Browse > Article
http://dx.doi.org/10.5653/cerm.2019.46.2.76

Differential gene expression analysis of human cumulus cells  

Demiray, Sirin Bakti (Assisted Reproduction Unit, Tepecik Education and Research Hospital)
Goker, Ege Nazan Tavmergen (Department of Obstetrics and Gynecology, Ege University Faculty of Medicine)
Tavmergen, Erol (Department of Obstetrics and Gynecology, Ege University Faculty of Medicine)
Yilmaz, Ozlem (Department of Histology and Embryology, Ege University Faculty of Medicine)
Calimlioglu, Nilufer (Department of Obstetrics and Gynecology, Ege University Faculty of Medicine)
Soykam, Huseyin Okan (Epigenetiks Genetics Bioinformatics Software Inc.)
Oktem, Gulperi (Department of Histology and Embryology, Ege University Faculty of Medicine)
Sezerman, Ugur (Department of Biostatistics and Bioinformatics, Acibadem Mehmet Ali Aydinlar University, Institute of Health Sciences)
Publication Information
Clinical and Experimental Reproductive Medicine / v.46, no.2, 2019 , pp. 76-86 More about this Journal
Abstract
Objective: This study was performed to explore the possibility that each oocyte and its surrounding cumulus cells might have different genetic expression patterns that could affect human reproduction. Methods: Differential gene expression analysis was performed for 10 clusters of cumulus cells obtained from 10 cumulus-oocyte complexes from 10 patients. Same procedures related to oocyte maturation, microinjection, and microarray analyses were performed for each group of cumulus cells. Two differential gene expression analyses were performed: one for the outcome of clinical pregnancy and one for the outcome of live birth. Results: Significant genes resulting from these analyses were selected and the top 20 affected pathways in each group were analyzed. Circadian entrainment is determined to be the most affected pathway for clinical pregnancy, and proteoglycans in cancer pathway is the most affected pathway for live birth. Circadian entrainment is also amongst the 12 pathways that are found to be in top 20 affected pathways for both outcomes, and has both lowest p-value and highest number of times found count. Conclusion: Although further confirmatory studies are necessary, findings of this study suggest that these pathways, especially circadian entrainment in cumulus cells, may be essential for embryo development and pregnancy.
Keywords
Assisted reproductive techniques; Circadian clocks; Cumulus cells; Granulosa cells; Infertility; Live birth; Microarray analysis; Ovarian follicle; Pregnancy; Proteoglycans;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Ideker T, Ozier O, Schwikowski B, Siegel AF. Discovering regulatory and signalling circuits in molecular interaction networks. Bioinformatics 2002;18 Suppl 1:S233-40.   DOI
2 Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, et al. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 2009;25:1091-3.   DOI
3 Kanehisa M, Goto S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res 2000;28:27-30.   DOI
4 Sellix MT, Menaker M. Circadian clocks in mammalian reproductive physiology: effects of the "other" biological clock on fertility. Discov Med 2011;11:273-81.
5 Reiter RJ, Tan DX, Korkmaz A, Rosales-Corral SA. Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology. Hum Reprod Update 2014;20:293-307.   DOI
6 Burnik Papler T, Vrtacnik Bokal E, Maver A, Kopitar AN, Lovrecic L. Transcriptomic analysis and meta-analysis of human granulosa and cumulus cells. PLoS One 2015;10:e0136473.   DOI
7 Huo LJ, Fan HY, Zhong ZS, Chen DY, Schatten H, Sun QY. Ubiquitin- proteasome pathway modulates mouse oocyte meiotic maturation and fertilization via regulation of MAPK cascade and cyclin B1 degradation. Mech Dev 2004;121:1275-87.   DOI
8 Yi YJ, Nagyova E, Manandhar G, Prochazka R, Sutovsky M, Park CS, et al. Proteolytic activity of the 26S proteasome is required for the meiotic resumption, germinal vesicle breakdown, and cumulus expansion of porcine cumulus-oocyte complexes matured in vitro. Biol Reprod 2008;78:115-26.   DOI
9 Wayne CM, Fan HY, Cheng X, Richards JS. Follicle-stimulating hormone induces multiple signaling cascades: evidence that activation of Rous sarcoma oncogene, RAS, and the epidermal growth factor receptor are critical for granulosa cell differentiation. Mol Endocrinol 2007;21:1940-57.   DOI
10 Assidi M, Montag M, Van der Ven K, Sirard MA. Biomarkers of human oocyte developmental competence expressed in cumulus cells before ICSI: a preliminary study. J Assist Reprod Genet 2011;28:173-88.   DOI
11 Balasch J. Investigation of the infertile couple: investigation of the infertile couple in the era of assisted reproductive technology: a time for reappraisal. Hum Reprod 2000;15:2251-7.   DOI
12 Cillo F, Brevini TA, Antonini S, Paffoni A, Ragni G, Gandolfi F. Association between human oocyte developmental competence and expression levels of some cumulus genes. Reproduction 2007;134:645-50.   DOI
13 Bettegowda A, Patel OV, Lee KB, Park KE, Salem M, Yao J, et al. Identification of novel bovine cumulus cell molecular markers predictive of oocyte competence: functional and diagnostic implications. Biol Reprod 2008;79:301-9.   DOI
14 Matzuk MM, Burns KH, Viveiros MM, Eppig JJ. Intercellular communication in the mammalian ovary: oocytes carry the conversation. Science 2002;296:2178-80.   DOI
15 True L, Feng Z. Immunohistochemical validation of expression microarray results. J Mol Diagn 2005;7:149-51.   DOI
16 Chen Y, Kong S, Tang X, Fu Y, Wang B, Zhang S, et al. Preimplantation mouse embryo is a target for opioid ligand-receptor signaling. Biol Reprod 2014;91:4.   DOI
17 Fenwick J, Platteau P, Murdoch AP, Herbert M. Time from insemination to first cleavage predicts developmental competence of human preimplantation embryos in vitro. Hum Reprod 2002;17:407-12.   DOI
18 Feuerstein P, Cadoret V, Dalbies-Tran R, Guerif F, Bidault R, Royere D. Gene expression in human cumulus cells: one approach to oocyte competence. Hum Reprod 2007;22:3069-77.   DOI
19 Gloaguen P, Crepieux P, Heitzler D, Poupon A, Reiter E. Mapping the follicle-stimulating hormone-induced signaling networks. Front Endocrinol (Lausanne) 2011;2:45.   DOI
20 Fan HY, Liu Z, Mullany LK, Richards JS. Consequences of RAS and MAPK activation in the ovary: the good, the bad and the ugly. Mol Cell Endocrinol 2012;356:74-9.   DOI
21 Yu J, Poulton J, Huang YC, Deng WM. The hippo pathway promotes Notch signaling in regulation of cell differentiation, proliferation, and oocyte polarity. PLoS One 2008;3:e1761.   DOI
22 Chen H, Kui C, Chan HC. Ca(2+) mobilization in cumulus cells: role in oocyte maturation and acrosome reaction. Cell Calcium 2013;53:68-75.   DOI
23 Sanford JC, Batten BE. Endocytosis of follicle-stimulating hormone by ovarian granulosa cells: analysis of hormone processing and receptor dynamics. J Cell Physiol 1989;138:154-64.   DOI
24 Devjak R, Fon Tacer K, Juvan P, Virant Klun I, Rozman D, Vrtacnik Bokal E. Cumulus cells gene expression profiling in terms of oocyte maturity in controlled ovarian hyperstimulation using GnRH agonist or GnRH antagonist. PLoS One 2012;7:e47106.   DOI
25 Watanabe M, Fukuda A, Nabekura J. The role of GABA in the regulation of GnRH neurons. Front Neurosci 2014;8:387.
26 Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 2015;43:e47.   DOI
27 della Ragione T, Verheyen G, Papanikolaou EG, Van Landuyt L, Devroey P, Van Steirteghem A. Developmental stage on day-5 and fragmentation rate on day-3 can influence the implantation potential of top-quality blastocysts in IVF cycles with single embryo transfer. Reprod Biol Endocrinol 2007;5:2.   DOI
28 van Montfoort AP, Geraedts JP, Dumoulin JC, Stassen AP, Evers JL, Ayoubi TA. Differential gene expression in cumulus cells as a prognostic indicator of embryo viability: a microarray analysis. Mol Hum Reprod 2008;14:157-68.   DOI
29 Carvalho BS, Irizarry RA. A framework for oligonucleotide microarray preprocessing. Bioinformatics 2010;26:2363-7.   DOI
30 Bakir-Gungor B, Egemen E, Sezerman OU. PANOGA: a web server for identification of SNP-targeted pathways from genomewide association study data. Bioinformatics 2014;30:1287-9.   DOI
31 Stark C, Breitkreutz BJ, Reguly T, Boucher L, Breitkreutz A, Tyers M. BioGRID: a general repository for interaction datasets. Nucleic Acids Res 2006;34:D535-9.   DOI
32 Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003;13:2498-504.   DOI
33 Murdoch WJ, Lund SA. Prostaglandin-independent anovulatory mechanism of indomethacin action: inhibition of tumor necrosis factor alpha-induced sheep ovarian cell apoptosis. Biol Reprod 1999;61:1655-9.   DOI
34 Huang X, Hao C, Shen X, Liu X, Shan Y, Zhang Y, et al. Differences in the transcriptional profiles of human cumulus cells isolated from MI and MII oocytes of patients with polycystic ovary syndrome. Reproduction 2013;145:597-608.   DOI
35 Luan X, Liu D, Cao Z, Luo L, Liu M, Gao M, et al. Transcriptome profiling identifies differentially expressed genes in Huoyan goose ovaries between the laying period and ceased period. PLoS One 2014;9:e113211.   DOI
36 Salustri A, Camaioni A, Di Giacomo M, Fulop C, Hascall VC. Hyaluronan and proteoglycans in ovarian follicles. Hum Reprod Update 1999;5:293-301.   DOI
37 Tiwari M, Prasad S, Tripathi A, Pandey AN, Ali I, Singh AK, et al. Apoptosis in mammalian oocytes: a review. Apoptosis 2015;20:1019-25.   DOI
38 Hennebold JD. Preventing granulosa cell apoptosis through the action of a single microRNA. Biol Reprod 2010;83:165-7.   DOI
39 Peter AT, Dhanasekaran N. Apoptosis of granulosa cells: a review on the role of MAPK-signalling modules. Reprod Domest Anim 2003;38:209-13.   DOI
40 Su YQ, Denegre JM, Wigglesworth K, Pendola FL, O'Brien MJ, Eppig JJ. Oocyte-dependent activation of mitogen-activated protein kinase (ERK1/2) in cumulus cells is required for the maturation of the mouse oocyte-cumulus cell complex. Dev Biol 2003;263:126-38.   DOI
41 El-Talatini MR, Taylor AH, Elson JC, Brown L, Davidson AC, Konje JC. Localisation and function of the endocannabinoid system in the human ovary. PLoS One 2009;4:e4579.   DOI
42 Vigone G, Merico V, Prigione A, Mulas F, Sacchi L, Gabetta M, et al. Transcriptome based identification of mouse cumulus cell markers that predict the developmental competence of their enclosed antral oocytes. BMC Genomics 2013;14:380.   DOI
43 Battista N, Meccariello R, Cobellis G, Fasano S, Di Tommaso M, Pirazzi V, et al. The role of endocannabinoids in gonadal function and fertility along the evolutionary axis. Mol Cell Endocrinol 2012;355:1-14.   DOI
44 McGinnis LK, Kinsey WH. Role of focal adhesion kinase in oocytefollicle communication. Mol Reprod Dev 2015;82:90-102.   DOI
45 Yodoi R, Tamba S, Morimoto K, Segi-Nishida E, Nishihara M, Ichikawa A, et al. RhoA/Rho kinase signaling in the cumulus mediates extracellular matrix assembly. Endocrinology 2009;150:3345-52.   DOI
46 Ikeda S, Yamada M. Midkine and cytoplasmic maturation of mammalian oocytes in the context of ovarian follicle physiology. Br J Pharmacol 2014;171:827-36.   DOI
47 Erickson GF, Shimasaki S. The spatiotemporal expression pattern of the bone morphogenetic protein family in rat ovary cell types during the estrous cycle. Reprod Biol Endocrinol 2003;1:9.   DOI
48 Knight PG, Glister C. TGF-beta superfamily members and ovarian follicle development. Reproduction 2006;132:191-206.   DOI
49 Demiray SB, Yilmaz O, Goker EN, Tavmergen E, Calimlioglu N, Sezerman U, et al. Expression of the bone morphogenetic protein-2 (BMP2) in the human cumulus cells as a biomarker of oocytes and embryo quality. J Hum Reprod Sci 2017;10:194-200.   DOI
50 Hamel M, Dufort I, Robert C, Leveille MC, Leader A, Sirard MA. Identification of follicular marker genes as pregnancy predictors for human IVF: new evidence for the involvement of luteinization process. Mol Hum Reprod 2010;16:548-56.   DOI