High-fat diet induced obesity alters Dnmt1 and Dnmt3a levels and global DNA methylation in mouse ovary and testis.

Abstract

Obesity impairs reproductive capacity, and the link between imprinting disorders and obesity has been discussed in many studies. Recent studies indicate that a high-fat diet may cause epigenetic changes in maternal and paternal genes, which may be transmitted to offspring and negatively affect their development. On this basis, our study aims to reveal the changes in DNA methylation and DNA methyltransferase enzymes in the ovaries and testes of C57BL/6 mice fed a high-fat diet and created a model of obesity, by comparing them with the control group. For this purpose, we demonstrated the presence and quantitative differences of DNA methyltransferase 1 and DNA methyltransferase 3a enzymes as well as global DNA methylation in ovaries and testis of C57BL/6 mice fed a high-fat diet by using immunohistochemistry and western blot methods. We found that a high-fat diet induces the levels of Dnmt1 and Dnmt3a proteins (p < 0.05). We observed increased global DNA methylation in testes but, interestingly, decreased global DNA methylation in ovaries. We think that our outcomes have significant value to demonstrate the effects of obesity on ovarian follicle development and testicular spermatogenesis and may bring a new perspective to obesity-induced infertility treatments. Additionally, to the best of our knowledge, this is the first study to document dynamic alteration of Dnmt1 and Dnmt3a as well as global DNA methylation patterns during follicle development in healthy mouse ovaries.