Effects of prenatal alcohol exposure on the epigenome, gene expression and development

Heidi Marjonen

Research output: ThesisDoctoral ThesisCollection of Articles

Abstract

Prenatal alcohol exposure affects the developing fetus and causes a wide range of physical and neurological abnormalities. The phenotype is generally described as fetal alcohol spectrum disorders (FASD) which is used as an umbrella term for all disorders caused by prenatal alcohol exposure. To date, the prevalence of FASD ranges from 1-5% in Finland. Even though, a wide range of the phenotypic characteristics have been identified, the underlying molecular mechanisms of FASD have remained unclear. Previous studies have suggested that epigenetic mechanisms represent a link between adverse early-life conditions and health consequences. Since the epigenome has a critical role during embryonic development by mediating the gene-environment interactions, this has raised interest in exploring the epigenetic changes behind FASD. The aim of this thesis was to approach the subject of prenatal alcohol exposure from the epigenetic point of view by exploring the associations between the molecular changes and the phenotypic characteristics. In our investigations of prenatal alcohol exposure, we exploited both a mouse model and human samples. The results obtained with the mouse model underline the vulnerability of the early embryo to alcohol-induced effects. Genome-wide gene expression analysis of adolescent male hippocampi revealed altered expression of several genes. Moreover, an MRI study of adult male brains in mice revealed asymmetry in the volume of the hippocampi: the left hippocampus was significantly larger than the right in alcohol-exposed offspring. Furthermore, we observed expression changes in growth-related imprinted genes in mouse embryos and placentas. Our human results highlight the importance of taking into account individual’s genetic characteristics when examining the background behind the alcohol disorder phenotype. We detected a single nucleotide polymorphism rs10732516G/A within the imprinting control region of the Insulin-like growth factor 2 (IGF2)/H19 imprinted locus and investigated the locus in a new way. As a result, we detected genotype-specific DNA methylation changes in the imprinting control region in alcohol-exposed placentas. Furthermore, the most significant finding was genotype-specific changes in the head circumference of the alcohol-exposed newborns.
Original languageEnglish
Supervisors/Advisors
  • Kaminen-Ahola, Nina , Supervisor
Place of PublicationHelsinki
Publisher
Print ISBNs978-951-51-4574-1
Electronic ISBNs978-951-51-4575-8
Publication statusPublished - 2018
MoE publication typeG5 Doctoral dissertation (article)

Bibliographical note

M1 - 123 s. + liitteet

Fields of Science

  • Prenatal Exposure Delayed Effects
  • Ethanol
  • Alcohol-Related Disorders
  • Epigenesis, Genetic
  • DNA Methylation
  • Genomic Imprinting
  • Embryonic Development
  • Fetus
  • +drug effects
  • Fetal Growth Retardation
  • +genetics
  • Infant, Newborn
  • Brain
  • Hippocampus
  • Placenta
  • Pregnancy
  • Insulin-Like Growth Factor II
  • snRNP Core Proteins
  • RNA, Long Noncoding
  • Mice
  • Gene Expression Profiling
  • Pregnant Women
  • 3111 Biomedicine

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