| dc.description.abstract | This dissertation utilizes a mouse model to investigate how paternal alcohol consumption affects in vitro fertilization (IVF) success, assisted reproductive technology (ART) fetoplacental development, the transcriptional profiles of sperm and epididymis, the male microbiome-metabolome, and the female response to seminal fluid. Previous alcohol research concentrates on the maternal influence during gestation. Males provide half of the genetic material and should be considered for their contributions to pregnancy and offspring development. Our earlier studies revealed that preconception paternal alcohol alters fetoplacental growth and F1 offspring metabolism. These experiments support our hypothesis that the epigenetic memory of alcohol is retained by sperm and is inherited by offspring via biological mechanisms, such as RNA and histones.
Expanding on this, we employed a clinically relevant mouse model of voluntary paternal alcohol consumption. We observe preconception paternal alcohol exposure decreases IVF embryo survival and pregnancy success rates in a dose-dependent manner. By analyzing embryonic RNA profiles, we find that preconception paternal alcohol exposure disrupts placental gene expression and modifies mitochondrial function and oxidative phosphorylation. Histologically, we identify lasting impacts on late-term placental organization. Using RNA analyses and mitochondrial DNA counts, we establish paternal cessation of ethanol exposure for one month provides limited epigenetic recovery. We then focus on bioinformatic analyses of alcohol, with or without saccharin, exposed male gastrointestinal microbiomes and blood metabolite concentrations where we show altered microbial populations and increased acetic acid levels in EtOH combined with saccharin. Lastly, using RNA sequencing, we characterize changes in gene expression of the female tract after alcohol-exposed seminal plasma insemination. These studies highlight the necessity to change reproductive health messaging for family planning and stress the hazards of parental alcohol use.
Discoveries from our lab elucidate combined extrinsic factors that are inherited by offspring. These studies contribute to the developmental toxicology field by examining the influence of paternal alcohol consumption on multiple facets of reproduction. Future explorations concentrating on alcohol-exposed sperm mitochondrial function can use similar methods to assess contributions to the sperm epigenome. This effort will assist in discerning the mechanism(s) by which alcohol modifies spermatozoa and transmits adverse health conditions intergenerationally and, possibly, transgenerationally. | |
