journal article Open Access Jun 14, 2019

Cell-Free, Embryo-Specific sncRNA as a Molecular Biological Bridge between Patient Fertility and IVF Efficiency

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Abstract
Small noncoding RNAs (sncRNAs) are key regulators of the majority of human reproduction events. Understanding their function in the context of gametogenesis and embryogenesis will allow insight into the possible causes of in vitro fertilization (IVF) implantation failure. The aim of this study was to analyze the sncRNA expression profile of the spent culture media on day 4 after fertilization and to reveal a relationship with the morphofunctional characteristics of gametes and resultant embryos, in particular, with the embryo development and implantation potential. Thereto, cell-free, embryo-specific sncRNAs were identified by next generation sequencing (NGS) and quantified by reverse transcription coupled with polymerase chain reaction (RT-PCR) in real-time. Significant differences in the expression level of let-7b-5p, let-7i-5p, piR020401, piR16735, piR19675, piR20326, and piR17716 were revealed between embryo groups of various morphological gradings. Statistically significant correlations were found between the expression profiles of piR16735 and piR020401 with the oocyte-cumulus complex number, let-7b-5p and piR020401 with metaphase II oocyte and two pronuclei embryo numbers, let-7i-5p and piR20497 with the spermatozoid count per milliliter of ejaculate, piR19675 with the percentage of linearly motile spermatozoids, let-7b-5p with the embryo development grade, and let-7i-5p with embryo implantation. According to partial least squares discriminant analysis (PLS-DA), the expression levels of let-7i-5p (Variable Importance in Projection score (VIP) = 1.6262), piR020401 (VIP = 1.45281), and piR20497 (VIP = 1.42765) have the strongest influences on the implantation outcome.
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References
65
[1]
Gardner "Assessment of human embryo development using morphological criteria in an era of time-lapse, algorithms and ‘OMICS’: Is looking good still important?" Mol. Hum. Reprod. (2016) 10.1093/molehr/gaw057
[2]
Gardner, D.K., and Schoolcraft, W.B. (1999). In-vitro culture of human blastocysts. Towards Reproductive Certainty: Infertility and Genetics Beyond 1999: The Plenary Proceedings of the 11th World Congress on In Vitro Fertilization and Human Reproductive Genetics, Parthenon Press.
[3]
Gardner "Noninvasive assessment of human embryo nutrient consumption as a measure of developmental potential" Fertil. Steril. (2001) 10.1016/s0015-0282(01)02888-6
[4]
Linck "A proteomic analysis of mammalian preimplantation embryonic development" Reproduction (2005) 10.1530/rep.1.00854
[5]
Poli "Characterization and quantification of proteins secreted by single human embryos prior to implantation" EMBO Mol. Med. (2015) 10.15252/emmm.201505344
[6]
Hale "Small RNA regulation of reproductive function" Mol. Reprod. Dev. (2014) 10.1002/mrd.22272
[7]
Chua "MicroRNAs: Biogenesis, function and applications" Curr. Opin. Mol. Ther. (2009)
[8]
Houwing "A role for Piwi and piRNAs in germ cell maintenance and transposon silencing in Zebrafish" Cell (2007) 10.1016/j.cell.2007.03.026
[9]
Girard "A germline-specific class of small RNAs binds mammalian Piwi proteins" Nature (2006) 10.1038/nature04917
[10]
Hirakata "piRNA biogenesis in the germline: From transcription of piRNA genomic sources to piRNA maturation" Biochim. Biophys. Acta Gene Regul. Mech. (2016) 10.1016/j.bbagrm.2015.09.002
[11]
Poor ovarian response in women undergoing in vitro fertilization is associated with altered microRNA expression in cumulus cells

Cengiz Karakaya, Ozlem Guzeloglu-Kayisli, Asli Uyar et al.

Fertility and Sterility 2015 10.1016/j.fertnstert.2015.02.035
[12]
Machtinger "Extracellular microRNAs in follicular fluid and their potential association with oocyte fertilization and embryo quality: An exploratory study" J. Assist. Reprod. Genet. (2017) 10.1007/s10815-017-0876-8
[13]
Sang "Identification of MicroRNAs in Human Follicular Fluid: Characterization of MicroRNAs That Govern Steroidogenesis in Vitro and Are Associated With Polycystic Ovary Syndrome in Vivo" J. Clin. Endocrinol. Metab. (2013) 10.1210/jc.2013-1715
[14]
Battaglia "MicroRNAs Are Stored in Human MII Oocyte and Their Expression Profile Changes in Reproductive Aging" Biol. Reprod. (2016) 10.1095/biolreprod.116.142711
[15]
Hagos "Expression analysis of regulatory microRNAs in bovine cumulus oocyte complex and preimplantation embryos" Zygote (2013) 10.1017/s0967199411000566
[16]
Roovers "Piwi Proteins and piRNAs in Mammalian Oocytes and Early Embryos" Cell Rep. (2015) 10.1016/j.celrep.2015.02.062
[17]
Luo "Small non-coding RNAs and their associated proteins in spermatogenesis" Gene (2016) 10.1016/j.gene.2015.12.020
[18]
Yuan "Sperm-borne miRNAs and endo-siRNAs are important for fertilization and preimplantation embryonic development" Development (2016)
[19]
Svoboda "The role of miRNAs and endogenous siRNAs in maternal-to-zygotic reprogramming and the establishment of pluripotency" EMBO Rep. (2010) 10.1038/embor.2010.102
[20]
Giraldez "Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs" Science (2006) 10.1126/science.1122689
[21]
Siomi "PIWI-interacting small RNAs: The vanguard of genome defence" Nat. Rev. Mol. Cell Biol. (2011) 10.1038/nrm3089
[22]
Yang "Association of the peripheral blood levels of circulating microRNAs with both recurrent miscarriage and the outcomes of embryo transfer in an in vitro fertilization process" J. Transl. Med. (2018) 10.1186/s12967-018-1556-x
[23]
Capalbo "MicroRNAs in spent blastocyst culture medium are derived from trophectoderm cells and can be explored for human embryo reproductive competence assessment" Fertil. Steril. (2016) 10.1016/j.fertnstert.2015.09.014
[24]
Noli "Human Embryos Created by Embryo Splitting Secrete Significantly Lower Levels of miRNA-30c" Stem Cells Dev. (2016) 10.1089/scd.2016.0212
[25]
MicroRNA expression in the human blastocyst

Evan M. Rosenbluth, Dawne N. Shelton, Amy E.T. Sparks et al.

Fertility and Sterility 2013 10.1016/j.fertnstert.2012.11.001
[26]
No "Enhanced in vitro maturation of canine oocytes by oviduct epithelial cell co-culture" Theriogenology (2018) 10.1016/j.theriogenology.2017.09.002
[27]
Ji "The optimum number of oocytes in IVF treatment: An analysis of 2455 cycles in China" Hum. Reprod. (2013) 10.1093/humrep/det303
[28]
Chen "Optimum oocyte retrieved and transfer strategy in young women with normal ovarian reserve undergoing a long treatment protocol: A retrospective cohort study" J. Assist. Reprod. Genet. (2015) 10.1007/s10815-015-0571-6
[29]
La Ferlita, A., Battaglia, R., Andronico, F., Caruso, S., Cianci, A., Purrello, M., and Di Pietro, C. (2018). Non-Coding RNAs in Endometrial Physiopathology. Int. J. Mol. Sci., 19. 10.3390/ijms19072120
[30]
Platt "Mammalian transposable elements and their impacts on genome evolution" Chromosom. Res. (2018) 10.1007/s10577-017-9570-z
[31]
Russell "Bovine piRNA-like RNAs are associated with both transposable elements and mRNAs" Reproduction (2017) 10.1530/rep-16-0620
[32]
Sobala "Transfer RNA-derived fragments: Origins, processing, and functions" Wiley Interdiscip. Rev. RNA (2011) 10.1002/wrna.96
[33]
Spies "TRAMP-mediated RNA surveillance prevents spurious entry of RNAs into the Schizosaccharomyces pombe siRNA pathway" Nat. Struct. Mol. Biol. (2008) 10.1038/nsmb.1481
[34]
Saito "A regulatory circuit for piwi by the large Maf gene traffic jam in Drosophila" Nature (2009) 10.1038/nature08501
[35]
Robine "A Broadly Conserved Pathway Generates 3′UTR-Directed Primary piRNAs" Curr. Biol. (2009) 10.1016/j.cub.2009.11.064
[36]
Hirano "Small RNA profiling and characterization of piRNA clusters in the adult testes of the common marmoset, a model primate" RNA (2014) 10.1261/rna.045310.114
[37]
Zhang "MIWI and piRNA-mediated cleavage of messenger RNAs in mouse testes" Cell Res. (2015) 10.1038/cr.2015.4
[38]
Gou "Pachytene piRNAs instruct massive mRNA elimination during late spermiogenesis" Cell Res. (2014) 10.1038/cr.2014.41
[39]
Rouget "Maternal mRNA deadenylation and decay by the piRNA pathway in the early Drosophila embryo" Nature (2010) 10.1038/nature09465
[40]
Roth "Protein expression of the transcription factors DMRT1, TCLF5, and OCT4 in selected germ cell neoplasms of the testis" Hum. Pathol. (2018) 10.1016/j.humpath.2018.07.019
[41]
Duquette "Rho GTPases in embryonic development" Small GTPases (2014) 10.4161/sgtp.29716
[42]
Ringrose "Epigenetic Regulation of Cellular Memory by the Polycomb and Trithorax Group Proteins" Annu. Rev. Genet. (2004) 10.1146/annurev.genet.38.072902.091907
[43]
Lund "Polycomb complexes and silencing mechanisms" Curr. Opin. Cell Biol. (2004) 10.1016/j.ceb.2004.03.010
[44]
Otte "Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation" Nat. Genet. (1999) 10.1038/70602
[45]
Shao "Stabilization of Chromatin Structure by PRC1, a Polycomb Complex" Cell (1999) 10.1016/s0092-8674(00)80604-2
[46]
Deshpande "PHC3, a component of the hPRC-H complex, associates with 2A7E during G0 and is lost in osteosarcoma tumors" Oncogene (2007) 10.1038/sj.onc.1209988
[47]
Ohkumo "Deficiency of the Caenorhabditis elegans DNA polymerase eta homologue increases sensitivity to UV radiation during germ-line development" Cell Struct. Funct. (2006) 10.1247/csf.31.29
[48]
Bürglin, T.R. (2011). Homeodomain Subtypes and Functional Diversity, Springer. 10.1007/978-90-481-9069-0_5
[49]
The Hippo signaling pathway in stem cell biology and cancer

Jung‐Soon Mo, Hyun Woo Park, Kun‐Liang Guan

EMBO reports 2014 10.15252/embr.201438638
[50]
Hers "Akt signalling in health and disease" Cell. Signal. (2011) 10.1016/j.cellsig.2011.05.004

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Published
Jun 14, 2019
Vol/Issue
20(12)
Pages
2912
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Funding
State project “Improving the programs of assisted reproductive technologies when applying innovative high-tech techniques (embryological, cellular, immunological, molecular genetic) Award: AAAA-A18-118053190022-8
Cite This Article
Angelika V. Timofeeva, Vitaliy V. Chagovets, Yulia S. Drapkina, et al. (2019). Cell-Free, Embryo-Specific sncRNA as a Molecular Biological Bridge between Patient Fertility and IVF Efficiency. International Journal of Molecular Sciences, 20(12), 2912. https://doi.org/10.3390/ijms20122912
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