely affect uterine histology. Recently, it was disclosed that chronic exposures to low doses of DEHP have endocrine disruption efficacy. DEHP induces various cellular responses including modulation of the expression and regulation of steroid hormone receptors and transcription and paracrine factors. Uteri do not respond uniformly to DEHP exposure. The phenotypic manifestations and effects on fertility in response to DEHP and its metabolites may vary with species, developmental stage, and generation. Hence, DEHP exposure may histological alter the uterus and induce endometriosis, endometriosis, hyperplasia, myoma, and developmental and reproductive toxicity.
邻苯二甲酸盐有着悠久的工业历史。人们怀疑邻苯二甲酸盐及其代谢物对生殖和发育有有害影响。它们以抗雄激素作用而闻名。多项研究表明,邻苯二甲酸盐及其代谢物对男性具有生殖毒性且是内分泌干扰物。有胎盘类雌性哺乳动物的生殖和胚胎发生在子宫内。一种横向分析方法更适合用于阐明邻苯二甲酸盐对人类生殖的毒性作用。然而,已知的邻苯二甲酸盐数量众多,并非所有的作用模式都已明确。邻苯二甲酸二(2-乙基己基)酯(DEHP)是一种常用的增塑剂,并且一直是众多毒理学研究的对象。然而,其中很少有研究报告DEHP、其代谢物、其他邻苯二甲酸盐或混合物对雌性生殖的毒性作用。急性和高剂量的DEHP会对子宫组织学产生不利影响。最近,有研究表明长期低剂量接触DEHP具有内分泌干扰作用。DEHP会引发各种细胞反应,包括调节类固醇激素受体的表达和调控以及转录和旁分泌因子。子宫对DEHP暴露的反应并不一致。DEHP及其代谢物对生育能力的表型表现和影响可能因物种、发育阶段和代际而有所不同。因此,接触DEHP可能会在组织学上改变子宫并诱发子宫内膜异位、增生、肌瘤以及发育和生殖毒性。