Altered DNA methylation and Dnmt expression in obese uterus may cause implantation failure

Abstract

Abstract Obesity is defined by increased adipose tissue volume and has become a major risk factor for reproduction. Recent studies have revealed a substantial link between obesity and epigenetics. Epigenome is dynamically regulated mainly by DNA methylation. DNA methylation, which is controlled by DNA methyltransferases (Dnmts), has been widely investigated since it is essential for imprinting and regulation of gene expression. In our previous study we showed that level of Dnmt1, Dnmt3a and global DNA methylation was dramatically altered in testis and ovary of high-fat diet (HFD)-induced obese mice. However, it has not yet been demonstrated that effect of HFD on Dnmts and global DNA methylation in mice uterus. Therefore, in the present study, we aimed to evaluate the impact of HFD on the level of Dnmt1, Dnmt3a, Dnmt3b, Dnmt3l and global DNA methylation in uterus. Our results showed that HFD significantly altered levels of Dnmts and global DNA methylation in the uterus. Total expression of Dnmt1, Dnmt3a and Dnmt3b significantly upregulated while level of Dnmt3l and global DNA methylation dramatically decreased (p < 0.05). Furthermore, we observed that expression of Dnmt3b and Dnmt3l significantly increased in endometrium including gland and epithelium (p < 0.05). Although Dnmt3b was the only protein whose expression significantly increased, level of global DNA methylation and Dnmt3l remarkably decreased in stroma and myometrium (p < 0.05). In conclusion, for the first time, our results show that obesity dramatically changes global DNA methylation and expression of Dnmts, and decreased DNA methylation and Dnmt expression may cause abnormal gene expression, especially in the endometrium.