Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología "Isidro Espinosa de los Reyes" - Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México 11000, Mexico.
Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología "Isidro Espinosa de los Reyes" - Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México 11000, Mexico; Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana, Ciudad de México 04960, Mexico.
Environ Int. 2021 Jan;146:106228. doi: 10.1016/j.envint.2020.106228. Epub 2020 Nov 4.
Di(2-ethylhexyl) phthalate (DEHP) is a chemical widely distributed in the environment as is extensively used in the plastic industry. DEHP is considered an endocrine disruptor chemical (EDC) and humans are inevitably and unintentionally exposed to this EDC through several sources including food, beverages, cosmetics, medical devices, among others. DEHP exposure has been associated and may be involved in the development of various pathologies; importantly, pregnant women are a particular risk group considering that endocrine alterations during gestation may impact fetal programming leading to the development of several chronic diseases in adulthood. Recent studies have indicated that exposure to DEHP and its metabolite Mono(2-ethylhexyl) phthalate (MEHP) may impair placental development and function, which in turn would have a negative impact on fetal growth. Studies performed in several trophoblastic and placental models have shown the negative impact of DEHP and MEHP in key processes related to placental development such as implantation, differentiation, invasion and angiogenesis. In addition, many alterations in placental functions like hormone signaling, metabolism, transfer of nutrients, immunomodulation and oxidative stress response have been reported. Moreover, clinical-epidemiological evidence supports the association between DEHP exposure and adverse pregnancy outcomes and pathologies. In this review, we aim to summarize for the first time current knowledge about the impact of DEHP and MEHP exposure on placental development and pathophysiology, as well as the mechanisms involved. We also remark the importance of exploring DEHP and MEHP effects in different trophoblast cell populations and discuss new perspectives regarding this topic.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种广泛分布于环境中的化学物质，广泛应用于塑料工业。DEHP 被认为是一种内分泌干扰化学物质（EDC），人类不可避免地会通过食物、饮料、化妆品、医疗器械等多种来源无意中接触到这种 EDC。DEHP 暴露与各种病理学的发生有关，可能与之相关；重要的是，孕妇是一个特殊的风险群体，因为妊娠期间的内分泌改变可能会影响胎儿的编程，导致成年后出现多种慢性疾病。最近的研究表明，DEHP 及其代谢物单（2-乙基己基）邻苯二甲酸酯（MEHP）的暴露可能会损害胎盘的发育和功能，从而对胎儿的生长产生负面影响。在几种滋养层和胎盘模型中进行的研究表明，DEHP 和 MEHP 对与胎盘发育相关的关键过程有负面影响，如着床、分化、侵袭和血管生成。此外，还报道了许多胎盘功能的改变，如激素信号转导、代谢、营养物质转运、免疫调节和氧化应激反应。此外，临床流行病学证据支持 DEHP 暴露与不良妊娠结局和病理之间的关联。在这篇综述中，我们旨在首次总结 DEHP 和 MEHP 暴露对胎盘发育和病理生理学的影响以及涉及的机制。我们还注意到探索 DEHP 和 MEHP 对不同滋养层细胞群的影响的重要性，并讨论了这个话题的新视角。
