Rani Balu Usha, Vasantharekha Ramasamy, Santosh Winkins, Swarnalingam Thangavelu, Barathi Seetharaman
Endocrine Disruption and Reproductive Toxicology Laboratory (EDART), Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, India.
Toxicology Research on Endocrine Disruptors (TRENDS) Laboratory, PG & Research Department of Advanced Zoology and Biotechnology, Government Arts College, Nandanam, Chennai 600035, India.
Cells. 2025 Mar 26;14(7):493. doi: 10.3390/cells14070493.
Preeclampsia (PE) is a critical complication of pregnancy that affects 3% to 5% of all pregnancies and has been linked to aberrant placentation, causing severe maternal and fetal illness and death.
This systematic review aims to elucidate the association of in-utero endocrine-disrupting chemical (EDC) exposure and microRNAs and their imprinted genes from prenatal and maternal circulation of PE patients.
Databases such as PubMed, PubMed Central, ScienceDirect, the Comparative Toxicogenomics Database (CTD), ProQuest, EBSCOhost, and Google Scholar were utilized to search for articles that investigate the relationships between selected EDCs and epigenetic events such as DNA methylation and microRNAs that are associated with PE.
A total of 29 studies were included in the database search. Altered expression of microRNAs (miR-15a-5p, miR-142-3p, and miR-185) in the placenta of PE patients was positively associated with the urinary concentration of phthalates and phenols in the development of the disease in the first trimester. EDCs such as phenols, phthalates, perfluoroalkyl substances (PFOAs), polybrominated diphenyl ethers (PBDEs), and organochlorine phosphates (OCPs) have been reported to be associated with hypertensive disorders in pregnancy. miRNA-31, miRNA-144, miRNA-145, miRNA-210, placental specific clusters (C14MC, and C19MC) may be used as possible targets for PE because of their potential roles in the onset and progression of PE.
Prenatal EDC exposure, including exposure to BPA, showed association with signaling pathways including estrogen, sFlt-1/PlGF, ErbB, MAPK/ERK, and cholesterol mechanisms with placental hemodynamics. Even low EDC exposures leave altered epigenetic marks throughout gestation, which might cause PE complications.
子痫前期（PE）是一种严重的妊娠并发症，影响3%至5%的妊娠，与胎盘形成异常有关，可导致严重的母婴疾病和死亡。
本系统评价旨在阐明子宫内接触内分泌干扰化学物（EDC）与子痫前期患者产前及母体循环中的微小RNA及其印记基因之间的关联。
利用PubMed、PubMed Central、ScienceDirect、比较毒理基因组学数据库（CTD）、ProQuest、EBSCOhost和谷歌学术等数据库搜索研究选定的EDC与DNA甲基化和微小RNA等与子痫前期相关的表观遗传事件之间关系的文章。
数据库搜索共纳入29项研究。子痫前期患者胎盘中微小RNA（miR-15a-5p、miR-142-3p和miR-185）表达的改变与孕早期疾病发展过程中邻苯二甲酸盐和酚类的尿浓度呈正相关。酚类、邻苯二甲酸盐、全氟烷基物质（PFOA）、多溴二苯醚（PBDE）和有机氯磷酸盐（OCP）等EDC已被报道与妊娠期高血压疾病有关。miRNA-31、miRNA-144、miRNA-145、miRNA-210、胎盘特异性簇（C14MC和C19MC）可能因其在子痫前期发病和进展中的潜在作用而成为子痫前期的可能靶点。
产前接触EDC，包括双酚A，与包括雌激素、sFlt-1/PlGF、ErbB、MAPK/ERK和胆固醇机制在内的信号通路以及胎盘血流动力学有关。即使是低剂量的EDC暴露也会在整个妊娠期留下改变的表观遗传标记，这可能导致子痫前期并发症。
