Understanding the role of epigenomic, genomic and genetic alterations in the development of endometriosis (Review)

Abstract

Endometriosis is a complex disease influenced by genetic, epigenetic and environmental factors. The aim of the present study was to describe genomic instability, genetic polymorphisms and their haplotype, epigenetic alterations associated with predisposition to endometriosis, and the key factors associated with endometriosis-related ovarian neoplasms. Focus has been given on the developing paradigm that epigenetic alterations or genetic mutations in endometriosis may start in utero or in adolescent and young adults. A search was conducted between 1966 and 2010 through the English language literature (online Medline PubMed database) using the keywords endometriosis combined with epigenetic, genetic and environment. Genetic/epigenetic alterations include single‑nucleotide polymorphisms (SNPs), copy number variation, loss of heterozygosity (LOH), and promoter methylation. Several genes with genetic polymorphisms analyzed in the present study tended to overlap previously reported endometriosis susceptibility genes. Retrograde menstruation leads to iron overload, which facilitates the accumulation of somatic mutations through Fenton reaction-mediated oxidative stress. The epigenetic disruption of gene expression plays an important role in the development of endometriosis through interaction with environmental changes. There seems to be at least three spatiotemporally distinct phases of the development of endometriosis: the initial phase of genetic background inherited from parents; followed by epigenetic modifications in the female offspring; and iron overload, which is subject to dynamic modulation later in life. In conclusion, the marked regulation of endometriosis susceptibility genes may stem from a mechanism responsible for epigenetic and genetic mutations based on the microenvironmental changes.

Prevalence of high‐risk human papillomavirus infection in women with ovarian endometriosis

“…9,10 It has been suggested that genetic, immunological, or environmental factors might be involved in this process. [10][11][12] Moreover, considering the malignant and immunological processes of the disease, the concept of a possible causal role of infectious agents has developed recently. 13,14 It has been suggested that intrauterine infection could initiate the endometriosis process by activating proinflammatory pathways and innate immunity.…”

Exposure to the environmental endocrine disruptor TCDD and human reproductive dysfunction: Translating lessons from murine models

“…Perhaps predictably, studies have also identified differential methylation/acetylation profiles between the eutopic endometrium and ectopic sites of tissue growth in women with endometriosis (for example, [132–134]). Several functional studies linked altered decidualization capacity in women with endometriosis to abnormal epigenetic marks (ie, [135, 136]). For example, subjecting primary cultures of stromal cells, obtained from women with or without endometriosis, to a standard decidualization protocol, Bulun and colleagues identified a failure of decidualization-associated downregulation of DNMT3B hormones [137].…”

Malignome auf dem Boden einer Endometriose

“…Vielleicht führen die zyklisch wiederkehrenden Blutungen innerhalb der ovariellen Endometriome über eine Eisenüberladung und die Erhöhung von Sauerstoffradikalen zu genetischen Veränderungen [16,20,24]. So könnten durch das veränderte Mikromilieu im Epithel der ovariellen Endometriome somatische Mutationen akkumulieren, die über verschiedene Vorstufen ("atypische Endometriose") zur Entwicklung eines Ovarialkarzinoms führen.…”