Laboratorio de Investigación Clínica, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas S/N Ciudad Universitaria Sur, col. La Haciendita, Chilpancingo, Guerrero ZC 39087, Mexico.
Facultad de Bioanálisis, Universidad Veracruzana. Odontólogos W/N, U.H. del Bosque, Xalapa, Veracruz, Mexico.
Toxicol In Vitro. 2018 Aug;50:328-335. doi: 10.1016/j.tiv.2018.04.006. Epub 2018 Apr 17.
Contaminated water with chlorates is a public health problem associated with iodine deficiency. Epidemiological evidence shows that iodine deficiency is a risk factor for preeclampsia (PE). In this study we use human BeWo trophoblast cells exposed to perchlorate (KClO) and changes in gene expression were analyzed by microarrays, quantitative RT-PCR (qRT-PCR) and immunoblot. The microarray analysis identified 48 transcripts up-regulated and 112 down-regulated in comparison with non-exposed trophoblast. The qRT-PCR analysis confirmed changes in GAS7, PKP2, Emilin, Dynatic 3, protocadherins 11, 15, gamma A12, EGFR, SAFB1, ACE2, ANXA2, Apoliprotein E, SREBF1, and C/EBP-β. KClO exposition decreased the mRNA and protein of C/EBP-β and GPX4. Also, we observed a nuclear translocation of HIF1α protein, and increase in both Snail and ACE2 protein by immunoblot. These effects were accompanied by an increases in ROS and nitric oxide. In conclusion, our results show that exposure to KClO alters genes involved in migration, adhesion, differentiation, and correlate with the increase of oxidative stress and nitric oxide production in trophoblast cells. It is possible that iodine deficiency is associated with these processes. However, further studies are required to corroborate the role of iodine in trophoblast cells.
被氯酸盐污染的水是与碘缺乏有关的公共卫生问题。流行病学证据表明，碘缺乏是子痫前期（PE）的一个风险因素。在这项研究中，我们使用人绒毛膜滋养层细胞（BeWo）暴露于高氯酸盐（KClO），通过微阵列、定量 RT-PCR（qRT-PCR）和免疫印迹分析基因表达的变化。与未暴露的滋养层相比，微阵列分析确定了 48 个转录物上调和 112 个转录物下调。qRT-PCR 分析证实 GAS7、PKP2、Emilin、Dynatic 3、原钙黏蛋白 11、15、γA12、EGFR、SAFB1、ACE2、ANXA2、载脂蛋白 E、SREBF1 和 C/EBP-β 的变化。KClO 暴露降低了 C/EBP-β 和 GPX4 的 mRNA 和蛋白水平。此外，我们通过免疫印迹观察到 HIF1α 蛋白的核转位，以及 Snail 和 ACE2 蛋白的增加。这些效应伴随着 ROS 和一氧化氮的产生增加。总之，我们的结果表明，暴露于 KClO 会改变参与迁移、粘附、分化的基因，并与滋养层细胞中氧化应激和一氧化氮产生的增加相关。碘缺乏可能与这些过程有关。然而，需要进一步的研究来证实碘在滋养层细胞中的作用。
