Epigenetics in reproduction and development

This review article brings a contemporary view on epigenetics in mammalian reproduction and development. The basic epigenetic mechanisms such as DNA methylation, posttranslational histone modifi cations and noncoding RNA, without involving the nucleotide sequence of DNA molecule, regulate gene expression and thus cell proliferation, diff erentiation, dediff erentiation and tumorigenesis. Epigenetic drugs and immature embryonic cells have just been introduced in novel therapeutic strategies of human medicine. As epigenetic mechanisms are involved in the mammalian gamete and embryonic development, the experimental animal models described are of highly relevant for monitoring epigenetic changes, in DNA methylation in particular, and their impact on the off spring. Unfavorable environmental eff ects (e.g., maternal malnutrition) may cause phenotype changes in the next few generations, which are transmitted via transgenerational (or intergenerational) epigenetic eff ects, and some of them by yet unknown mechanisms; they seem to be transmitted via gamete to F3 generation that has never been exposed to the noxious agent (e.g., vinclozolin). The new concept of the developmental origin of health and disease points to epigenetic disorder in the development of obesity and type 2 diabetes in man (e.g., due to maternal malnutrition during gestation), currently referred to as a “thrifty epigenotype”. The harmful environmental factors appear to modify human epigenome, thus specifi c epigenetic modifi cations may serve as exposure markers. The issue of epigenotype heredity and its real role in disease development in the next generations is quite intriguing and important, thus being in the focus of interdisciplinary research.

Read more