Kowalski Thayne Woycinck, Gomes Julia do Amaral, Feira Mariléa Furtado, Dupont Ágata de Vargas, Recamonde-Mendoza Mariana, Vianna Fernanda Sales Luiz
Postgraduation Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
Laboratory of Immunobiology and Immunogenetics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
Front Neurosci. 2020 Nov 25;14:591196. doi: 10.3389/fnins.2020.591196. eCollection 2020.
Embryofetal development is a critical process that needs a strict epigenetic control, however, perturbations in this balance might lead to the occurrence of congenital anomalies. It is known that anticonvulsants potentially affect epigenetics-related genes, however, it is not comprehended whether this unbalance could explain the anticonvulsants-induced fetal syndromes. In the present study, we aimed to evaluate the expression of epigenetics-related genes in valproic acid, carbamazepine, or phenytoin exposure. We selected these three anticonvulsants exposure assays, which used murine or human embryonic stem-cells and were publicly available in genomic databases. We performed a differential gene expression (DGE) and weighted gene co-expression network analysis (WGCNA), focusing on epigenetics-related genes. Few epigenetics genes were differentially expressed in the anticonvulsants' exposure, however, the WGCNA strategy demonstrated a high enrichment of chromatin remodeling genes for the three drugs. We also identified an association of 46 genes related to Fetal Valproate Syndrome, containing and , and nine genes to Fetal Hydantoin Syndrome, including , and . The evaluation of stem-cells under drug exposure can bring many insights to understand the drug-induced damage to the embryofetal development. The candidate genes here presented are potential biomarkers that could help in future strategies for the prevention of congenital anomalies.
胚胎发育是一个需要严格表观遗传控制的关键过程，然而，这种平衡的扰动可能导致先天性异常的发生。已知抗惊厥药可能影响与表观遗传学相关的基因，然而，这种失衡是否能解释抗惊厥药诱导的胎儿综合征尚不清楚。在本研究中，我们旨在评估丙戊酸、卡马西平或苯妥英暴露后与表观遗传学相关基因的表达。我们选择了这三种抗惊厥药暴露试验，这些试验使用了小鼠或人类胚胎干细胞，并且在基因组数据库中公开可用。我们进行了差异基因表达（DGE）和加权基因共表达网络分析（WGCNA），重点关注与表观遗传学相关的基因。在抗惊厥药暴露中，很少有表观遗传学基因差异表达，然而，WGCNA策略显示这三种药物的染色质重塑基因高度富集。我们还确定了46个与胎儿丙戊酸综合征相关的基因，包括 和 ，以及9个与胎儿乙内酰脲综合征相关的基因，包括 和 。药物暴露下干细胞的评估可以为理解药物对胚胎发育的损伤带来许多见解。这里提出的候选基因是潜在的生物标志物，有助于未来预防先天性异常的策略。
