Epigenome, consisting of epigenetic marks such as DNA methylation and histone modifications, is essential for the normal development of a multicellular organism. Cell-type-specific epigenetic profiles for appropriate gene function will be formed and inherited by the daughter cells. Changes in the epigenome are essential for normal development, but are also induced by environmental exposures, diseases and stochastic events.
Unraveling the molecular mechanisms of environmental effects on embryonic development will clarify the fundamental phenomena, the roles of nature and nurture in our phenotypes. In addition to the etiology of complex phenotypes, we will reveal biomarkers, which will advance personalized medicine and enable retailed treatments and support for affected individuals.
Prenatal alcohol exposure is one of the most harmful environmental factors, affecting permanently 3-5 % of individuals in the Western world. Its consequence fetal alcohol spectrum disorders (FASD) is an umbrella term for all alcohol-induced developmental disorders including a broad spectrum of permanent structural, physiological, neurocognitive and behavioural disorders as well as restricted growth. Owing to the complex, highly variable phenotype and lack of proper diagnostic tools, FASD is severely underdiagnosed.
The purpose of the project is to clarify the etiology of FASD and to discover molecular biomarkers for diagnostics of alcohol-induced developmental disorders. Our unique epiFASD cohort consists of biological samples and developmental information of prenatally alcohol exposed newborns. The research is conducted in cooperation with the HAL outpatient clinic of the Helsinki University Central Hospital.
Assisted reproductive treatments have resulted in more than seven million children since 1978. According to Finnish institute of health and welfare, 5.4 % of the children born in Finland in 2016 were derived from IVF treatments. Although the results are impressive and the children are generally healthy, they have been associated with an increased risk of low birth weight and preterm birth. Low birth weight, in turn, has been linked to an increased risk for heart and vascular diseases. Altered levels of DNA methylation, one of the most studied epigenetic mark, have been observed in different human as well as mouse tissues derived from IVF pregnancies. This suggests that ART protocol - even without infertility as a confounding factor - can affect the epigenome.
In addition to the factors behind infertility, our aim is to determine the effects of ART methods on the epigenome and on the life-long health of IVF derived individuals. We also explore differences between various fertility treatment methods and how these methods could be developed further in the future. For this purpose, we are collecting an exceptional epiART cohort of IVF derived newborns, both biological samples and follow-up information. The epiART research is conducted in cooperation with the Reproductive Medicine Unit of the Helsinki University Central Hospital.
By using modern methods and model organisms such as embryonic stem cells and mouse models we are able to focus on the effects of environment on the first cells in an embryo. Especially we are interested in the period of epigenetic reprogramming in the beginning of the pregnancy. This period is fundamental for normal development: it returns totipotency for the first cells of a new individual and cell type-specific epigenetic profiles for adequate gene function will be formed again. This period appears to be particularly sensitive to environmental influences.
We have shown for the first time that alcohol can affect adult phenotype by altering the epigenotype of early mouse embryo. The offspring phenotype was reminiscent of human FASD with craniofacial dysmorphology, postnatal growth restriction and structural changes in central nervous system.