[Studies on molecular teratogenic mechanism of methylmercury in early developing rat embryos].
The present study further revealed the teratogenic mechanism of methylmercury chloride (MMC) during rat neurulation by means of nonradioactive in situ hybridization (ISH), semiquantitative analysis of immunohistochemical staining and in vivo teratogenic test. The main aim was to teat the hypothesis that iNOS, HSP70, NT, TGF-beta and Bcl-2 genes contribute to MMC-induced day 9.5 embryonic damages. Results showed there were no obvious poisoning signs and death of pregnant female rats injected intraperitoncally with 0, 0.2, 0.4, 0.8, 1.6 and 3.2 mg/kg MMC. While the doses increased, the total morphological scores decreased gradually, and the rates of embryo deformity and development delay increased step by step to 34% and 76% respectively. The levels of iNOS mRNA and protein and HSP70 mRNA increased, and NT mRNA with its protein became down, all these changes were concentration dependent. In addition, MMC could inhibit the level of TGF-beta mRNA, but no obvious influence on the levels of Bcl-2 mRNA and Bcl-2 protein. On the basis of parallel findings from embryos, genes and proteins, abnormal expression of genes in transcriptional level might be related to MMC-induced teratogenic insult.
Li
Y
Y
National Center for Maternal and Infant Health, Beijing Medical University, Beijing 100083, China.
Zhang
T
T
Wang
L
L
Li
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Z
D000818:Animals; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D011134:Polysaccharides / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013723:Teratogens / Q000633:toxicity*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics
D006133:Growth Substances; D018840:HSP70 Heat-Shock Proteins; D008767:Methylmercury Compounds; D011134:Polysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D013723:Teratogens; D016212:Transforming Growth Factor beta; C010491:neurotropin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004925:methylmercuric chloride