The "epigenetic landscape" hypothesis implicated in development of major obstetric conditions, such as endometriosis, uterine leiomyoma, and preeclampsia

Abstract

Human genome mapping supplemented with novel molecular technologies has significantly contributed to our insight into pathogenomic mechanisms of common disorders and thus gave birth to molecular (genomic) medicine based on a complex approach to studying normal and abnormal development. Endometriosis (EM), uterine leiomyoma (ULM), and preeclampsia (PE) as three major obstetrical disorders are good examples of common diseases (CD) that have been thoroughly studied in our laboratory as well as in many obstetric centers throughout the world. The systemic genetic approach used in such studies includes identification of causative genes and relevant gene networks, discovering peculiarities of affected metabolic methylation pathways, and profiling the gene expression supplemented with the next generation sequencing. Reviewing the available data leaves little doubt that both EM and ULM are syntropic (genetically related) diseases sharing in common many molecular features. Meanwhile, the existence of numerous clinical forms for EM, ULM, and PE suggests a major role of epigenetic landscape in their development. According to the reviewed data, each CD should be treated not as a single unit but as a bulk of clinically close entities with their own genetic and epigenetic backgrounds attributed to the unique pattern of causative genes as well as to peculiarities of their epigenetic regulation occurring against a unique, personal genetic background. Once started, pathological progression soon becomes irreversible at a certain point of no-return, after which the pathological process becomes canalized and produces some or another specific clinical form of a particular CD. The "epigenetic landscape" hypothesis seems to be applicable to development of many, if not all, CDs. Creation of huge biobanks with abundant collections of samples from different clinical forms of a particular CD and whole-genome sequencing of relevant DNA samples accompanied by bioinformatics interpretation should be used to get more insight into different CD clinical forms.