| dc.description.abstract | Fetal Alcohol Spectrum Disorder (FASD) is the most prevalent, yet completely preventable birth defect. Over the last half century, we have seen many milestones in fetal alcohol research, from the 1981 US Surgeon General warning to limit alcohol during pregnancy, to the 2005 US Surgeon General warning to avoid alcohol altogether, during pregnancy. Although major advancements, these health messages only provide a partial picture by focusing solely on maternal alcohol consumption. This research questions the maternal centric focus and sheds light on the implications of paternal alcohol use. By building upon recent research linking paternal alcohol consumption to fetal growth defects, this research brings the urgent message of the dangers of paternal alcohol exposure closer to clinical practice.
Using a clinically relevant mouse model, we first investigated the effects of maternal genetics on paternal alcohol exposure. We found that maternal factors have the capacity to modulate the fetal and placental changes induced by paternal alcohol consumption. Next, we tested the capacity of different doses of paternal alcohol to exert effects on fetal development. Interestingly, we found a biphasic dose response, with lower doses resulting in placental and fetal overgrowth and higher doses leading to fetal and placental growth deficiency. Equipped with the knowledge of a maternal-paternal crosstalk and a clinically relevant paternal alcohol dose that resulted in FASD-like growth restriction, we next implemented a multi-factorial model to evaluate the effects of maternal, paternal, and dual parental alcohol exposures on craniofacial development. The most severe form of FASD, Fetal Alcohol Syndrome, results in distinct craniofacial phenotypes and through this groundbreaking research we found that maternal, paternal, and dual parental alcohol exposure resulted in distinct craniofacial growth deficiencies. Finally, as neurological development is closely associated with craniofacial development, we investigated the lasting impact of maternal, paternal, and dual parental alcohol exposure on offspring behavior during adolescence and adulthood. Importantly, we found that these early life exposures led to long lasting impacts on health and behavior, providing support for the Developmental Origins of Health and Disease hypothesis. Collectively, these studies identify the father as a significant inducer and contributor to FASD. | |
