Expression profiling and function analysis identified new genes regulating cumulus expansion and cumulus cell apoptosis in mouse oocytes

in Reproduction
Authors:
Min Zhang College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an City, P. R. China

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Jia-Shun Wu College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an City, P. R. China

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Xiao Han College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an City, P. R. China

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Rui-Jie Ma College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an City, P. R. China

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Jia-Li Xu College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an City, P. R. China

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Ming-Tao Xu College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an City, P. R. China

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Hong-Jie Yuan College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an City, P. R. China

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Ming-Jiu Luo College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an City, P. R. China

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Jing-He Tan College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an City, P. R. China

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https://orcid.org/0000-0001-6437-6259

Correspondence should be addressed to J-H Tan; Email: tanjh@sdau.edu.cn
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In brief

Genes expressed in cumulus cells might be used as markers for competent oocytes/embryos. This study identified and validated a new group of cumulus expansion and/or apoptosis-regulating genes, which may be used for selection of quality oocytes/embryos.

Abstract

Studies on the mechanisms behind cumulus expansion and cumulus cell (CC) apoptosis are essential for understanding the mechanisms for oocyte maturation. Genes expressed in CCs might be used as markers for competent oocytes and/or embryos. In this study, both in vitro (IVT) and in vivo (IVO) mouse oocyte models with significant difference in cumulus expansion and CC apoptosis were used to identify and validate new genes regulating cumulus expansion and CC apoptosis of mouse oocytes. We first performed mRNA sequencing and bioinformatic analysis using the IVT oocyte model to identify candidate genes. We then analyzed functions of the candidate genes by RNAi or gene overexpression to select the candidate cumulus expansion and CC apoptosis-regulating genes. Finally, we validated the cumulus expansion and CC apoptosis-regulating genes using the IVO oocyte model. The results showed that while Spp1, Sdc1, Ldlr, Ezr and Mmp2 promoted, Bmp2, Angpt2, Edn1, Itgb8, Cxcl10 and Agt inhibited cumulus expansion. Furthermore, Spp1, Sdc1 and Ldlr inhibited CC apoptosis. In conclusion, by using both IVT and IVO oocyte models, we have identified and validated a new group of cumulus expansion and/or apoptosis-regulating genes, which may be used for selection of quality oocytes/embryos and for elucidating the molecular mechanisms behind oocyte maturation.

 

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  • Aguila L, Treulen F, Therrien J, Felmer R, Valdivia M & & Smith LC 2020 Oocyte selection for in vitro embryo production in bovine species: noninvasive approaches for new challenges of oocyte competence. Animals (Basel) 10. (https://doi.org/10.3390/ani10122196)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Almeida CP, Ferreira MCF, Silveira CO, Campos JR, Borges IT, Baeta PG, Silva FHS, Reis FM & & Del Puerto HL 2018 Clinical correlation of apoptosis in human granulosa cells-A review. Cell Biology International 42 12761281. (https://doi.org/10.1002/cbin.11036)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Aranda G, Fernandez-Ruiz R, Palomo M, Romo M, Mora M, Halperin I, Casals G, Enseñat J, Vidal O, Diaz-Ricart M, et al.2018 Translational evidence of prothrombotic and inflammatory endothelial damage in Cushing syndrome after remission. Clinical Endocrinology 88 415424. (https://doi.org/10.1111/cen.13521)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Assou S, Haouzi D, De Vos J & & Hamamah S 2010 Human cumulus cells as biomarkers for embryo and pregnancy outcomes. Molecular Human Reproduction 16 531538. (https://doi.org/10.1093/molehr/gaq032)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bai L, Chang HM, Cheng JC, Chu G, Leung PCK & & Yang G 2017 ALK2/ALK3-BMPR2/ACVR2A mediate BMP2-induced downregulation of PENTRAXIN 3 expression in human granulosa-lutein cells. Endocrinology 158 35013511. (https://doi.org/10.1210/en.2017-00436)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Barnes FL, Kausche A, Tiglias J, Wood C, Wilton L & & Trounson A 1996 Production of embryos from in vitro-matured primary human oocytes. Fertility and Sterility 65 11511156. (https://doi.org/10.1016/s0015-0282(1658330-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bosco L, Chiarelli R, Roccheri MC, Matranga D & & Ruvolo G 2017 Relationship between apoptosis and survival molecules in human cumulus cells as markers of oocyte competence. Zygote 25 583591. (https://doi.org/10.1017/S0967199417000429)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosa C, Ramirez-Acuña JM, Perez-Romero BA, Guerrero-Rodriguez JF, Martinez-Avila N & & Martinez-Fierro ML 2020 The roles of matrix metalloproteinases and their inhibitors in human diseases. International Journal of Molecular Sciences 21. (https://doi.org/10.3390/ijms21249739)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Carbajal L, Biswas A, Niswander LM, Prizant H & & Hammes SR 2011 GPCR/EGFR cross talk is conserved in gonadal and adrenal steroidogenesis but is uniquely regulated by matrix metalloproteinases 2 and 9 in the ovary. Molecular Endocrinology 25 10551065. (https://doi.org/10.1210/me.2010-0410)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cha KY, Han SY, Chung HM, Choi DH, Lim JM, Lee WS, Ko JJ & & Yoon TK 2000 Pregnancies and deliveries after in vitro maturation culture followed by in vitro fertilization and embryo transfer without stimulation in women with polycystic ovary syndrome. Fertility and Sterility 73 978983. (https://doi.org/10.1016/s0015-0282(0000422-2)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chang SY, Chen YW, Chenier I, Sle MT & & Zhang SL 2011 Angiotensin II type II receptor deficiency accelerates the development of nephropathy in type I diabetes via oxidative stress and ACE2. Experimental Diabetes Research 2011 521076. (https://doi.org/10.1155/2011/521076)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chen X, Gong L, Li Q, Hu J, Liu X, Wang Y, Bai J, Ran X, Wu J, Ge Q, et al.2019 The appropriate remodeling of extracellular matrix is the key molecular signature in subcutaneous adipose tissue following Roux-en-Y gastric bypass. Life Sciences 218 265273. (https://doi.org/10.1016/j.lfs.2018.12.051)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chen C, Li S, Hu C, Cao W, Fu Q, Li J, Zheng L & & Huang J 2021 Protective effects of Puerarin on premature ovarian failure via regulation of Wnt/β-catenin signaling pathway and oxidative stress. Reproductive Sciences 28 982990. (https://doi.org/10.1007/s43032-020-00325-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cheng H, Zhong W, Wang L, Zhang Q, Ma X, Wang Y, Wang S, He C, Wei Q & & Fu C 2023 Effects of shear stress on vascular endothelial functions in atherosclerosis and potential therapeutic approaches. Biomedicine and Pharmacotherapy 158 114198. (https://doi.org/10.1016/j.biopha.2022.114198)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Emani S, Mayer JE Jr & & Emani SM 2011 Gene regulation of extracellular matrix remodeling in human bone marrow stem cell-seeded tissue-engineered grafts. Tissue Engineering. Part A 17 23792388. (https://doi.org/10.1089/ten.TEA.2010.0628)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Feng Y, Li M, Wang S, Cong W, Hu G, Song Y, Xiao H, Dong E & & Zhang Y 2020 Paired box 6 inhibits cardiac fibroblast differentiation. Biochemical and Biophysical Research Communications 528 561566. (https://doi.org/10.1016/j.bbrc.2020.05.146)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gilchrist RB, Ritter LJ & & Armstrong DT 2004 Oocyte-somatic cell interactions during follicle development in mammals. Animal Reproduction Science 82–83 431446. (https://doi.org/10.1016/j.anireprosci.2004.05.017)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gilmore AP, Owens TW, Foster FM & & Lindsay J 2009 How adhesion signals reach a mitochondrial conclusion--ECM regulation of apoptosis. Current Opinion in Cell Biology 21 654661. (https://doi.org/10.1016/j.ceb.2009.05.009)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Golubovskaya VM, Gross S, Kaur AS, Wilson RI, Xu LH, Yang XH & & Cance WG 2003 Simultaneous inhibition of focal adhesion kinase and SRC enhances detachment and apoptosis in colon cancer cell lines. Molecular Cancer Research 1 755764.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Han X, Xue R, Yuan HJ, Wang TY, Lin J, Zhang J, Liang B & & Tan JH 2017 MicroRNA-21 plays a pivotal role in the oocyte-secreted factor-induced suppression of cumulus cell apoptosis. Biology of Reproduction 96 11671180. (https://doi.org/10.1093/biolre/iox044)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Han X, Zhang M, Yuan HJ, Wang GL, Zhao XY, Li ZB, Gong S & & Tan JH 2022 Expression profiling and function analysis identified new microRNAs regulating cumulus expansion and apoptosis in cumulus cells. Molecular Human Reproduction 28. (https://doi.org/10.1093/molehr/gaab070)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hassani F, Oryan S, Eftekhari-Yazdi P, Bazrgar M, Moini A, Nasiri N & & Sharifi-Zarchi A 2019 Downregulation of extracellular matrix and cell adhesion molecules in cumulus cells of infertile polycystic ovary syndrome women with and without insulin resistance. Cell Journal 21 3542. (https://doi.org/10.22074/cellj.2019.5576)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • He Y, Liu Y, Gong J, Liu C, Zhang H & & Wu H 2019 Identification of key pathways and candidate genes in pancreatic ductal adenocarcinoma using bioinformatics analysis. Oncology Letters 17 37513764. (https://doi.org/10.3892/ol.2019.10041)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hoskin V, Szeto A, Ghaffari A, Greer PA, Côté GP & & Elliott BE 2015 Ezrin regulates focal adhesion and invadopodia dynamics by altering calpain activity to promote breast cancer cell invasion. Molecular Biology of the Cell 26 34643479. (https://doi.org/10.1091/mbc.E14-12-1584)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hwang S, Tatsi C, Kuehn HS, Niemela JE, Stoddard J, Su Y, Lodish M, Uzel G, Spolski R, Leonard WJ, et al.2022 Cushing syndrome and glucocorticoids: T-cell lymphopenia, apoptosis, and rescue by IL-21. Journal of Allergy and Clinical Immunology 149 302314. (https://doi.org/10.1016/j.jaci.2021.05.031)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Insua-Rodríguez J & & Oskarsson T 2016 The extracellular matrix in breast cancer. Advanced Drug Delivery Reviews 97 4155. (https://doi.org/10.1016/j.addr.2015.12.017)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jiao Y, Zhu S, Li J, Jam Zaheer A, Li M & & Huang B 2020 PS48 promotes in vitro maturation and developmental competence of porcine oocytes through activating PI3K/Akt signalling pathway. Reproduction in Domestic Animals 55 16781687. (https://doi.org/10.1111/rda.13818)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kaneko T, Saito H, Toya M, Satio T, Nakahara K & & Hiroi M 2000 Hyaluronic acid inhibits apoptosis in granulosa cells via CD44. Journal of Assisted Reproduction and Genetics 17 162167. (https://doi.org/10.1023/a:1009470206468)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kashima Y, Shibahara D, Suzuki A, Muto K, Kobayashi IS, Plotnick D, Udagawa H, Izumi H, Shibata Y, Tanaka K, et al.2021 Single-cell analyses reveal diverse mechanisms of resistance to EGFR tyrosine kinase inhibitors in lung cancer. Cancer Research 81 48354848. (https://doi.org/10.1158/0008-5472.CAN-20-2811)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kitasaka H, Kawai T, Hoque SAM, Umehara T, Fujita Y & & Shimada M 2018 Inductions of granulosa cell luteinization and cumulus expansion are dependent on the fibronectin-integrin pathway during ovulation process in mice. PLoS One 13 e0192458. (https://doi.org/10.1371/journal.pone.0192458)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Li X, Zhuang J & & Uhal BD 2018 Local activation of the pulmonary extravascular angiotensin system induces epithelial apoptosis and lung fibrosis. Journal of Lung, Pulmonary and Respiratory Research 5 192200. (https://doi.org/10.15406/jlprr.2018.05.00191)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Linder S 2007 The matrix corroded: podosomes and invadopodia in extracellular matrix degradation. Trends in Cell Biology 17 107117. (https://doi.org/10.1016/j.tcb.2007.01.002)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Liu J, Zhu W, Jiang CM, Feng Y, Xia YY, Zhang QY, Xu PF & & Zhang M 2018 Mammalian target of rapamycin Complex 1 activation disrupts the low-density lipoprotein receptor pathway: a novel mechanism for extracellular matrix accumulation in human peritoneal mesothelial cells. American Journal of Nephrology 48 357368. (https://doi.org/10.1159/000494144)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Liu H, Wei S, Zhang L, Yuan C, Duan Y & & Wang Q 2019 Secreted phosphoprotein 1 promotes the development of small cell lung cancer cells by inhibiting autophagy and apoptosis. Pathology Oncology Research 25 14871495. (https://doi.org/10.1007/s12253-018-0504-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Moulavi F & & Hosseini SM 2018 Diverse patterns of cumulus cell expansion during in vitro maturation reveal heterogeneous cellular and molecular features of oocyte competence in dromedary camel. Theriogenology 119 259267. (https://doi.org/10.1016/j.theriogenology.2018.07.010)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nagyova E 2018 The biological role of hyaluronan-rich oocyte-cumulus extracellular matrix in female reproduction. International Journal of Molecular Sciences 19. (https://doi.org/10.3390/ijms19010283)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nagyová E, Němcová L & & Camaioni A 2021 Cumulus extracellular matrix is an important part of oocyte microenvironment in ovarian follicles: its remodeling and proteolytic degradation. International Journal of Molecular Sciences 23. (https://doi.org/10.3390/ijms23010054)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pan LZ, Cheng H, Zhang J, Gong S, Tian XD, Pan CJ, Luo MJ & & Tan JH 2021 In vivo zearalenone exposure dose-dependently compromises mouse oocyte competence by impairing chromatin configuration and gene transcription. Reproduction, Fertility, and Development 33 229238. (https://doi.org/10.1071/RD20273)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Park HJ, Chae SK, Kim JW, Yang SG, Jung JM, Kim MJ, Wee G, Lee DS, Kim SU & & Koo DB 2017 Ganglioside GM3 induces cumulus cell apoptosis through inhibition of epidermal growth factor receptor-mediated PI3K/AKT signaling pathways during in vitro maturation of pig oocytes. Molecular Reproduction and Development 84 702711. (https://doi.org/10.1002/mrd.22848)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Racowsky C & & Needleman DJ 2018 Cumulus cell gene expression as a potential biomarker for oocyte quality. Fertility and Sterility 109 438439. (https://doi.org/10.1016/j.fertnstert.2017.12.013)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Raei Sadigh A, Darabi M, Salmassi A, Hamdi K, Farzadi L, Ghasemzadeh A, Fattahi A & & Nouri M 2020 Fractalkine and apoptotic/anti-apoptotic markers in granulosa cells of women with polycystic ovarian syndrome. Molecular Biology Reports 47 35933603. (https://doi.org/10.1007/s11033-020-05452-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Russell DL & & Salustri A 2006 Extracellular matrix of the cumulus-oocyte complex. Seminars in Reproductive Medicine 24 217227. (https://doi.org/10.1055/s-2006-948551)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Samereh S, Hajarian H, Karamishabankareh H, Soltani L & & Foroutanifar S 2021 Effects of different concentrations of Chir98014 as an activator of Wnt/beta-catenin signaling pathway on oocyte in-vitro maturation and subsequent embryonic development in Sanjabi ewes. Reproduction in Domestic Animals 56 965971. (https://doi.org/10.1111/rda.13938)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Shepel EA, Voznesenskaya TY, Blashkiv TV & & Yanchii RI 2016. Cumulus cell genes as potential biomarkers of oocyte and embryo developmental competence. Fiziolohichnyĭ Zhurnal 62 107113.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sidahmed AME, León AJ, Bosinger SE, Banner D, Danesh A, Cameron MJ & & Kelvin DJ 2012 CXCL10 contributes to p38-mediated apoptosis in primary T lymphocytes in vitro. Cytokine 59 433441. (https://doi.org/10.1016/j.cyto.2012.05.002)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Thoumine O, Nerem RM & & Girard PR 1995 Changes in organization and composition of the extracellular matrix underlying cultured endothelial cells exposed to laminar steady shear stress. Laboratory Investigation 73 565576.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Trounson A, Wood C & & Kausche A 1994 In vitro maturation and the fertilization and developmental competence of oocytes recovered from untreated polycystic ovarian patients. Fertility and Sterility 62 353362. (https://doi.org/10.1016/s0015-0282(1656891-5)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Uyar A, Torrealday S & & Seli E 2013 Cumulus and granulosa cell markers of oocyte and embryo quality. Fertility and Sterility 99 979997. (https://doi.org/10.1016/j.fertnstert.2013.01.129)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wala SJ, Karamchandani JR, Saleeb R, Evans A, Ding Q, Ibrahim R, Jewett M, Pasic M, Finelli A, Pace K, et al.2015 An integrated genomic analysis of papillary renal cell carcinoma type 1 uncovers the role of focal adhesion and extracellular matrix pathways. Molecular Oncology 9 16671677. (https://doi.org/10.1016/j.molonc.2015.04.007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wang SH, Huang Y, Yuan Y, Xia WQ, Wang P & & Huang R 2014 LDL receptor knock-out mice show impaired spatial cognition with hippocampal vulnerability to apoptosis and deficits in synapses. Lipids in Health and Disease 13 175. (https://doi.org/10.1186/1476-511X-13-175)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wang Y, Zhang T, Guo L, Ren T & & Yang Y 2019 Stromal extracellular matrix is a microenvironmental cue promoting resistance to EGFR tyrosine kinase inhibitors in lung cancer cells. International Journal of Biochemistry and Cell Biology 106 96106. (https://doi.org/10.1016/j.biocel.2018.11.001)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wu YH, Yang CY, Chien WL, Lin KI & & Lai MZ 2012 Removal of syndecan-1 promotes TRAIL-induced apoptosis in myeloma cells. Journal of Immunology 188 29142921. (https://doi.org/10.4049/jimmunol.1102065)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Xian X, Gopal S & & Couchman JR 2010 Syndecans as receptors and organizers of the extracellular matrix. Cell and Tissue Research 339 3146. (https://doi.org/10.1007/s00441-009-0829-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yokoo M & & Sato E 2004 Cumulus-oocyte complex interactions during oocyte maturation. International Review of Cytology 235 251291. (https://doi.org/10.1016/S0074-7696(0435006-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yu X, Liu Q, Wang Y, Bao Y, Jiang Y, Li M, Li Z, Wang B, Yu L, Wang S, et al.2022 Depleted long noncoding RNA GAS5 relieves intervertebral disc degeneration via microRNA-17-3p/Ang-2. Oxidative Medicine and Cellular Longevity 2022 1792412. (https://doi.org/10.1155/2022/1792412)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zhou M, Zhu Y, Zhou Z, Qi F, Zheng S, Gao S, Li Y, Liu Y & & Du J 2022 Fibroblast-secreted phosphoprotein 1 mediates extracellular matrix deposition and inhibits smooth muscle cell contractility in Marfan syndrome aortic aneurysm. Journal of Cardiovascular Translational Research 15 959970. (https://doi.org/10.1007/s12265-022-10239-8)

    • PubMed
    • Search Google Scholar
    • Export Citation