The Effects Of Alcohol On Germ Cells And Epigenetic Modifications Of Preimplantation Embryos In Mouse

Previous studies have shown that parents with alcohol drinking during pregnancy could cause birth defects in offspring, such as the patients’ face distorting, the central nervous system with imperfect development, memory capacity significantly decreasing and communication skills lacking after their adulthood, which is called fetal alcohol syndrome disorders(FASD) in medicine. Recently, alcohol’s effect on genetic modification, causing pathogenesis of this disease, has become a hot spot. The research of its pathogenesis focused on nervous system development in this field. It is well-known that establishing an order epigenetic pattern of pre-implantation embryos is essential for fetal development. Disorder epigenetic patterns of pre-implantation embryos would cause abnormal fetal development and adult diseases. Our previous works have found that epigenetic modifications of pre-implantation embryos are susceptible to environmental factors. Changes in the environment could cause disorder of epigenetic patterns. Therefore, we speculate that alcohol might influence epigenetic modifications in the early embryos.Epigenetic modifications, including DNA methylation, histone modifications, and noncoding RNAs, have generally been recognized as important factors by regulating gene expression at every step of transitions for cell fate and development of embryo. Especially, DNA methylation could serve as important epigenetic modifications. Alcohol ingestion in animals has been shown to interfere with the synthesis and metabolism of methionine, thereby disrupting important methylation procession mediated by S-Adenosylmethionine. An increasing number of researches have been showed that DNA methylation profiles of all kinds of tissues were altered by alcohol consumption. So we guess alcohol may influence pre-implantation DNA methylation levels. The amino-terminal histone modification is an important epigenetic mechanism, a direct impact on the structure of chromosomes which could regulate gene expression. Histone methylation and acetylation play an important role in the regulation of gene expression and affect the basic developmental processes of organisms. In the paternal or maternal alcohol exposure during pregnancy, parents with alcohol intake during pregnancy may damage DNA methylation and histone modifications of pre-implantation embryo. We provide prevent the harm of alcohol to the fetus. The mice are commonly used as a model for this disease. In order to study the pathogenesis involved about epigenetic of FASD and provide experimental evidence for the treatment of the disease, this study use gavage method in vivo, HE staining, sperm quality analysis techniques, technology of embryos obtained in vivo, embryo culture and immunofluorescence techniques to analysis alcohol’effects on the liver and semen quality, germ cells and histone modifications of embryos in vivo and in vitro. Males, females and males or females before and after pregnancy were treated with chronic alcohol consumption. The impacts of alcohol on germ cells and global DNA methylation level of pre-implantation embryonic were analysised. We further investigated effects of alcohol on H3K27trimethylation/acetylation patterns about females pregnant in the later period. Experimental data show germ cells and pre-implantation embryos of mice with alcohol treatment abnormal cause genetic modifications. The results are as follows:males with alcohol treatment could cause some damage in liver, semen quality and decreasing DNA methylation of sperms. Decreasing DNA methylation of sperms could cause abnormal global DNA methylation in pre-implantation embryos. As for females with chronic alcohol ingestion, DNA methylation levels of germ cells and embryos were significantly lower than the control group. In attempt to explain the extent of damage in single parent or parents with parental alcoholism differences, we conducted four experiments. DNA methylation level of four experiments was detected and the results show parents with alcoholism were the largest damage to pre-implantation embryos. Females with chronic alcohol were larger than males. As for females with chronic alcohol ingestion, experiments show the effects of alcohol on H3K27trimethylation in preimplantation embryo is not obvious, however, experiments in vitro and in vivo, suggest that alcohol has a great effect on embryonic H3K27acetylation levels.We found that the mice with alcohol ingestion during pregnancy can disorder epigenetic modifications of pre-implantation embryos to reveal the pathogenesis of fetal alcohol syndrome, which provides important lessons. For an in-depth understanding of the harm of alcohol exposure during pregnancy, this research provide experimental basis for a long period of time to influence offspring and a way to prevent the damage to PAE offspring.