Endocrine Disruptors, Epigenetic Changes, and Transgenerational Transmission

Recent discoveries in the field of molecular biology are focused on phenomena like chromatin condensation, histone (H) modification, and deoxyribonucleic acid (DNA) methylation, as well as the action of small non-coding ribonucleic acid (RNA), which together belong to the branch of epigenetics. The term “epigenetics” was coined in 1940 by Conrad Waddington [1] who described it as “the branch of biology which studies the causal interactions between genes and their product which bring phenotypes into being.” In fact, epigenetics includes all those mechanisms that are able to regulate DNA expression without modifying nucleotide sequence. Among the main epigenetic mechanisms mentioned earlier, DNA methylation is the most widely known and most studied modification (Table 3.1). The process of DNA methylation constitutes a postreplicative modification, in which a methyl group is added covalently to a DNA residue [10]. The methylation occurs at the carbon 5 of the cytosine ring in 5′-3′-oriented CG dinucleotides (named as CpGs), and it is catalyzed by the action of DNA methyltransferases (DNMTs)[11]. Furthermore, recent evidences have shown that also RNA factors, such as small RNAs (small interfering RNA [siRNA] and microRNA [miRNA]), have the ability to direct DNA methylation through a mechanism called RNA-directed DNA methylation (RdDM), performed by double-stranded RNA (dsRNA), which may be produced after the transcription of inverted repeats [12].