Computational insights into maternal environmental pollutants and folate pathway regulation

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY Reproductive toxicology Pub Date : 2024-12-26 DOI:10.1016/j.reprotox.2024.108825

Adarsh Kumar Shukla, Shadab Ahamad, Prachi Kukshal

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Abstract

Exposure to environmental pollutants during pregnancy can adversely affect fetal growth and postnatal development. While numerous studies have explored the interaction between environmental toxic chemicals and the folate pathway, few have examined their inhibitory effects on key targets. This computational study identified 27 maternal environmental toxicants using the Comparative Toxicogenomics Database (CTD) and analyzed them to identify their targets. Molecular modeling, docking, and dynamics simulations revealed that folate receptors (FOLR1, FOLR2, and FOLR3) and transporters (SLC19A1 and SLC46) are major targets. Among these, FOLR3 exhibited the strongest interactions with toxicants such as Dichlorodiphenyltrichloroethane (DDT), Bisphenols, Dioxin, and other investigated toxicants. Toxicity profiling showed that even minimal exposure to these pollutants significantly impacts maternal health and disrupts folate metabolism, leading to fetal malformations. This study highlights the critical role of maternal toxicants in hindering the folate pathway, with severe implications for fetal development.

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计算洞察母体环境污染物和叶酸途径调节。

怀孕期间暴露于环境污染物会对胎儿生长和产后发育产生不利影响。虽然许多研究已经探索了环境有毒化学物质与叶酸途径之间的相互作用，但很少有人研究它们对关键靶点的抑制作用。本计算研究使用比较毒物基因组数据库（CTD）确定了27种母体环境毒物，并对其进行分析以确定其目标。分子模型、对接和动力学模拟显示叶酸受体（FOLR1、FOLR2和FOLR3）和转运体（SLC19A1和SLC46）是主要靶点。其中，FOLR3与二氯二苯三氯乙烷（DDT）、双酚类、二恶英和其他研究毒物的相互作用最强。毒性分析表明，即使最低限度地接触这些污染物也会严重影响孕产妇健康，破坏叶酸代谢，导致胎儿畸形。这项研究强调了母体有毒物质在阻碍叶酸通路中的关键作用，对胎儿发育有严重影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Reproductive toxicology 生物-毒理学

CiteScore

6.50

自引率

3.00%

发文量

131

审稿时长

45 days

期刊介绍： Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine. All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.