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doctoral thesis
Metilacija RB1 i H19 gena te LINE 1 ponavljajućih sljedova tijekom fetalnog razvoja sjemenika u čovjeka i u štakora
Zagreb: University of Zagreb, School of Medicine, 2022. urn:nbn:hr:105:820020
Himelreich Perić, Marta
University of Zagreb
School of Medicine

Institutional repository: Dr Med - University of Zagreb School of Medicine Digital Repository

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Himelreich Perić, M. (2022). Metilacija RB1 i H19 gena te LINE 1 ponavljajućih sljedova tijekom fetalnog razvoja sjemenika u čovjeka i u štakora (Doctoral thesis). Zagreb: University of Zagreb, School of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:105:820020

Himelreich Perić, Marta. "Metilacija RB1 i H19 gena te LINE 1 ponavljajućih sljedova tijekom fetalnog razvoja sjemenika u čovjeka i u štakora." Doctoral thesis, University of Zagreb, School of Medicine, 2022. https://urn.nsk.hr/urn:nbn:hr:105:820020

Himelreich Perić, Marta. "Metilacija RB1 i H19 gena te LINE 1 ponavljajućih sljedova tijekom fetalnog razvoja sjemenika u čovjeka i u štakora." Doctoral thesis, University of Zagreb, School of Medicine, 2022. https://urn.nsk.hr/urn:nbn:hr:105:820020

Himelreich Perić, M. (2022). 'Metilacija RB1 i H19 gena te LINE 1 ponavljajućih sljedova tijekom fetalnog razvoja sjemenika u čovjeka i u štakora', Doctoral thesis, University of Zagreb, School of Medicine, accessed 23 December 2024, https://urn.nsk.hr/urn:nbn:hr:105:820020

Himelreich Perić M. Metilacija RB1 i H19 gena te LINE 1 ponavljajućih sljedova tijekom fetalnog razvoja sjemenika u čovjeka i u štakora [Doctoral thesis]. Zagreb: University of Zagreb, School of Medicine; 2022 [cited 2024 December 23] Available at: https://urn.nsk.hr/urn:nbn:hr:105:820020

M. Himelreich Perić, "Metilacija RB1 i H19 gena te LINE 1 ponavljajućih sljedova tijekom fetalnog razvoja sjemenika u čovjeka i u štakora", Doctoral thesis, University of Zagreb, School of Medicine, Zagreb, 2022. Available at: https://urn.nsk.hr/urn:nbn:hr:105:820020

Metadata
TitleMetilacija RB1 i H19 gena te LINE 1 ponavljajućih sljedova tijekom fetalnog razvoja sjemenika u čovjeka i u štakora
Title (english)Methylation of RB1, H19 genes and LINE 1 repetitive sequence during fetal development of testis in man and in rat
AuthorMarta Himelreich Perić
MentorAna Katušić Bojanac (mentor)
Committee memberDavor Ježek (predsjednik povjerenstva)
Committee memberFloriana Jakuš (član povjerenstva)
Committee memberMarko Hohšteter (član povjerenstva)
GranterUniversity of Zagreb
School of Medicine
Zagreb
Defense date and country2022-10-06, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Medical Biochemistry
Universal decimal classification
(UDC)		616 - Pathology. Clinical medicine
Abstract
Neki od uzroka muške neplodnost mogu imati ishodište u epigenetičkim poremećajima tijekom prenatalnog života. Cilj disertacije bio je istražiti DNA metilaciju LINE-1 transpozonskih ponavljajućih sljedova i diferencijalno metilirane regije (DMR) utisnutog gena H19 u tkivu fetalnog sjemenika čovjeka i štakora te RB1 tumorsupresorskog gena u čovjeka usporedno sa staničnom proliferacijom i izražajem tumor supresora RB1 te njegovih fosforiliranih oblika. DNA metilacija u fetalnom štakorskom sjemeniku značajno raste za LINE-1 od 16.5 do 21.5 dpc, a za H19 do 17.5 dpc. Analiza ljudskih uzoraka pokazuje visoku razinu metilacije LINE-1 tijekom trudnoće te značajno sniženje u pubertetu, a za H19 rast do kraja trudnoće, dok je RB1 tijekom trudnoće hipometiliran (ispod 5%). Izražaj biljega proliferacije Ki-67 u štakorskom sjemeniku značajno se smanjuje od 16.5 do 19.5 dpc kao i izražaj fosforiliranih RB1 proteina u odnosu na ukupan broj stanica i promjer kanalića, a zatim se povisuje (19.5 - 20.5 dpc). U ljudskim sjemenicima izražaj Ki-67 i fosforiliranih oblika RB1 u odnosu na ukupan broj stanica i promjer kanalića pada od prvog prema drugom tromjesječju, a od drugog prema trećem raste ukupni RB1 i dio fosforiliranih formi. Rezultati ovog rada značajni su kao baza za daljnje istraživanje uzroka neplodnosti ili tumora sjemenika koji mogu biti uzrokovani promjenom metilacije gena koji djeluju na stabilnost genoma, genomsko utiskivanje i regulaciju staničnog ciklusa.
Abstract (english)
Some of the causes of male infertility may have their origin in epigenetic disorders during prenatal life. The aim of the study was to investigate DNA methylation of LINE-1 transposon repetitive sequences and the imprinted differentially methylated region (DMR) of H19 gene in human and rat fetal testis and the RB1 tumor supressor gene in humans in parallel with the expression of RB1 protein and its phosphorylated forms. DNA methylation in the fetal rat testis increases significantly for LINE-1 from 16.5 to 21.5 dpc, and for H19 to 17.5 dpc. Analysis of human samples showed a high level of LINE-1 methylation during pregnancy with a significant decrease in puberty, and for H19 an increase until the end of pregnancy, while RB1 was hypomethylated during pregnancy (below 5%). The expression of Ki-67 proliferation marker in the rat testis is significantly reduced from 16.5 to 19.5 dpc as well as the expression of phosphorylated RB1 proteins from 16.5 and 19.5 relative to total cell number and tubular diameter, and is increased from 19.5 to 20.5. In human testes, the expression of Ki-67 and phosphorylated RB1 in relation to the total number of cells and the diameter of the tubules decreases from the first to the second trimester, and from the second to the third the total RB1 and a part of the phosphorylated forms increase. The results of this work are important as a basis for further research into the causes of infertility or testicular tumors that may be caused by altered methylation of genes that affect genome stability, genomic imprinting, and cell cycle regulation.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:105:820020
ProjectNumber: KK.01.1.1.01.0008
Title: Reproduktivna i regenerativna medicina - istraživanje novih platformi i potencijala
Leader: Ana Katušić Bojanac
Jurisdiction: eu
Funder: MZO
Study programmeTitle: Biomedicine and Health Sciences
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
Type of resourceText
Extent181 str.
File originBorn digital
Access conditionsOpen access
Embargo expiration date: 2024-10-06
Terms of useLicence In copyright icon
Created on2022-11-29 12:14:03