GENE REGULATION AND EPIGENETIC LANDSCAPES OF THE MATERNAL-FETAL INTERFACE DURING EARLY GESTATION IN CATTLE

Ashley Destin

Successful gestation is pivotal to maintaining the cattle herds that are the backbone of the cattle industry in the United States. Pregnancy loss represents a two-factor economic loss: direct losses related to labor and management, and indirect losses due to a reduction in reproductive efficiency. Research has demonstrated that failures of the placenta contribute to pregnancy losses, as successful gestation relies on the development and complex regulation of proper placental development. While advances in sequencing technologies and genomic analysis have greatly improved the overall understanding of placental biology, the complexity of gene regulatory networks and epigenetic mechanisms, including DNA methylation, means that many aspects of placental development remain poorly understood.To investigate epigenetic regulatory mechanisms contributing to placenta and placentome development, placentome samples were collected from Holstein cows at gestational day 52 for whole-genome DNA methylation analysis. Placentomes were manually dissected into the maternal (caruncle) and fetal (cotyledon) components for high-molecular weight DNA isolation and sequencing using a PacBio Revio instrument. These sequences were then aligned and annotated to the bovine reference genome (ARS-UCD2.0) to identify differentially methylated regions (DMRs). Overall, 2,186 DMRs were identified in the cotyledon compared with the caruncle, highlighting dynamic differences in gene regulation between maternal and fetal tissues. Almost 76% of hypomethylated DMRs were located within introns and intergenic regions, indicating possible roles in regulation of alternative splicing, enhancer activity, and cellular differentiation. Biological process enrichment of differentially methylated genes revealed distinct pathways potentially regulated by DNA methylation in both tissues. Hypermethylated genes in the cotyledon were significantly enriched in pathways related to immunomodulation, emphasizing the importance of immune function at the maternal-fetal interface. Hypomethylated genes exhibited greater enrichment of the nervous system development pathway, supporting the significance of the brain-placenta axis in cattle. The results from this study provide greater insight into the role of DNA methylation in regulation of placental development, fetal growth, and pregnancy maintenance, and lay the groundwork for additional research into the specific regulatory functions of DNA methylation. A more comprehensive understanding of the regulatory mechanisms involved in placental development may ultimately contribute to greater reproductive efficiency in cattle.

GENE REGULATION AND EPIGENETIC LANDSCAPES OF THE MATERNAL-FETAL INTERFACE DURING EARLY GESTATION IN CATTLE

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