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Roles of Milk Exosomes and Their MicroRNA Cargos in Perinatal Health in Mice
Cells utilize exosomes to transfer regulatory cargos from donor cells to recipient cells. A well-known cargo of exosomes are microRNAs which have a critical role in the posttranscriptional gene regulation in recipient cells. Until recently scientists believed that only endogenous microRNAs regulate genes in an organism. Our laboratory demonstrated that mammals absorb exosomes and their microRNAs from milk. Conducting a feeding study using a diet depleted of exosomes and RNAs, we provided evidence suggesting that dietary exosomes and microRNAs affect gene expression and metabolism, and depletion elicits distinct phenotypes in mice. However, availability and role of milk exosomes and microRNAs in embryo and newborns during gestation and lactation time remain elusive. The first chapter of this dissertation is addressing the role of milk exosomes and their miRNAs cargos in embryo development. Our findings suggest that dietary exosomes and microRNAs accumulate in embryos and placenta. Maternal consumption of an exosome and microRNA-depleted diet caused a decrease in litter size and postnatal survival compared to controls fed an exosome and microRNA sufficient diet, caused by a reduced expression of extracellular matrix components. The second chapter expands upon the role of maternal exosomes and microRNAs on postnatal growth of the newborns and their gut functions. This study was conducted by generating transgenic mice eliciting impaired exosome or microRNA biogenesis pathways. The results reveal the nutritional value of maternal exosomes and microRNAs during lactation for optimal growth of nursing pups and regulation of gut barrier and absorption. The third chapter of this dissertation represent a previous, unfinished project in our laboratory. The project does not relate to exosomes, but explored the role of HLCS in embryonic development. HLCS catalyzes the covalent attachment of the vitamin biotin to carboxylases and chromatin proteins. We developed an HLCS conditional knock out mice and demonstrated that knockout is embryonic lethal. This knock out mice shows potential as worthwhile model for future studies regarding the role of HLCS related pathways and biotin depletion in embryo development.
Nutrition|Molecular biology|Developmental biology
Sadri, Mahrou, "Roles of Milk Exosomes and Their MicroRNA Cargos in Perinatal Health in Mice" (2020). ETD collection for University of Nebraska - Lincoln. AAI28092092.