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Endometriosis: current challenges in modeling a multifactorial disease of unknown etiology.

ABSTRACT: Endometriosis is a chronic inflammatory hormone-dependent condition associated with pelvic pain and infertility, characterized by the growth of ectopic endometrium outside the uterus. Given its still unknown etiology, treatments usually aim at diminishing pain and/or achieving pregnancy. Despite some progress in defining mode-of-action for drug development, the lack of reliable animal models indicates that novel approaches are required. The difficulties inherent to modeling endometriosis are related to its multifactorial nature, a condition that hinders the recreation of its pathology and the identification of clinically relevant metrics to assess drug efficacy. In this review, we report and comment endometriosis models and how they have led to new therapies. We envision a roadmap for endometriosis research, integrating Artificial Intelligence, three-dimensional cultures and organ-on-chip models as ways to achieve better understanding of physiopathological features and better tailored effective treatments.

SUBMITTER: Malvezzi H

PROVIDER: S-EPMC7425005 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Endometriosis: current challenges in modeling a multifactorial disease of unknown etiology.

Malvezzi Helena H Marengo Eliana Blini EB Podgaec Sérgio S Piccinato Carla de Azevedo CA

Journal of translational medicine 20200812 1

Endometriosis is a chronic inflammatory hormone-dependent condition associated with pelvic pain and infertility, characterized by the growth of ectopic endometrium outside the uterus. Given its still unknown etiology, treatments usually aim at diminishing pain and/or achieving pregnancy. Despite some progress in defining mode-of-action for drug development, the lack of reliable animal models indicates that novel approaches are required. The difficulties inherent to modeling endometriosis are rel ...[more]

PMID: 32787880

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Project description:The prevalence of gastric cancer is associated with several factors including geographical location, diet, and genetic background of the host. However, it is evident that infection with Helicobacter pylori (H. pylori) is crucial for the development of the disease. Virulence of the bacteria is also important in modulating the risk of the disease. After infection, H. pylori gains access to the gastric mucosa and triggers the production of cytokines that promote recruitment of inflammatory cells, probably involved in tissue damage. Once the infection is established, a cascade of inflammatory steps associated with changes in the gastric epithelia that may lead to cancer is triggered. H. pylori-induced gastritis and H. pylori-associated gastric cancer have been the focus of extensive research aiming to discover the underlying mechanisms of gastric tissue damage. This research has led to the association of host genetic components with the risk of the disease. Among these is the presence of single nucleotide polymorphisms (SNPs) in several genes, including cytokine genes, which are able to differentially modulate the production of inflammatory cytokines and then modulate the risk of gastric cancer. Interestingly, the frequency of some of these SNPs is different among populations and may serve as a predictive factor for gastric cancer risk within that specific population. However, the role played by other genetic modifications should not be minimized. Methylation of gene promoters has been recognized as a major mechanism of gene expression regulation without changing the primary structure of the DNA. Most DNA methylation occurs in cytosine residues in CpG dinucleotide, but it can also be found in other DNA bases. DNA methyltransferases add methyl groups to the CpG dinucleotide, and when this methylation level is too high, the gene expression is turned off. In H. pylori infection as well as in gastric cancer, hypermethylation of promoters of genes involved in cell cycle control, metabolism of essential nutrients, and production of inflammatory mediators, among others, has been described. Interestingly, DNA changes like SNPs or mutations can create CpG sites in sequences where transcription factors normally sit, affecting transcription.In this chapter, we review the literature about the role of SNPs and methylation on H. pylori infection and gastric cancer, with big emphasis to the H. pylori role in the development of the disease due to the strong association between both.

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Endometriosis: current challenges in modeling a multifactorial disease of unknown etiology.

Publications

Endometriosis: current challenges in modeling a multifactorial disease of unknown etiology.

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