Transcriptomic profile of genes encoding proteins responsible for regulation of cells differentiation and neurogenesis in vivo and in vitro – an oocyte model approach

Lisa Moncrieff; Ievgeniia Kocherova; Artur Bryja; Wiesława Kranc; Joanna Perek; Magdalena Kulus; Michal Jeseta; Claudia Dompe; Greg Hutchings; Krzysztof Janowicz; Piotr Celichowski; Małgorzata Bruska; Maciej Zabel; Bartosz Kempisty; Paul Mozdziak

doi:10.2478/acb-2020-0001

Abstract

The growth and development of the oocyte is essential for the ovarian follicle. Cumulus cells (CCs) - a population of granulosa cells - exchange metabolites, proteins and oocyte-derived paracrine factors with the oocyte through gap junctions, to contribute to the competency and health of the oocyte. This bi-directional communication of the cumulus-oocyte complex could be better understood through the micro-analysis of a porcine oocyte gene expression before in vitro maturation (IVM) and after. Additionally, the study of the somatic and gamete cells differentiation capability into neuronal lineage would be promising for future stem cell research as granulosa cells are easily accessible waste material from in vitro fertilization (IVF) procedures. Therefore, in this study, the oocytes of 45 pubertal Landrace gilts were isolated and the protein expression of the COCs were analyzed through micro-analysis techniques. Genes belonging to two ontological groups: neuron differentiation and negative regulation of cell differentiation have been identified which have roles in proliferation, migration and differentiation. Twenty identified porcine oocyte genes (VEGFA, BTG2, MCOLN3, EGR2, TGFBR3, GJA1, FST, CTNNA2, RTN4, MDGA1, KIT, RYK, NOTCH2, RORA, SMAD4, ITGB1, SEMA5A, SMARCA1, WWTR1 and APP) were found to be down-regulated after the transition of IVM compared to in vitro. These results could be applied as gene markers for the proliferation, migration and differentiation occurring in the bi-directional communication between the oocyte and CCs.

Running title: Differentiation and neurogenesis in oocyte cells

References

Gosden R, Lee B. Portrait of an oocyte: Our obscure origin. J Clin Invest. 2010;120:973–83; DOI:10.1172/JCI41294.
Open DOI Search in Google Scholar Back to article
Kranc W, Chachuła A, Bryja A, Ciesiołka S, Budna J, Wojtanowicz-Mark-iewicz K, Sumelka E, Borys S, Antosik P, Bukowska D, Bruska M, Nowicki M, Kempisty B. Selected molecular and physiological aspects of mammalian ovarian granulosa cells in primary culture. Med Weter. 2016;72:723–7; DOI:10.21521/mw.5606.
Open DOI Search in Google Scholar Back to article
Yuan YQ, Van Soom A, Leroy JLMR, Dewulf J, Van Zeveren A, De Kruif A, Peelman LJ. Apoptosis in cumulus cells, but not in oocytes, may influence bovine embryonic developmental competence. Theriogenology. 2005;63:2147–63; DOI:10.1016/j.theriogenology.2004.09.054.
Open DOI Search in Google Scholar Back to article
Russell DL, Gilchrist RB, Brown HM, Thompson JG. Bidirectional communication between cumulus cells and the oocyte: Old hands and new players? Theriogenology. 2016;86:62–8; DOI:10.1016/j. theriogenology.2016.04.019.
Open DOI Search in Google Scholar Back to article
Zhai Y, Yao G, Rao F, Wang Y, Song X, Sun F. Excessive nerve growth factor impairs bidirectional communication between the oocyte and cumulus cells resulting in reduced oocyte competence. Reprod Biol Endocrinol. 2018;16:1–11; DOI:10.1186/s12958-018-0349-7.
Open DOI Search in Google Scholar Back to article
Hoheisel JD. Microarray technology: Beyond transcript profiling and genotype analysis. Nat Rev Genet. 2006;7:200–10; DOI:10.1038/nrg1809.
Open DOI Search in Google Scholar Back to article
Kossowska-Tomaszczuk K, De Geyter C, De Geyter M, Martin I, Holzgreve W, Scherberich A, Zhang H. The multipotency of luteinizing granulosa cells collected from mature ovarian follicles. Stem Cells. 2009;27:210–9; DOI:10.1634/stemcells.2008-0233.
Open DOI Search in Google Scholar Back to article
Shimada M. Cumulus Oocyte Complex: Cumulus Cells Regulate Oocyte Growth and Maturation. J Mamm Ova Res. 2009;26:189–94; DOI:10.1274/jmor.26.189.
Open DOI Search in Google Scholar Back to article
Chermuła B, Brazert M, Jeseta M, Ożegowska K, Sujka-Kordowska P, Konwerska A, Bryja A, Kranc W, Jankowski M, Nawrocki MJ, Kocherova I, Celichowski P, Borowiec B, Popis M, Budna-Tukan J, Antosik P, Bukowska D, Brussow KP, Pawelczyk L, Bruska M, Zabel M, Nowicki M, Kempisty B. The unique mechanisms of cellular proliferation, migration and apoptosis are regulated through oocyte maturational development—A complete transcriptomic and histochemical study. Int J Mol Sci. 2019;20; DOI:10.3390/ijms20010084.
Open DOI Search in Google Scholar Back to article
Rybska M, Knap S, Jankowski M, Jeseta M, Bukowska D, Antosik P, Nowicki M, Zabel M, Kempisty B, Jaśkowski JM. Characteristic of factors influencing the proper course of folliculogenesis in mammals. Med J Cell Biol. 2018;6:33–8; DOI:10.2478/acb-2018-0006.
Open DOI Search in Google Scholar Back to article
Moncrieff L, Mozdziak P, Jeseta M, Machatkova M, Kranc W, Kempisty B. Ovarian follicular cells - Living in the shadow of stemness cellular competence. Med J Cell Biol. 2019;7:134–40; DOI:10.2478/acb-2019-0018.
Open DOI Search in Google Scholar Back to article
Zeng H, Qin L, Zhao D, Tan X, Manseau EJ, Mien VH, Senger DR, Brown LF, Nagy JA, Dvorak HF. Orphan nuclear receptor TR3/Nur77 regulates VEGF-A-induced angiogenesis through its transcriptional activity. J Exp Med. 2006;203:719–29; DOI:10.1084/jem.20051523.
Open DOI Search in Google Scholar Back to article
Gao X, Zhang J, Pan Z, Li Q, Liu H. The distribution and expression of vascular endothelial growth factor A (VEGFA) during follicular development and atresia in the pig. Reprod Fertil Dev. 2020;32:259; DOI:10.1071/RD18508.
Open DOI Search in Google Scholar Back to article
Farioli-Vecchioli S, Micheli L, Ceccarelli M, Leonardi L, Tirone F. Genetic control of adult neurogenesis: Interplay of differentiation, proliferation and survival modulates new neurons function and memory circuits. Front Cell Neurosci. 2013; DOI:10.3389/fncel.2013.00059.
Open DOI Search in Google Scholar Back to article
Li F, Liu J, Park ES, Jo M, Curry TE. The B cell translocation gene (BTG) family in the rat ovary: Hormonal induction, regulation, and impact on cell cycle kinetics. Endocrinology. 2009;150:3894–902; DOI:10.1210/en.2008-1650.
Open DOI Search in Google Scholar Back to article
Martina JA, Lelouvier B, Puertollano R. The Calcium Channel Mucolipin-3 is a Novel Regulator of Trafficking Along the Endosomal Pathway. Traffic. 2009;10:1143–56; DOI:10.1111/j.1600-0854.2009.00935.x.
Open DOI Search in Google Scholar Back to article
Martina JA, Lelouvier B, Puertollano R. The calcium channel mucolipin-3 is a novel regulator of trafficking along the endosomal pathway. Traffic. 2009;10:1143–56; DOI:10.1111/j.1600-0854.2009.00935.x.
Open DOI Search in Google Scholar Back to article
Kulus M, Sujka-kordowska P, Konwerska A, Celichowski P, Kranc W, Kulus J, Piotrowska-kempisty H, Antosik P. New Molecular Markers Involved in Regulation of Ovarian Granulosa Cell Morphogenesis , Development and Di ff erentiation during Short-Term Primary In vitro Culture — Transcriptomic and Histochemical Study Based on Ovaries and Individual Separated Follicle. Int J Mol Sci. 2019;20:3966; DOI:doi:10.3390/ijms20163966.
Open DOI Search in Google Scholar Back to article
LeBlanc SE, Srinivasan R, Ferri C, Mager GM, Gillian-Daniel AL, Wrabetz L, Svaren J. Regulation of cholesterol/lipid biosynthetic genes by Egr2/Krox20 during peripheral nerve myelination. J Neurochem. 2005;93:737–48; DOI:10.1111/j.1471-4159.2005.03056.x.
Open DOI Search in Google Scholar Back to article
Jang S-W, LeBlanc SE, Roopra A, Wrabetz L, Svaren J. In vitro detection of Egr2 binding to target genes during peripheral nerve myelination. J Neurochem. 2006;98:1678–87; DOI:10.1111/j.1471-4159.2006.04069.x.
Open DOI Search in Google Scholar Back to article
Topilko P, Schneider-Maunoury S, Levi G, Baron-Van Evercooren A, Chennoufi ABY, Seitanidou T, Babinet C, Charnay P. Krox-20 controls myelination in the peripheral nervous system. Nature. 1994;371:796–9; DOI:10.1038/371796a0.
Open DOI Search in Google Scholar Back to article
Jin H, Won M, Shin E, Kim HM, Lee K, Bae J. EGR2 is a gonadotropin-in-duced survival factor that controls the expression of IER3 in ovarian granulosa cells. Biochem Biophys Res Commun. 2017;482:877–82; DOI:10.1016/j.bbrc.2016.11.127.
Open DOI Search in Google Scholar Back to article
Brązert M, Kranc W, Nawrocki MJ, Sujka–Kordowska P, Konwerska A, Jankowski M, Kocherova I, Celichowski P, Jeseta M, Ożegowska K, Antosik P, Bukowska D, Skowroński MT, Bruska M, Pawelczyk L, Zabel M, Piotrowska–Kempisty H, Nowicki M, Kempisty B. New markers for regulation of transcription and macromolecule metabolic process in porcine oocytes during in vitro maturation. Mol Med Rep. 2020;21:1537–51; DOI:10.3892/mmr.2020.10963.
Open DOI Search in Google Scholar Back to article
Stenvers KL, Tursky ML, Harder KW, Kountouri N, Amatayakul-Chantler S, Grail D, Small C, Weinberg RA, Sizeland AM, Zhu H-J. Heart and Liver Defects and Reduced Transforming Growth Factor 2 Sensitivity in Transforming Growth Factor Type III Receptor-Deficient Embryos. Mol Cell Biol. 2003;23:4371–85; DOI:10.1128/mcb.23.12.4371-4385.2003.
Open DOI Search in Google Scholar Back to article
Kranc W, Budna J, Chachuła A, Borys S, Bryja A, Rybska M, Ciesiółka S, Sumelka E, Jeseta M, Brüssow KP, Bukowska D, Antosik P, Bruska M, Nowicki M, Zabel M, Kempisty B. Cell Migration Is the Ontology Group Differentially Expressed in Porcine Oocytes before and after in vitro Maturation: A Microarray Approach. DNA Cell Biol. 2017;36:273–82; DOI:10.1089/dna.2016.3425.
Open DOI Search in Google Scholar Back to article
Fu Y, Zhang S-S, Xiao S, Basheer WA, Baum R, Epifantseva I, Hong T, Shaw RM. Cx43 Isoform GJA1-20k Promotes Microtubule Dependent Mitochondrial Transport. Front Physiol. 2017;8:905; DOI:10.3389/fphys.2017.00905.
Open DOI Search in Google Scholar Back to article
Santiago MF, Alcami P, Striedinger KM, Spray DC, Scemes E. The carboxyl-terminal domain of Connexin43 is a negative modulator of neuronal differentiation. J Biol Chem. 2010;285:11836–45; DOI:10.1074/jbc. M109.058750.
Open DOI Search in Google Scholar Back to article
Involvement of GJA1 and Gap Junctional Intercellular Communication between Cumulus Cells and Oocytes from Women with PCOS n.d.https://www.hindawi.com/journals/bmri/2020/5403904/ (accessed March 10, 2020).
Search in Google Scholar Back to article
Ying SY, Becker A, Swanson G, Tan P, Ling N, Esch F, Ueno N, Shimasaki S, Guillemin R. Follistatin specifically inhibits pituitary follicle stimulating hormone release invitro. Biochem Biophys Res Commun. 1987;149:133–9; DOI:10.1016/0006-291X(87)91614-7.
Open DOI Search in Google Scholar Back to article
Nakamura T, Hasegawa Y, Sugino K, Kogawa K, Titani K, Sugino H. Follistatin inhibits activin-induced differentiation of rat follicular granulosa cells in vitro. BBA - Mol Cell Res. 1992;1135:103–9; DOI:10.1016/0167-4889(92)90173-9.
Open DOI Search in Google Scholar Back to article
Dragovic RA, Ritter LJ, Schulz SJ, Amato F, Thompson JG, Armstrong DT, Gilchrist RB. Oocyte-Secreted Factor Activation of SMAD 2/3 Signaling Enables Initiation of Mouse Cumulus Cell Expansion1. Biol Reprod. 2007;76:848–57; DOI:10.1095/biolreprod.106.057471.
Open DOI Search in Google Scholar Back to article
Ashry M, Lee K, Mondal M, Datta TK, Folger JK, Rajput SK, Zhang K, Hemeida NA, Smith GW. Expression of TGFβ superfamily components and other markers of oocyte quality in oocytes selected by brilliant cresyl blue staining: Relevance to early embryonic development. Mol Reprod Dev. 2015;82:251–64; DOI:10.1002/mrd.22468.
Open DOI Search in Google Scholar Back to article
Guo Z, Islam MS, Liu D, Liu G, Lv L, Yang Y, Fu B, Wang L, Liu Z, He H, Wu H. Differential effects of follistatin on porcine oocyte competence and cumulus cell gene expression in vitro. Reprod Domest Anim. 2018;53:3–10; DOI:10.1111/rda.13035.
Open DOI Search in Google Scholar Back to article
Terracciano A, Esko T, Sutin AR, De Moor MHM, Meirelles O, Zhu G, Tanaka T, Giegling I, Nutile T, Realo A, Allik J, Hansell NK, Wright MJ, Montgomery GW, Willemsen G, Hottenga JJ, Friedl M, Ruggiero D, Sorice R, Sanna S, Cannas A, Räikkönen K, Widen E, Palotie A, Eriksson JG, Cucca F, Krueger RF, Lahti J, Luciano M, Smoller JW, Van Duijn CM, Abecasis GR, Boomsma DI, Ciullo M, Costa PT, Ferrucci L, Martin NG, Metspalu A, Rujescu D, Schlessinger D, Uda M. Meta-analysis of genome-wide association studies identifies common variants in CTNNA2 associated with excitement-seeking. Transl Psychiatry. 2011;1:e49–e49; DOI:10.1038/tp.2011.42.
Open DOI Search in Google Scholar Back to article
Schaffer AE, Breuss MW, Caglayan AO, Al-Sanaa N, Al-Abdulwahed HY, Kaymakçalan H, Yılmaz C, Zaki MS, Rosti RO, Copeland B, Baek ST, Musaev D, Scott EC, Ben-Omran T, Kariminejad A, Kayserili H, Mojahedi F, Kara M, Cai N, Silhavy JL, Elsharif S, Fenercioglu E, Barshop BA, Kara B, Wang R, Stanley V, James KN, Nachnani R, Kalur A, Megahed H, Incecik F, Danda S, Alanay Y, Faqeih E, Melikishvili G, Mansour L, Miller I, Sukhudyan B, Chelly J, Dobyns WB, Bilguvar K, Jamra RA, Gunel M, Gleeson JG. Biallelic loss of human CTNNA2, encoding αN-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration. Nat Genet. 2018;50:1093–101; DOI:10.1038/s41588-018-0166-0.
Open DOI Search in Google Scholar Back to article
Budna J, Celichowski P, Bryja A, Dyszkiewicz-Konwińska M, Jeseta M, Bukowska D, Antosik P, Brüssow KP, Bruska M, Nowicki M, Zabel M, Kempisty B. Significant down-regulation of “biological adhesion” genes in porcine oocytes after IVM. Int J Mol Sci. 2017;18:2685; DOI:10.3390/ijms18122685.
Open DOI Search in Google Scholar Back to article
Chi C, Liu N, Yue L, Qi W-W, Xu L-L, Qiu W-S. RTN4/Nogo is an independent prognostic marker for gastric cancer: preliminary results. Eur Rev Med Pharmacol Sci. 2015;19:241–6.
Search in Google Scholar Back to article
Teng FYH, Tang BL. Nogo/RTN4 isoforms and RTN3 expression protect SH-SY5Y cells against multiple death insults. Mol Cell Biochem. 2013;384:7–19; DOI:10.1007/s11010-013-1776-6.
Open DOI Search in Google Scholar Back to article
Kranc W, Budna J, Chachuła A, Borys S, Bryja A, Rybska M, Ciesiółka S, Sumelka E, Jeseta M, Brüssow KP, Bukowska D, Antosik P, Bruska M, Nowicki M, Zabel M, Kempisty B. “Cell Migration” Is the Ontology Group Differentially Expressed in Porcine Oocytes Before and After In vitro Maturation: A Microarray Approach. DNA Cell Biol. 2017;36:273–82; DOI:10.1089/dna.2016.3425.
Open DOI Search in Google Scholar Back to article
Takeuchi A, O’Leary DDM. Radial migration of superficial layer cortical neurons controlled by novel Ig cell adhesion molecule MDGA1. J Neurosci. 2006;26:4460–4; DOI:10.1523/JNEUROSCI.4935-05.2006.
Open DOI Search in Google Scholar Back to article
Kähler AK, Djurovic S, Kulle B, Jönsson EG, Agartz I, Hall H, Opjordsmoen S, Jakobsen KD, Hansen T, Melle I, Werge T, Steen VM, Andreassen OA. Association analysis of schizophrenia on 18 genes involved in neuronal migration: MDGA1 as a new susceptibility gene. Am J Med Genet Part B Neuropsychiatr Genet. 2008;147:1089–100; DOI:10.1002/ajmg.b.30726.
Open DOI Search in Google Scholar Back to article
Driancourt MA, Reynaud K, Cortvrindt R, Smitz J. Roles of KIT and KIT LIGAND in ovarian function. Rev Reprod. 2000;5:143–52; DOI:10.1530/ror.0.0050143.
Open DOI Search in Google Scholar Back to article
Conde P, Morado S, Alvarez G, Smitz J, Gentile T, Cetica P. Effect of the hematopoietic growth factors erythropoietin and kit ligand on bovine oocyte in vitro maturation and developmental competence. Theriogenology. 2019;123:37–44; DOI:10.1016/j.theriogenology.2018.09.014.
Open DOI Search in Google Scholar Back to article
Xu B, Zhang YW, Tong XH, Liu YS. Characterization of microRNA profile in human cumulus granulosa cells: Identification of microRNAs that regulate Notch signaling and are associated with PCOS. Mol Cell Endocrinol. 2015;404:26–36; DOI:10.1016/j.mce.2015.01.030.
Open DOI Search in Google Scholar Back to article
Sun T, Diaz FJ. Ovulatory signals alter granulosa cell behavior through YAP1 signaling. Reprod Biol Endocrinol. 2019;17:1–14; DOI:10.1186/s12958-019-0552-1.
Open DOI Search in Google Scholar Back to article
Chang WH, Choi SH, Moon BS, Cai M, Lyu J, Bai J, Gao F, Hajjali I, Zhao Z, Campbell DB, Weiner LP, Lu W. Smek1/2 is a nuclear chaperone and cofactor for cleaved Wnt receptor Ryk, regulating cortical neurogenesis. Proc Natl Acad Sci U S A. 2017;114:E10717–25; DOI:10.1073/pnas.1715772114.
Open DOI Search in Google Scholar Back to article
Budna J, Bryja A, Celichowski P, Kahan R, Kranc W, Ciesiółka S, Rybska M, Borys S, Jeseta M, Bukowska D, Antosik P, Brüssow KP, Bruska M, Nowicki M, Zabel M, Kempisty B. Genes of cellular components of morphogenesis in porcine oocytes before and after IVM. Reproduction. 2017;154:535–45; DOI:10.1530/REP-17-0367.
Open DOI Search in Google Scholar Back to article
Kranc W, Celichowski P, Budna J, Khozmi R, Bryja A, Ciesiółka S, Rybska M, Borys S, Jeseta M, Bukowska D, Antosik P, Brüssow KP, Bruska M, Nowicki M, Zabel M, Kempisty B. Positive regulation of macromolecule metabolic process belongs to the main mechanisms crucial for porcine oocytes maturation. Adv Cell Biol. 2017;5:15–31; DOI:10.1515/acb-2017-0002.
Open DOI Search in Google Scholar Back to article
Kawaguchi-Niida M, Shibata N, Furuta Y. Smad4 is essential for directional progression from committed neural progenitor cells through neuronal differentiation in the postnatal mouse brain. Mol Cell Neurosci. 2017;83:55–64; DOI:10.1016/j.mcn.2017.06.008.
Open DOI Search in Google Scholar Back to article
Xing N, Liang Y, Gao Z, He J, He X, Li H, Dong C. Expression and localization of Smad2 and Smad4 proteins in the porcine ovary. Acta Histochem. 2014;116:1301–6; DOI:10.1016/j.acthis.2014.07.014.
Open DOI Search in Google Scholar Back to article
Goldberg JL, Vargas ME, Wang JT, Mandemakers W, Oster SF, Sretavan DW, Barres BA. An oligodendrocyte lineage-specific semaphorin, sema5A, inhibits axon growth by retinal ganglion cells. J Neurosci. 2004;24:4989–99; DOI:10.1523/JNEUROSCI.4390-03.2004.
Open DOI Search in Google Scholar Back to article
Nawrocki M, Celichowski P, Budna J, Bryja A, Kranc W, Ciesiółka S, Borys S, Knap S, Jeseta M, Khozmii R, Bukowska D, Antosik P, Brussow KP, Bruska M, Nowicki M, Zabel M, Kempisty B. The blood vessels development, morphogenesis and blood circulation are three ontologic groups highly up-regulated in porcine oocytes before in vitro. Med J Cell Biol. 2017;5:135–142; DOI:10.1515/acb-2017-0012.
Open DOI Search in Google Scholar Back to article
Goodwin LR, Picketts DJ. The role of ISWI chromatin remodeling complexes in brain development and neurodevelopmental disorders. Mol Cell Neurosci. 2018;87:55–64; DOI:10.1016/j.mcn.2017.10.008.
Open DOI Search in Google Scholar Back to article
Bergström P, Agholme L, Nazir FH, Satir TM, Toombs J, Wellington H, Strandberg J, Bontell TO, Kvartsberg H, Holmström M, Boreström C, Simonsson S, Kunath T, Lindahl A, Blennow K, Hanse E, Portelius E, Wray S, Zetterberg H. Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation. Sci Rep. 2016;6:1–14; DOI:10.1038/srep29200.
Open DOI Search in Google Scholar Back to article

Transcriptomic profile of genes encoding proteins responsible for regulation of cells differentiation and neurogenesis in vivo and in vitro – an oocyte model approach

Abstract

Paradigm

My account