The dynamics of microRNA transcriptome in the bovine corpus luteum during its formation, function and regression. microRNA dynamics in the bovine corpus luteum

In dynamically developing tissues such as the Corpus Luteum is, microRNAs (miRNAs) are accepted as important modulators of post-transcriptional gene expression regulation. Using small RNA next-generation sequencing we profiled the expression of miRNAs in bovine CL at early CL (eCL, C1: d 1-2, C3: d 3-4, C5: d 5-7), mid CL (mCL, C8: d 8-12), late CL (lCL, C13: d 13-16) and regressed CL (rCL, C18: d 18+).The most abundantly expressed miRNAs irrespective of the cycle stage were annotated to bta-miR-21-5p and bta-miR-143, which accounts for more than 40% of the total reads. Further, 42 miRNAs were found to be differentially expressed (DE) in the CL at each stage (mid-, late- and regressed CL) relative to their expression in the early CL. Another 24, 11 and 21 miRNAs were unique to and only DE in the early versus the mid, late and regressed CL, respectively. DE luteal miRNAs (167 out of 793 annotated miRNAs) were further grouped into eight distinct clusters by the self-organizing tree algorithm (SOTA). Half of the clusters contain miRNAs with low-expression, whilst the other half contains miRNA with high-expression levels during early luteal phase. Prediction analysis for DE miRNAs common to early CL and the other three cycle stages resulted in genes involved in CL formation, functionalization and CL regression. Prominent target genes of the DE miRNAs include: VEGFA, HIF1A, FGF2, MMPs, THBS1, TIMP-1, TGFb1 and STAT3. Functional annotation of miRNAs unique to and only DE in eCL vs. mCL, eCL vs. lCL and eCL vs. rCL resulted in pathways involved with fatty acid synthesis, TGFb- signaling; axon guidance, oxytocin and prolactin signaling, and ECM-receptor interaction, respectively.