CITED4 mediates proliferation, apoptosis and steroidogenesis of Hu sheep granulosa cells in vitro

in Reproduction
View More View Less
  • 1 Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, China
  • 2 Hu Sheep Academy, Nanjing Agricultural University, Nanjing, China
  • 3 National Experimental Teaching Demonstration Centre of Animal Science, Nanjing Agricultural University, Nanjing, China

Correspondence should be addressed to F Wang; Email: caeet@njau.edu.cn
Restricted access

Being a novel target of luteinizing hormone (LH), the effect of CREB-binding protein/P300-interacting trans-activator with ED-rich tail member 4 (CITED4) gene on the proliferation, apoptosis, and steroidogenesis of ovarian granulosa cells (GCs) in Hu sheep was investigated. The presence of CITED4, CREB-binding protein (CBP), CCAAT/enhancer-binding protein alpha (C/EBPα) and -beta (C/EBPβ) proteins was demonstrated in GCs and luteal cells. CITED4 protein in GCs was induced by LH, and CITED4 overexpression moderately increased GC responses to LH. In contrast, CITED4 knockdown in GCs decreased prostaglandin (PGE2)-induced LH target gene levels. Moreover, PGE2-stimulated CITED4 mRNA expression was blocked by ERK1/2 inhibition (U0126), suggesting that CITED4 is a downstream target of the ERK1/2 pathway in sheep GCs. In contrast to CITED4 knockdown, CITED4 overexpression promoted GC proliferation, inhibited apoptosis, upregulated cell cycle-related genes, and downregulated apoptosis-related genes. Additionally, CITED4 overexpression induced cell cycle transition from S to G2/M phase. No effect was observed with CITED4 knockdown. CITED4 overexpression increased progesterone (P4) production levels and STAR mRNA expression, whereas CITED4 knockdown decreased P4 production and STAR and 3β-HSD mRNA expression levels. Thus, our results suggest that CITED4 is involved in regulating the expression of LH-induced genes and the ERK1/2 pathway and the proliferation, apoptosis, and steroidogenesis in Hu sheep GCs by modulating the expression of related genes. These findings will help understand the role of CITED4 in follicular development and ovulation of pre-ovulatory follicles.

 

     An official journal of

    Society for Reproduction and Fertility

 

Sept 2018 onwards Past Year Past 30 Days
Abstract Views 350 350 156
Full Text Views 23 23 8
PDF Downloads 21 21 11
  • Aylon Y & Kupiec M 2005 Cell cycle-dependent regulation of double-strand break repair: a role for the CDK. Cell Cycle 4 259261. (https://doi.org/10.4161/cc.4.2.1429)

    • Search Google Scholar
    • Export Citation
  • Ben-Ami I, Freimann S, Armon L, Dantes A, Strassburger D, Friedler S, Raziel A, Seger R, Ron-El R & Amsterdam A 2006 PGE2 up-regulates EGF-like growth factor biosynthesis in human granulosa cells: new insights into the coordination between PGE2 and LH in ovulation. Molecular Human Reproduction 12 593599. (https://doi.org/10.1093/molehr/gal068)

    • Search Google Scholar
    • Export Citation
  • Buck SH, Chiu D & Saito RM 2009 The cyclin-dependent kinase inhibitors, cki-1 and cki-2, act in overlapping but distinct pathways to control cell cycle quiescence during C. elegans development. Cell Cycle 8 26132620. (https://doi.org/10.4161/cc.8.16.9354)

    • Search Google Scholar
    • Export Citation
  • Carletti MZ & Christenson LK 2009 Rapid effects of LH on gene expression in the mural granulosa cells of mouse periovulatory follicles. Reproduction 137 843855. (https://doi.org/10.1530/REP-08-0457)

    • Search Google Scholar
    • Export Citation
  • Casarini L, Riccetti L, De Pascali F, Gilioli L, Marino M, Vecchi E, Morini D, Nicoli A, La Sala GB & Simoni M 2017 Estrogen modulates specific life and death signals induced by LH and hCG in human primary granulosa cells in vitro. International Journal of Molecular Sciences 18 926. (https://doi.org/10.3390/ijms18050926)

    • Search Google Scholar
    • Export Citation
  • De Cesaro MP, Dos Santos JT, Ferst JG, Nobrega Jr JE, Rosa P, Rovani MT, Ilha GF, Bohrer RC, Ferreira R & Gasperin BG et al. 2018 Natriuretic peptide system regulation in granulosa cells during follicle deviation and ovulation in cattle. Reproduction in Domestic Animals 53 710717. (https://doi.org/10.1111/rda.13161)

    • Search Google Scholar
    • Export Citation
  • Dong Y, Sui L, Sugimoto K, Tai Y & Tokuda M 2001 Cyclin D1-CDK4 complex, a possible critical factor for cell proliferation and prognosis in laryngeal squamous cell carcinomas. International Journal of Cancer 95 209215. (https://doi.org/10.1002/1097-0215(20010720)95:4<209::aid-ijc1036>3.0.co;2-r)

    • Search Google Scholar
    • Export Citation
  • Espey LL & Richards JS 2002 Temporal and spatial patterns of ovarian gene transcription following an ovulatory dose of gonadotropin in the rat. Biology of Reproduction 67 16621670. (https://doi.org/10.1095/biolreprod.102.005173)

    • Search Google Scholar
    • Export Citation
  • Fan HY, Liu Z, Shimada M, Sterneck E, Johnson PF, Hedrick SM & Richards JS 2009 MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for female fertility. Science 324 938941. (https://doi.org/10.1126/science.1171396)

    • Search Google Scholar
    • Export Citation
  • Fan HY, Liu Z, Johnson PF & Richards JS 2011 CCAAT/enhancer-binding proteins (C/EBP)-alpha and -beta are essential for ovulation, luteinization, and the expression of key target genes. Molecular Endocrinology 25 253268. (https://doi.org/10.1210/me.2010-0318)

    • Search Google Scholar
    • Export Citation
  • Filicori M, Cognigni GE, Samara A, Melappioni S, Perri T, Cantelli B, Parmegiani L, Pelusi G & Dealoysio D 2002 The use of LH activity to drive folliculogenesis: exploring uncharted territories in ovulation induction. Human Reproduction Update 8 543557. (https://doi.org/10.1093/humupd/8.6.543)

    • Search Google Scholar
    • Export Citation
  • Gupta C, Chapekar T, Chhabra Y, Singh P, Sinha S & Luthra K 2012 Differential response to sustained stimulation by hCG and LH on goat ovarian granulosa cells. Indian Journal of Medical Research 135 331340. (https://doi.org/10.4103/0971-5916.93429)

    • Search Google Scholar
    • Export Citation
  • Hackbart KS, Bender RW, Carvalho PD, Vieira LM, Dresch AR, Guenther JN, Gencoglu H, Nascimento AB, Shaver RD & Wiltbank MC 2017 Effects of propylene glycol or elevated luteinizing hormone during follicle development on ovulation, fertilization, and early embryo development. Biology of Reproduction 97 550563. (https://doi.org/10.1093/biolre/iox050)

    • Search Google Scholar
    • Export Citation
  • Jiang JT, Ma YN, Gao XY, Jin YF, Ma XC, Yan WJ, Zhang H, Wang W, Tian T & Zhao QQ et al. 2016 Downregulation of Cited1 suppresses cell proliferation by inducing G2/M arrest of the cell cycle in non-small-cell lung cancer cell lines. International Journal of Clinical and Experimental Pathology 9 1158311590.

    • Search Google Scholar
    • Export Citation
  • Kiraz Y, Adan A, Kartal Yandim M & Baran Y 2016 Major apoptotic mechanisms and genes involved in apoptosis. Tumour Biology 37 84718486. (https://doi.org/10.1007/s13277-016-5035-9)

    • Search Google Scholar
    • Export Citation
  • Korsmeyer SJ, Shutter JR, Veis DJ, Merry DE & Oltvai ZN 1993 Bcl-2/Bax – a rheostat that regulates an antioxidant pathway and cell-death. Seminars in Cancer Biology 4 327332. (https://doi.org/10.1016/0167-8140(9390160-A)

    • Search Google Scholar
    • Export Citation
  • Lavi O, Ginsberg D & Louzoun Y 2011 Regulation of modular cyclin and CDK feedback loops by an E2F transcription oscillator in the mammalian cell cycle. Mathematical Biosciences and Engineering 8 445461. (https://doi.org/10.3934/mbe.2011.8.445)

    • Search Google Scholar
    • Export Citation
  • Lee S, Shuman JD, Guszczynski T, Sakchaisri K, Sebastian T, Copeland TD, Miller M, Cohen MS, Taunton J & Smart RC et al. 2010 RSK-mediated phosphorylation in the C/EBP{beta} leucine zipper regulates DNA binding, dimerization, and growth arrest activity. Molecular and Cellular Biology 30 26212635. (https://doi.org/10.1128/MCB.00782-09)

    • Search Google Scholar
    • Export Citation
  • Matsuda F, Inoue N, Manabe N & Ohkura S 2012 Follicular growth and atresia in mammalian ovaries: regulation by survival and death of granulosa cells. Journal of Reproduction and Development 58 4450. (https://doi.org/10.1262/jrd.2011-012)

    • Search Google Scholar
    • Export Citation
  • McGee EA & Hsueh AJ 2000 Initial and cyclic recruitment of ovarian follicles. Endocrine Reviews 21 200214. (https://doi.org/10.1210/edrv.21.2.0394)

    • Search Google Scholar
    • Export Citation
  • Miake J, Notsu T, Higaki K, Hidaka K, Morisaki T, Yamamoto K & Hisatome I 2017 Cited4 is related to cardiogenic induction and maintenance of proliferation capacity of embryonic stem cell-derived cardiomyocytes during in vitro cardiogenesis. PLoS ONE 12 e0183225. (https://doi.org/10.1371/journal.pone.0183225)

    • Search Google Scholar
    • Export Citation
  • Mizutani T, Ju Y, Imamichi Y, Osaki T, Yazawa T, Kawabe S, Ishikane S, Matsumura T, Kanno M & Kamiki Y et al. 2014 C/EBPβ (CCAAT/enhancer-binding protein β) mediates progesterone production through transcriptional regulation in co-operation with SF-1 (steroidogenic factor-1). Biochemical Journal 460 459471. (https://doi.org/10.1042/BJ20131522)

    • Search Google Scholar
    • Export Citation
  • Mizutani T, Ishikane S, Kawabe S, Umezawa A & Miyamoto K 2015 Transcriptional regulation of genes related to progesterone production. Endocrine Journal 62 757763. (https://doi.org/10.1507/endocrj.EJ15-0260)

    • Search Google Scholar
    • Export Citation
  • Newman DM, Jones PL & Ingram BA 2008 Age-related changes in ovarian characteristics, plasma sex steroids and fertility during pubertal development in captive female Murray cod Maccullochella peelii peelii. Comparative Biochemistry and Physiology: Part A, Molecular and Integrative Physiology 150 444451. (https://doi.org/10.1016/j.cbpa.2008.05.005)

    • Search Google Scholar
    • Export Citation
  • Niringiyumukiza JD, Cai H & Xiang W 2018 Prostaglandin E2 involvement in mammalian female fertility: ovulation, fertilization, embryo development and early implantation. Reproductive Biology and Endocrinology 16 43. (https://doi.org/10.1186/s12958-018-0359-5)

    • Search Google Scholar
    • Export Citation
  • Padmanabhan V, Salvetti NR, Matiller V & Ortega HH 2014 Developmental programming: prenatal steroid excess disrupts key members of intraovarian steroidogenic pathway in sheep. Endocrinology 155 36493660.(https://doi.org/10.1210/en.2014-1266)

    • Search Google Scholar
    • Export Citation
  • Palermo R 2007 Differential actions of FSH and LH during folliculogenesis. Reproductive Biomedicine Online 15 326337. (https://doi.org/10.1016/S1472-6483(1060347-1)

    • Search Google Scholar
    • Export Citation
  • Park JY, Su YQ, Ariga M, Law E, Jin SL & Conti M 2004 EGF-like growth factors as mediators of LH action in the ovulatory follicle. Science 303 682684.(https://doi.org/10.1126/science.1092463)

    • Search Google Scholar
    • Export Citation
  • Rogers MA, Kalter V, Marcias G, Zapatka M, Barbus S & Lichter P 2016 CITED4 gene silencing in colorectal cancer cells modulates adherens/tight junction gene expression and reduces cell proliferation. Journal of Cancer Research and Clinical Oncology 142 225237. (https://doi.org/10.1007/s00432-015-2011-5)

    • Search Google Scholar
    • Export Citation
  • Sanchez AM, Somigliana E, Vercellini P, Pagliardini L, Candiani M & Vigano P 2016 Endometriosis as a detrimental condition for granulosa cell steroidogenesis and development: from molecular alterations to clinical impact. Journal of Steroid Biochemistry and Molecular Biology 155 3546. (https://doi.org/10.1016/j.jsbmb.2015.07.023)

    • Search Google Scholar
    • Export Citation
  • Shimada M & Yamashita Y 2011 The key signaling cascades in granulosa cells during follicular development and ovulation process. Journal of Mammalian Ova Research 28 2531. (https://doi.org/10.1274/jmor.28.25)

    • Search Google Scholar
    • Export Citation
  • Skory RM, Xu Y, Shea LD & Woodruff TK 2015 Engineering the ovarian cycle using in vitro follicle culture. Human Reproduction 30 13861395. (https://doi.org/10.1093/humrep/dev052)

    • Search Google Scholar
    • Export Citation
  • Spampanato C, De Maria S, Sarnataro M, Giordano E, Zanfardino M, Baiano S, Carteni M & Morelli F 2012 Simvastatin inhibits cancer cell growth by inducing apoptosis correlated to activation of Bax and down-regulation of BCL-2 gene expression. International Journal of Oncology 40 935941. (https://doi.org/10.3892/ijo.2011.1273)

    • Search Google Scholar
    • Export Citation
  • Sun J, Du Y, Song Q, Nan J, Guan P, Guo J, Wang X, Yang J & Zhao C 2019 E2F is required for STAT3-mediated upregulation of cyclin B1 and Cdc2 expressions and contributes to G2-M phase transition. Acta Biochimica and Biophysica Sinica 51 313322. (https://doi.org/10.1093/abbs/gmy174)

    • Search Google Scholar
    • Export Citation
  • Tang H, Liu Y, Li J, Li G, Chen Y, Yin Y, Guo Y, Cheng CH, Liu X & Lin H 2017 LH signaling induced ptgs2a expression is required for ovulation in zebrafish. Molecular and Cellular Endocrinology 447 125133. (https://doi.org/10.1016/j.mce.2017.02.042)

    • Search Google Scholar
    • Export Citation
  • Tosca L, Rame C, Chabrolle C, Tesseraud S & Dupont J 2010 Metformin decreases IGF1-induced cell proliferation and protein synthesis through AMP-activated protein kinase in cultured bovine granulosa cells. Reproduction 139 409418. (https://doi.org/10.1530/REP-09-0351)

    • Search Google Scholar
    • Export Citation
  • Yahata T, Takedatsu H, Dunwoodie SL, Bragança J, Swingler T, Withington SL, Hur J, Coser KR, Isselbacher KJ & Bhattacharya S et al. 2002 Cloning of mouse Cited4, a member of the CITED family p300/CBP-binding transcriptional coactivators: induced expression in mammary epithelial cells. Genomics 80 601613. (https://doi.org/10.1006/geno.2002.7005)

    • Search Google Scholar
    • Export Citation
  • Yamashita Y, Kawashima I, Yanai Y, Nishibori M, Richards JS & Shimada M 2007 Hormone-induced expression of tumor necrosis factor alpha-converting enzyme/A disintegrin and metalloprotease-17 impacts porcine cumulus cell oocyte complex expansion and meiotic maturation via ligand activation of the epidermal growth factor receptor. Endocrinology 148 61646175. (https://doi.org/10.1210/en.2007-0195)

    • Search Google Scholar
    • Export Citation
  • Yao X, Yang H, Zhang Y, Ren C, Nie H, Fan Y, Zhou W, Wang S, Feng X & Wang F 2017a Characterization of GALNTL5 gene sequence and expression in ovine testes and sperm. Theriogenology 95 5461. (https://doi.org/10.1016/j.theriogenology.2017.02.018)

    • Search Google Scholar
    • Export Citation
  • Yao X, Zhang G, Guo Y, Ei-Samahy M, Wang S, Wan Y, Han L, Liu Z, Wang F & Zhang Y 2017b Vitamin D receptor expression and potential role of vitamin D on cell proliferation and steroidogenesis in goat ovarian granulosa cells. Theriogenology 102 162173. (https://doi.org/10.1016/j.theriogenology.2017.08.002)

    • Search Google Scholar
    • Export Citation
  • Yao X, Wang Z, El-Samahy MA, Ren C, Liu Z, Wang F & You P 2020 Roles of vitamin D and its receptor in the proliferation and apoptosis of luteinised granulosa cells in the goat. Reproduction, Fertility, and Development 32 335348. (https://doi.org/10.1071/RD18442)

    • Search Google Scholar
    • Export Citation
  • Yuan X, Zhou X, He Y, Zhong Y, Zhang A, Zhang Z, Zhang H & Li J 2018 C/EBPβ promotes STAT3 expression and affects cell apoptosis and proliferation in porcine ovarian granulosa cells. Genes 9 295. (https://doi.org/10.3390/genes9060295)

    • Search Google Scholar
    • Export Citation
  • Zhang YL, Xia Y, Yu C, Richards JS, Liu J & Fan HY 2014 CBP-CITED4 is required for luteinizing hormone-triggered target gene expression during ovulation. Molecular Human Reproduction 20 850860. (https://doi.org/10.1093/molehr/gau040)

    • Search Google Scholar
    • Export Citation
  • Zhang GM, Deng MT, Zhang YL, Fan YX, Wan YJ, Nie HT, Wang ZY, Wang F & Lei ZH 2016 Effect of PGC-1alpha overexpression or silencing on mitochondrial apoptosis of goat luteinized granulosa cells. Journal of Bioenergetics and Biomembranes 48 493507. (https://doi.org/10.1007/s10863-016-9684-6)

    • Search Google Scholar
    • Export Citation
  • Zhang GM, Deng MT, Lei ZH, Wan YJ, Nie HT, Wang ZY, Fan YX, Wang F & Zhang YL 2017 Effects of NRF1 on steroidogenesis and apoptosis in goat luteinized granulosa cells. Reproduction 154 111122. (https://doi.org/10.1530/REP-16-0583)

    • Search Google Scholar
    • Export Citation
  • Zhen YH, Wang L, Riaz H, Wu JB, Yuan YF, Han L, Wang YL, Zhao Y, Dan Y & Huo LJ 2014 Knockdown of CEBPbeta by RNAi in porcine granulosa cells resulted in S phase cell cycle arrest and decreased progesterone and estradiol synthesis. Journal of Steroid Biochemistry and Molecular Biology 143 9098. (https://doi.org/10.1016/j.jsbmb.2014.02.013)

    • Search Google Scholar
    • Export Citation