Maternal RNAs are synthesized by the oocyte during its growth, some of them are utilized for oocyte-specific processes and metabolism, others are stored and used during early development before embryonic genome activation. The appropriate expression of complex sets of genes is needed for oocyte maturation and early embryo development. In spite of the basic role of non-coding RNAs in the regulation of gene expression, few studies have analyzed their role in human oocytes. In this study, we identified the microRNAs expressed in human MII oocytes and found that some of them are able to control pluripotency, chromatin remodeling and early embryo development. We demonstrated that 12 microRNAs are differentially expressed in women of advanced reproductive age and by bioinformatics analysis we identified their mRNA targets, expressed in human oocytes and involved in the regulation of pathways altered in reproductive aging. Finally, we found the upregulation of miR-29a-3p, miR-203a-3p and miR-494-3p, evolutionary conserved microRNAs, also in aged mouse oocytes and demonstrated that their overexpression is antithetically correlated with the downregulation of Dnmt3a, Dnmt3b, Pten and Tfam. We propose that oocyte microRNAs perform an important regulatory function in human female germ cells and their altered regulation could explain the changes occurring in oocyte aging.

MicroRNAs Are Stored in Human MII Oocyte and Their Expression Profile Changes in Reproductive Aging

Battaglia R;RAGUSA, MARCO;BARBAGALLO, DAVIDE;La Ferlita A;Scollo P;PURRELLO, Michele;DI PIETRO, Cinzia Santa
2016

Abstract

Maternal RNAs are synthesized by the oocyte during its growth, some of them are utilized for oocyte-specific processes and metabolism, others are stored and used during early development before embryonic genome activation. The appropriate expression of complex sets of genes is needed for oocyte maturation and early embryo development. In spite of the basic role of non-coding RNAs in the regulation of gene expression, few studies have analyzed their role in human oocytes. In this study, we identified the microRNAs expressed in human MII oocytes and found that some of them are able to control pluripotency, chromatin remodeling and early embryo development. We demonstrated that 12 microRNAs are differentially expressed in women of advanced reproductive age and by bioinformatics analysis we identified their mRNA targets, expressed in human oocytes and involved in the regulation of pathways altered in reproductive aging. Finally, we found the upregulation of miR-29a-3p, miR-203a-3p and miR-494-3p, evolutionary conserved microRNAs, also in aged mouse oocytes and demonstrated that their overexpression is antithetically correlated with the downregulation of Dnmt3a, Dnmt3b, Pten and Tfam. We propose that oocyte microRNAs perform an important regulatory function in human female germ cells and their altered regulation could explain the changes occurring in oocyte aging.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11769/20271
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