Dangudubiyyam Sri Vidya, Hofmann Alissa, Yadav Pankaj, Kumar Sathish
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA; Endocrinology-Reproductive Physiology Program, University of Wisconsin, Madison, WI 53715, USA.
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA.
Reprod Toxicol. 2024 Dec;130:108702. doi: 10.1016/j.reprotox.2024.108702. Epub 2024 Aug 31.
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.
This review integrates epidemiological and mechanistic data to explore the intricate relationship between PFAS exposure and HDP.
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.
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.
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.
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.
尽管医学不断进步，但妊娠期高血压疾病（HDP）仍然是一项重大的全球健康负担。HDP的患病率似乎在上升，导致孕产妇和胎儿并发症增加、死亡率上升以及大量医疗费用。HDP的病因复杂且多方面，受营养、肥胖、压力、代谢紊乱和遗传等因素影响。新出现的证据表明，环境污染物，特别是全氟和多氟烷基物质（PFAS），可能导致HDP的发生。
本综述整合了流行病学和机制数据，以探讨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，一些研究显示出正相关，特别是与子痫前期。荟萃分析表明这些关联可能存在胎儿性别特异性差异。
从机制上讲，PFAS暴露似乎会扰乱血管血流动力学、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、滋养层细胞侵袭、氧化应激、炎症和激素失调的改变——所有这些都有助于HDP的发病机制。阐明这些机制对于制定预防策略至关重要。
靶向干预措施，如AT2R激动剂、半胱天冬酶抑制剂和特定微小RNA的调节，在减轻孕期PFAS暴露相关的不良后果方面显示出前景。
需要进一步研究以全面了解PFAS引起的胎盘改变的全貌及其对母婴健康的长期影响。这些知识将有助于在不断变化的环境中为HDP制定有效的预防和治疗策略。
