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器官发生期间二甲苯暴露对胎-胎盘效率和胎儿活力的影响:探讨其与氧化应激诱导的炎症和细胞凋亡的关系。

Impact of xylene exposure during organogenesis on foeto-placental efficiency and foetal viability: Exploring its association with oxidative stress-induced inflammation and apoptosis .

机构信息

Department of Anatomy, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.

Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.

出版信息

Toxicol Ind Health. 2024 Dec;40(12):692-710. doi: 10.1177/07482337241286569. Epub 2024 Sep 23.

DOI:10.1177/07482337241286569
PMID:39308155
Abstract

The potential maternal and foetal toxicity resulting from exposure to xylene at or below the allowable limit of 100 ppm during gestation is not thoroughly studied. The aim of this study was to investigate maternal and foetal outcomes following prenatal exposure to xylene during organogenesis. Pregnant Sprague Dawley (SD) rats were administered intraperitoneal (IP) corn oil (vehicle), 100, 500, and 1000 parts per million (ppm) of xylene from gestational day (GD) 6 until GD17. Clinical signs, maternal weight gain, and food consumption were recorded daily. A caesarean hysterectomy was performed on GD21 to assess the reproductive and foetal outcomes. Exposure to 1000 ppm of xylene caused a significant decrease in the maternal body weight and food consumption, and an increase in intrauterine foetal deaths. Foetal assessment revealed a significant decrease in foetal weight in both male and female foetuses of female rats treated with 500 and 1000 ppm. Male placental weight was significantly decreased in all xylene-treated groups, while 1000 ppm xylene significantly decreased female placental weight. Histologically, marked uterine inflammatory lesions, fibrosis of the liver and renal tissues, as well as increased placental glycogen content were observed. Immunohistochemistry revealed a significant increase in lipid peroxidation and apoptotic markers. Thus, the foeto-maternal toxicities of xylene have been shown to be mediated by a systemic inflammatory response that exacerbates intrauterine oxidative stress and impairs foeto-placental transfer, leading to an increase in foetal mortality.

摘要

在妊娠期间,暴露于二甲苯的潜在母体和胎儿毒性,即使在允许的 100ppm 以下,也尚未得到充分研究。本研究旨在探讨在器官发生期间,孕妇接触二甲苯对母婴结局的影响。将怀孕的 Sprague Dawley(SD)大鼠经腹腔(IP)给予玉米油(对照物)、100ppm、500ppm 和 1000ppm 的二甲苯,从妊娠第 6 天(GD)持续至妊娠第 17 天(GD)。每天记录临床症状、母体体重增加和食物消耗情况。在 GD21 进行剖宫产子宫切除术,以评估生殖和胎儿结局。暴露于 1000ppm 的二甲苯会导致母体体重和食物消耗显著下降,并增加宫内胎儿死亡。胎儿评估显示,暴露于 500ppm 和 1000ppm 二甲苯的雌性大鼠的雄性和雌性胎儿的胎儿体重均显著下降。雄性胎盘的重量在所有二甲苯处理组中均显著降低,而 1000ppm 二甲苯则显著降低了雌性胎盘的重量。组织学上,观察到明显的子宫炎症病变、肝脏和肾脏组织纤维化,以及胎盘糖原含量增加。免疫组织化学显示脂质过氧化和凋亡标志物显著增加。因此,二甲苯的胎母毒性已被证明是由全身炎症反应介导的,这种反应加剧了宫内氧化应激,损害了胎胎胎盘转移,导致胎儿死亡率增加。

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