Importance of micro RNAs in developmental biology with respect to gametes and embryos

ABSTRACT

Background: Advances in the analyses of human and other higher eukaryotic genomes have disclosed a large fraction of the genetic material (ca 98%) which does not code for proteins. Major portion of this non-coding genome is in fact transcribed into an enormous repertoire of functional RNA molecules (ncRNAs) rather than encoding any proteins. Broadly ncRNAs fall into three size classes namely, ~20 nucleotides for the large family of microRNAs, to 25-200 nucleotides for other different families of small RNAs and finally to over thousands of nucleotides for macro ncRNAs involved in eukaryotic gene regulation. Among the ncRNAs that have been revolutionized our understanding of eukaryotic gene expression, microRNAs (miRNAs) have recently been emphasized extensively with enormous potential for playing their pivotal roles in diseases, fertility and development. The miRNAs are estimated to comprise 1­5% of animal genes or a given genome could encode nearly thousands of miRNAs. Moreover, a typical miRNA regulates hundreds of target genes and altogether they could target a large proportion of genes up to 30% of the genome. Review It was reviewed the involvement of miRNAs for reproductive biology in mammals known so far. Several studies expanding from identification and expression profiling to functional involvement of miRNAs in the ovary have been carried out in different animal species. Several studies highlighted the expression and regulation of some individual miRNAs in different ovarian cells especially in oocyte and granulosa cells. Furthermore the impact of miRNAs for embryonic development was considered. The well-orchestrated expression of genes that are derived from the maternal and/or embryonic genome is required for the onset and maintenance of distinct morphological changes during the embryonic development. Optimum regulation of genes or critical gene regulatory event in favor of early embryonic development have been shown directly (individual miRNAs study) or indirectly (disrupting miRNAs biogenesis) under the control of miRNAs. Finally, miRNA effects on DNA methylation pattern are reported by the review. Reversible DNA methylation and histone modifications are known to have profound effects on controlling gene expression. Correct DNA methylation patterns are paramount for the generation of functional gametes with pluripotency states, embryo development, placental function and the maintenance of genome architecture and expression in somatic cells. Aberrancies in both the epigenetic and in the miRNA regulation of genes have been documented to be important in diseases and early development. Interestingly, it has been evident that there is an effect of miRNAs on epigenetic machinery. On the other hand miRNA expression also found to be controlled by epigenetic mechanisms. Conclusion: Significant advancements have been made in recent years on understanding the involvement of miRNA's in ovarian function, gene regulation well as early embryonic development. Since this area of research is rapidly moving forward it is expected that a lot of information regarding miRNA-mediated posttranscriptional gene regulation and their epigenetic regulation in ruminant reproduction biology will be known within the next several years. Studies to identify the specific miRNAs, their target genes and post transcriptional regulatory network will further shed light on the importance of specific miRNA both for the development and function of reproductive tissues as well as disease condition. Once relevant miRNAs and functional targets are identified, possible clinical use for these molecules will represent the next front line and may lead to novel strategies for better enhancing or manipulating reproductive efficiency.