213 Comparative single-cell transcriptomics uncovers key regulatory mechanisms in bovine placental development.

Abstract Pregnancy loss in cattle imposes a significant financial burden on producers. Successful pregnancy relies on a complex interplay of biological processes, including the development and maintenance of the placenta. The placenta facilitates nutrient transport, gas exchange, and waste removal as the primary interface between the mother and fetus. Disruptions in placental development can lead to pregnancy failure, clearly highlighting the need to identify essential mechanisms that support pregnancy. Understanding these processes, both those unique to cattle and those shared across species, may reveal key genes and genomic regions for improved genetic selection and novel strategies to reduce pregnancy loss. This study aimed to integrate single-cell transcriptomic data from cattle with data from other mammalian species across developmental stages. Comparative analysis of early post-implantation single-cell RNA sequencing (scRNA-seq) data from bovine (n=3) and ovine (n=3) placenta identified distinct gene expression patterns, including SNAI1, SNAI2, VIM, CDH1, ZEB1, and CLDN4. These genes are involved in epithelial to mesenchymal transition (EMT), a well-characterized and conserved process in placental development among species with invasive placentation such as humans and rodents. This suggests conservation of EMT during early bovine and ovine pregnancy. Conversely, integration of scRNA-seq data from bovine (n=4) and human (n=4) placenta during the second trimester revealed conservation of immune cell populations, including natural killer (NK) cells, but marked differences in trophoblast cell types and gene expression profiles. These findings underscore the unique molecular characteristics of the bovine placenta during pregnancy maintenance. In summary, cross-species integration of scRNA-seq data provided insights into both conserved and species-specific cell types and mechanisms governing bovine pregnancy establishment and maintenance. This work provides valuable insights into pathways critical for pregnancy establishment and, when disrupted, potential causes of pregnancy loss. Ultimately, this work aims to support both beef and dairy operations by identifying novel ways to reduce pregnancy loss.