The role of DNA methylation in human spermatogenesis

master's thesis

• Title (croatian): Uloga DNA metilacije u humanoj spermatogenezi
• Author: Inbar Shafran
• Mentor: Ana Katušić Bojanac (mentor)
• Committee member: Ana Katušić Bojanac (predsjednik povjerenstva)
• Committee member: Nino Sinčić (član povjerenstva)
• Committee member: Ljiljana Šerman (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2022-03-11, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Surgery

Abstract

What is the story behind the term “germ cell epigenetics”, what can we learn from the changes in methylation during gametogenesis, and how could it be put to good use? This thesis aims to explain how changes in the DNA methylation affects the development of primordial cells into mature sperm.
Methylation is the epigenetic process controlling what genes will be expressed and what genes will be silenced. Epigenetics can be viewed as the environmental inheritance we get from our ancestors. It reflects changes that occur due to normal aging (development) but also environmental influences. Alarmingly, our epigenome reflects not only our lifestyle choices but also the experiences of our parents and perhaps also grandparents.
Some methylation processes are inherited from the father and some from the mother, part of which reflects the imprinting process. Today, it is known that some genes in specific sites will be maternally imprinted and others paternally imprinted, making each parent contribute to various specific cells. This is all done by the process of methylation.
The development of the oocyte and sperm starts in the embryonic period and varies drastically. Male developing germ cells show changes in their methylation process already during the fetal period and continue during spermatogenesis. Sperm of infertile males have been shown to carry methylation defects and there is a danger of passing the methylation errors to the next generation. Thus, understanding the male germ cell methylome can help us understand its vulnerabilities, as well as identify factors that may influence its methylation.
I hope that by learning more about these processes, we will be able to understand ourselves better and create better diagnostic and treatment options for men with infertility problems, as well as help us create personalized preventive approaches for those problems.

Abstract (croatian)

Što stoji iza riječi “epigenetika spolnih stanica”, što možemo naučiti iz promjena u metilaciji tijekom gametogeneze i kako se to može dobro iskoristiti? Ovaj rad će objasniti razvoj primordijalnih stanica u zrele spermije u kontekstu promjena u procesu DNA metilacije.
Metilacija je epigenetski proces koji kontrolira koji će geni biti izraženi, a koji geni će biti utišani. Epigenetika se može promatrati kao ekološko naslijeđe koje dobivamo od naših predaka. Odražava također i promjene do kojih dolazi zbog normalnog starenja (razvoja), ali i utjecaja okoline. Zaprepaštujuće, naš epigenom odražava ne samo naš način života, već i iskustva naših roditelja, a možda i baka i djedova.
Neki procesi metilacije su naslijeđeni od oca, a neki od majke, od kojih dio odražava proces utiskivanja. Danas je poznato da će neki geni na određenim mjestima biti utisnuti s majčine, a drugi s očeve strane, čineći da svaki roditelj doprinosi različitosti specifičnih stanica sve se to postiže procesom metilacije.
Razvoj oocita i spermija počinje u embrionalnom razdoblju i drastično varira. Muške zametne stanice u razvoju pokazuju promjene metilacije već tijekom fetalnog razdoblja i kasnije u spermatogenezi. Pokazalo se da spermiji neplodnih muškaraca imaju defekte DNA metilacije. Međutim, postoji opasnost od prenošenja pogrešnih metilacijskih obrazaca na sljedeću generaciju. Dakle, razumijevanje metiloma muških zametnih stanica može nam pomoći razumjeti njihovu ranjivost kao i čimbenike koji na nju mogu utjecati.
Nadam se da ćemo, učeći više o tim procesima, moći bolje razumjeti sebe i stvoriti bolje dijagnostičke i terapijske mogućnosti, pomažući muškarcima s problemima neplodnosti kao i u razvoju personalizirane preventivne medicine.

• Keywords: DNA Methylation; Epigenome; Semen; Infertility; Male; Spermatozoa; Epigenesis; Genetic; Spermatogenesis; Gametogenesis; Oocytes
• Keywords (croatian): DNK metilacija; Epigenom; Sjeme; Neplodnost; muškarac; Spermatozoidi; Epigeneza; genetski; Spermatogeneza; Gametogeneza; Jajne stanice
• Language: english
• URN:NBN: urn:nbn:hr:105:186164
• Study programme: Title: Medicine (in English language); 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: 2022-12-22 10:34:29