Abstract
The recent discovery of microRNAs (miRNAs) in human reproductive tissues and cells indicates a possible functional role in reproductive function. However, the studies published to date in female reproductive tissues/cells and embryos are inconclusive and sometimes controversial. In order to update the knowledge of this field, the present study aimed to discuss, through a systematic review, the role of miRNAs in female human reproduction and early embryogenesis. We conducted a systematic review of the published literature in MEDLINE and EMBASE databases through June 2018 (plus a complementary search until July 2019), in accordance with the PRISMA guidelines. We have included descriptive and observational studies, in which fertile/infertile women were well-defined. The primary outcome was the miRNA expression in ovaries, oocytes, extracellular vesicles, and embryos. We identified 25,204 articles, of which 28 were selected for qualitative analysis: 18 in ovaries and extracellular vesicles, three in oocytes, and seven in embryos. The present systematic review of descriptive and observational studies demonstrates that aberrant miRNA expression in female reproductive tissues/cells and embryos is related with infertility and embryogenesis errors. The expression of specific miRNAs, particularly in extracellular vesicles, may be used in the future as biomarkers of infertility and prognostic tools of embryo development.
Highlights
MicroRNAs are single-stranded RNA molecules from 16–28 nucleotides in length that function to regulate gene expression by means of the formation of semi-complementary structures between mRNA and miRNAs in 30 untranslated regions (30 UTR)(in plants the mRNA-miRNA interaction is near perfect, whereas in animals, miRNAs bind in semi-complementarity with mRNA encoding regions) [1,2]
One hundred and seventy-six of these 324 articles were excluded because they did not meet the inclusion/exclusion criteria, while 70 articles were excluded because they were review articles, two articles were excluded because their full-text was not available, 41 articles were excluded because they were studies in male reproductive tissues/cells, and seven articles were excluded because they did not reach the quality assessment threshold
On the basis of the results of the present analysis, these data strongly suggest that the presence and expression levels of miRNAs in the aforementioned cells/tissues are related with female fertility and embryo development
Summary
MicroRNAs (miRNAs) are single-stranded RNA molecules from 16–28 nucleotides in length (www.mirbase.org) that function to regulate gene expression by means of the formation of semi-complementary structures between mRNA and miRNAs in 30 untranslated regions (30 UTR)(in plants the mRNA-miRNA interaction is near perfect, whereas in animals, miRNAs bind in semi-complementarity with mRNA encoding regions) [1,2]. MicroRNAs (miRNAs) are single-stranded RNA molecules from 16–28 nucleotides in length (www.mirbase.org) that function to regulate gene expression by means of the formation of semi-complementary structures between mRNA and miRNAs in 30 untranslated regions (30 UTR). A very recent in silico high-throughput experimental strategy estimated that about 2,300 mature miRNAs exist in humans, 1,982 of which are currently annotated in miRBase v.22.1 (www.mirbase.org). In 2002, a landmark article reported the presence of small RNAs in sperm cells [7]; later, the same authors described that they were probably miRNAs [8]. Other authors described the presence of miRNAs in all human reproductive tissues and cells [9,10], evidencing the role in male [11]
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