Institut de Recerca Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain; BCNatal, Barcelona Center for Maternal-Fetal and Neonatal Medicine, Hospital Sant Joan de Déu and Hospital Clínic, Universitat de Barcelona, 08950 Barcelona, Spain.
Grup de Recerca Infancia i Entorn (GRIE), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain; Faculty of Health Sciences, Valencian International University (VIU), 46002, Valencia, Spain.
Sci Total Environ. 2024 Nov 10;950:175080. doi: 10.1016/j.scitotenv.2024.175080. Epub 2024 Jul 28.
The ubiquitous presence of phthalate compounds in cosmetics, personal care products and plastics commonly used in toys, food packaging or household products, results in human exposure with adverse effects on reproductive health and fetal development. Following the PRISMA methodology, this systematic review analyzes the effect of prenatal phthalate exposure on major pregnancy complications, such as gestational diabetes, pregnancy-induced hypertension, fetal growth restriction and preterm birth, and its role in fetal neurodevelopment. This review includes >100 articles published in the last 10 years, showing an association between maternal exposure to phthalates and the risk of developing pregnancy complications. Phthalates are negatively associated with motor skills and memory, and also increase the risk of delayed language acquisition, autism spectrum disorder traits, and behavioral deficits, such as attention deficit hyperactivity disorder in children prenatally exposed to phthalates. Di (2-ethylhexyl) phthalate and its metabolites (mono(2-ethylhexyl) phthalate, mono(3-carboxypropyl) phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate) are the main compounds associated with the above-mentioned pregnancy complications and fetal neurodevelopmental disorders. In addition, this review discusses the molecular mechanisms responsible for various pregnancy complications and neurodevelopmental disorders, and the critical window of exposure, in order to clarify these aspects. Globally, the most common molecular mechanisms involved in the effects of phthalates are endocrine disruption, oxidative stress induction, intrauterine inflammation, and DNA methylation disorders. In general, the critical window of exposure varies depending on the pathophysiology of the complication being studied, although the first trimester is considered an important period because some of the most vulnerable processes (embryogenesis and placentation) begin early in pregnancy. Future research should aim to understand the specific mechanism of the disruptive effect of each component and to establish the toxic dose of phthalates, as well as to elucidate the most critical period of pregnancy for exposure and the long-term consequences for human health.
邻苯二甲酸酯化合物普遍存在于化妆品、个人护理产品和玩具、食品包装或家用产品中常用的塑料中，这导致人类接触这些化合物，对生殖健康和胎儿发育产生不良影响。本系统综述按照 PRISMA 方法，分析了产前邻苯二甲酸酯暴露对主要妊娠并发症（如妊娠期糖尿病、妊娠高血压、胎儿生长受限和早产）的影响及其对胎儿神经发育的作用。本综述包括过去 10 年发表的 100 多篇文章，表明母体接触邻苯二甲酸酯与发生妊娠并发症的风险之间存在关联。邻苯二甲酸酯与运动技能和记忆力呈负相关，也会增加儿童语言发育迟缓、自闭症谱系障碍特征和行为缺陷（如注意力缺陷多动障碍）的风险，这些儿童在产前接触邻苯二甲酸酯。邻苯二甲酸二（2-乙基己基）酯及其代谢物（单（2-乙基己基）邻苯二甲酸酯、单（3-羧基丙基）邻苯二甲酸酯、单（2-乙基-5-羟基己基）邻苯二甲酸酯、单（2-乙基-5-氧代己基）邻苯二甲酸酯）是与上述妊娠并发症和胎儿神经发育障碍相关的主要化合物。此外，本综述还讨论了导致各种妊娠并发症和神经发育障碍的分子机制以及暴露的关键窗口期，以阐明这些方面。在全球范围内，涉及邻苯二甲酸酯作用的最常见分子机制是内分泌干扰、氧化应激诱导、宫内炎症和 DNA 甲基化紊乱。一般来说，暴露的关键窗口期取决于所研究并发症的病理生理学，尽管孕早期被认为是一个重要时期，因为一些最脆弱的过程（胚胎发生和胎盘形成）在怀孕早期就开始了。未来的研究应旨在了解每种成分的破坏性影响的具体机制，并确定邻苯二甲酸酯的毒性剂量，以及阐明妊娠期间暴露的最关键时期和对人类健康的长期后果。
