Defining the rhesus macaque placental miRNAome: Conservation of expression of placental miRNA clusters between the macaque and human

Objective: Expression of microRNAs (miRNAs) in the human placenta is dynamic across gestation, with expression of miRNAs belonging to the C14MC, C19MC and miR-371-3 clusters. Specifically, miRNAs within the C19MC cluster are exclusively expressed in primates with predominant expression in the placenta. Non-human primates can be utilized to study developmental processes of placentation in vivo that cannot be assessed in the human placenta, however, miRNA expression has not been defined in the macaque placenta. Our objective was to profile miRNAs in the macaque placenta, hypothesizing that expression is conserved between the macaque and human placenta.

Methods: Total RNA from first trimester and term macaque placentas (n = 4 per group) was analyzed through RNA-sequencing and validated by quantitative real-time PCR (qRT-PCR).

Results: A total of 607 pre-miRNAs previously annotated in the macaque reference database (miRBase21) were detected, and 166 miRNAs were differentially expressed between first trimester and term placentas. A total of 457 unannotated sequences were detected and deemed candidate novel miRNAs by miRDeep2 software. Differential expression was confirmed for six of nine miRNAs evaluated by qRT-PCR. Comparative analysis demonstrated expression of several miRNA orthologs of human pregnancy-associated miRNA clusters in the macaque placenta.

Conclusions: Profiling placental miRNAs of the macaque revealed conserved expression of a number of miRNAs within the C14MC, C19MC and miR-371-3 clusters between the human and macaque. These results establish non-human primates as a model for human placentation and miRNA biology, with the prediction of their functional significance in placental development and function.