背景:尽管医学进步,但妊娠高血压疾病(HDP)仍然是全球重大的健康负担。HDP患病率似乎在上升,导致产妇和胎儿并发症增加,死亡率,和大量的医疗费用。HDP的病因是复杂和多方面的,受营养等因素的影响,肥胖,压力,代谢紊乱,和遗传学。新出现的证据表明环境污染物,特别是全氟烷基和多氟烷基物质(PFAS),可能有助于HDP的发展。
目的:本综述综合流行病学和机制数据,探讨PFAS暴露与HDP之间的复杂关系。
■研究表明,PFAS暴露与HDP之间存在不同程度的关联,有些人表现出正相关,尤其是先兆子痫。荟萃分析提示这些关联中潜在的胎儿性别特异性差异。
■机械,PFAS暴露似乎会破坏血管血流动力学,胎盘发育,以及血管生成和性类固醇调节等关键过程。实验研究揭示了肾素-血管紧张素系统的改变,滋养细胞入侵,氧化应激,炎症,和激素失调-所有这些都有助于HDP的发病机理。阐明这些机制对于制定预防策略至关重要。
■有针对性的干预措施,如AT2R激动剂,caspase抑制剂,和特定microRNA的调节显示出在减轻妊娠期间与PFAS暴露相关的不良结局方面的希望。
■需要进一步的研究来全面了解PFAS诱导的胎盘改变的全谱及其对孕产妇和胎儿健康的长期影响。这些知识将有助于在不断变化的环境景观中为HDP制定有效的预防和治疗策略。
BACKGROUND: Hypertensive disorders of pregnancy (HDP) remain a significant global health burden despite medical advancements. HDP prevalence appears to be rising, leading to increased maternal and fetal complications, mortality, and substantial healthcare costs. The etiology of HDP are complex and multifaceted, influenced by factors like nutrition, obesity, stress, metabolic disorders, and genetics. Emerging evidence suggests environmental pollutants, particularly Per- and polyfluoroalkyl substances (PFAS), may contribute to HDP development.
OBJECTIVE: This review integrates epidemiological and mechanistic data to explore the intricate relationship between PFAS exposure and HDP.
UNASSIGNED: Studies show varying degrees of association between PFAS exposure and HDP, with some demonstrating positive correlations, particularly with preeclampsia. Meta-analyses suggest potential fetal sex-specific differences in these associations.
UNASSIGNED: Mechanistically, PFAS exposure appears to disrupt vascular hemodynamics, placental development, and critical processes like angiogenesis and sex steroid regulation. Experimental studies reveal alterations in the renin-angiotensin system, trophoblast invasion, oxidative stress, inflammation, and hormonal dysregulation - all of which contribute to HDP pathogenesis. Elucidating these mechanisms is crucial for developing preventive strategies.
UNASSIGNED: Targeted interventions such as AT2R agonists, caspase inhibitors, and modulation of specific microRNAs show promise in mitigating adverse outcomes associated with PFAS exposure during pregnancy.
UNASSIGNED: Further research is needed to comprehensively understand the full spectrum of PFAS-induced placental alterations and their long-term implications for maternal and fetal health. This knowledge will be instrumental in developing effective preventive and therapeutic strategies for HDP in a changing environmental landscape.