Genetika i epigenetika endometrioza

master's thesis

• Title (english): Genetics and epigenetics of endometriosis
• Author: Dora Šimović
• Mentor: Ljiljana Šerman (mentor)
• Committee member: Berivoj Mišković (predsjednik povjerenstva)
• Committee member: Tamara Nikuševa Martić (član povjerenstva)
• Committee member: Ljiljana Šerman (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Medical Biology); Zagreb
• Defense date and country: 2017-07-14, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Human Genetics, Genomics and Proteomics

Abstract

Endometrioza je česta ginekološka bolest koja najčešće zahvaća žene reproduktivne dobi. Definirana je nazočnošću i rastom ektopičnog endometrija koji ima histološke značajke normalnog endometrija. Točna etiologija endometrioze još uvijek nije poznata. Novija istraživanja govore u prilog utjecaju abnormalnih epigenetskih mehanizama na patogenezu endometrioze, poput DNA metilacije, sinteze malih nekodirajućih molekula RNA i modifikacije histona. DNA metilacija je jedna od najčešćih modifikacija DNA i predstavlja kovalentno vezanje metilne skupine na peti ugljikov atom citozinskog prstena na CpG dinukleotidima. Metilacija promotorske regije gena dovodi do utišavanja tog gena. MikroRNA reguliraju posttranskripcijsku gensku ekspresiju vežući se na 3' kraj mRNA regije koja se ne prevodi i dovode do smanjenja sinteze određenog proteina. Postoji barem 8 načina modifikacije histona, ali acetilacija je najviše istraživana. Na „globalnoj“ razini, acetilacija histona je povezana s aktivacijom transkripcije. Uočene su varijacije u epigenetskim uzorcima gena za koje je poznato da sudjeluju u promjenama hormonskog, imunološkog i upalnog stanja endometrioze. Tako je za endometriozu tipična hipometilacija ERβ, gena za aromatazu i SF-1, te hipermetilacija promotorskih regija PR-B, gena koji kodiraju za inhibitore histonskih deacetilaza i DNMT. Usprkos tome, i dalje nije razjašnjeno predstavljaju li te molekularne promjene uzrok ili posljedicu bolesti. Cilj ovog preglednog rada je sustavno predstaviti i analizirati do sada otkrivene epigenetske promjene u endometriozi jer u budućnosti ove promjene mogu predstavljati terapijske ciljeve u obliku farmakoloških lijekova koji mogu modificirati epigenetski kod.

Abstract (english)

Endometriosis is a common gynecological disease which mainly affects women of reproductive age. It is defined by the presence and growth of ectopic endometrial tissue which has the histological characteristics of the normal endometrium. The precise aetiology of endometriosis remains unclear. Accumulating evidence suggests that various epigenetic aberrations may play an essential role in the pathogenesis of endometriosis, such as DNA methylation, synthesis of small non-coding RNA, and histone modification. DNA methylation is one of the most common DNA modification and it represents the covalent bonding of the methyl group to the fifth carbon atom of the cytosine in the CpG dinucleotides. Methylation of the gene promoter region leads to its suppression. MicroRNAs regulate gene expression at the posttranscriptional level by specifically binding to the 3'-untranslational region of targeted mRNA and downregulate the expression of specific proteins. At least eight patterns of histone modification have been identified, with acetylation being the most intensively studied. „Global“ histone acetylation is related to transcriptional activity. Variations in the epigenetic patterns of genes known to be involved in the aberrant hormonal, immunologic, and inflammatory status of endometriosis have been observed. Thus, hypomethylation of ERβ, aromatase gene and SF-1, and hypermethylation of PR-B promoter regions, coding genes for histone deacetylase inhibitors and DNMTs are typical for endometriosis. Nonetheless, it is still unclear whether these molecular changes are the cause or consequence of the disease. The aim of this review is to present an overview and analyze so far known epigenetic alterations in endometriosis because, in the future, this alterations may constitute therapeutic targets for pharmacological compounds able to modify the epigenetic code.

• Keywords: epigenetika; endometrioza; DNA metilacija
• Keywords (english): epigenetics; endometriosis; DNA methylation
• Language: croatian
• URN:NBN: urn:nbn:hr:105:822804
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-11-03 10:09:39