Dynamic epigenetic modifications during human fetal germ cell development

Germ cells are responsible for transferring genetic information from parents to offspring, highlighting the significance of normal germ cell development. Epigenetic modifications, which modify gene expression without changing the underlying DNA sequence, can affect the fate of germ cells. Abnormal epigenetic reprogramming will facilitate abnormal germ cell development; therefore, understanding of epigenetic reprogramming mechanisms can contribute to the discovery of medical interventions for reproductive disease. DNA methylation and histone modification are two main components of epigenetic modifications. Both of them play important roles in mammalian germ cells development. In human germ cells, very few observations about these epigenetic modifications have been reported. Therefore, this report aims to form the major epigenetic reprogramming study conducted in human fetal germ cells, establishing an accurate timeline of events pertaining to this process in human fetal germ cells. Specifically, this research is divided into understanding (1) the process of histone modifications in human fetal germ cells; (2) the reprogramming of DNA methylation and its related modifiers in human germ cell development; (3) the impact of chemical DNA demethylation in the expression of germ cell-specific genes and the meiotic genes in human in vitro and ex vivo. Studies in human fetal gonads indicated that histone modifications changed dynamically during human fetal germ cell development. Experiments addressing DNA methylation reprogramming in human fetal germ cells collectively reveal a trend towards DNA demethylation and reductions in 5-methylcytosine (5mC), in the instance of both fetal ovarian and testicular germ cells alike. Furthermore, 5mC was re-detected in human fetal testicular germ cells at fetal stage, but in human fetal ovarian germ cells after birth. The studies in human germ cells here demonstrated that the existence of 5mC and 5-hydroxymethylcytosine (5hmC) were synchronous rather than alternate. Determination of the levels of TET (ten-eleven translocation) proteins (TET 1, 2 and 3) reveal higher levels during the 1st trimester, with subsequent reductions in levels with gestations. Additional findings, from the studies in a human testicular germ cell tumor cell line, TCam-2 cells, and human fetal gonads, showed that treatments with DNA demethylating agents are linked to the activation and increase of post-migratory germ cell-specific genes along with meiotic genes in human. To conclude, the results from this study demonstrate that epigenetic changes, such as histone modification and DNA methylation, are dynamic in human germ cells, the precise nature of which necessitates further research.

Grantor dc:publisher

The University of Edinburgh

Year dc:date.issued

2017

Author dc:creator

• Zhou, Jieqian

Advisors dc:contributor.advisor

• Anderson, Richard
• De Sousa, Paul

• histone modifications
• DNA methylation
• human germ cell development

Language dc:language.iso

en

Handle dc:identifier.uri

http://hdl.handle.net/1842/23606

OAI identifier oai:identifier

oai:era.ed.ac.uk:1842/23606