Transcriptomic analysis of primate placentas and novel rhesus trophoblast cell lines informs investigations of human placentation

Background: Proper placentation, including trophoblast differentiation and function, is essential for the health and well-being of both the mother and baby throughout pregnancy. Placental abnormalities that occur during the early stages of development are thought to contribute to preeclampsia and other placenta-related pregnancy complications. However, relatively little is known about these stages in humans due to obvious ethical and technical limitations. Rhesus macaques are considered an ideal surrogate for studying human placentation, but the unclear translatability of known human placental markers and lack of accessible rhesus trophoblast cell lines can impede the use of this animal model. Results: Here, we performed a cross-species transcriptomic comparison of human and rhesus placenta and determined that while the majority of human placental marker genes (HPGs) were similarly expressed, 952 differentially expressed genes (DEGs) were identified between the two species. Functional enrichment analysis of the 447 human-upregulated DEGs, including ADAM12, ERVW-1, KISS1, LGALS13, PAPPA2, PGF, and SIGLEC6, revealed over-representation of genes implicated in preeclampsia and other pregnancy disorders. Additionally, to enable in vitro functional studies of early placentation, we generated and thoroughly characterized two highly pure first trimester telomerase (TERT) immortalized rhesus trophoblast cell lines (iRP-D26 and iRP-D28A) that retained crucial features of isolated primary trophoblasts. Conclusions: Overall, our findings help elucidate the molecular translatability between human and rhesus placenta and reveal notable expression differences in several HPGs and genes implicated in pregnancy complications that should be considered when using the rhesus animal model to study normal and pathological human placentation.