Telomere length and telomerase activity during folliculogenesis in mammals

Esra Gozde Kosebent, Fatma Uysal, Saffet Ozturk, Esra Gozde Kosebent, Fatma Uysal, Saffet Ozturk

Abstract

Telomeres are repetitive non-coding DNA sequences located at the ends of chromosomes in eukaryotic cells. Their most important function is to protect chromosome ends from being recognized as DNA damage. They are also implicated in meiosis and synapse formation. The length of telomeres inevitably shortens at the end of each round of DNA replication and, also, as a consequence of the exposure to oxidative stress and/or genotoxic agents. The enzyme telomerase contributes to telomere lengthening. It has been reported that telomerase is exclusively expressed in germ cells, granulosa cells, early embryos, stem cells, and various types of cancerous cells. Granulosa cells undergo many mitotic divisions and either granulosa cells or oocytes are exposed to a variety of genotoxic agents throughout folliculogenesis; thus, telomerase plays an important role in the maintenance of telomere length. In this review article, we have comprehensively evaluated the studies focusing on the regulation of telomerase expression and activity, as well as telomere length, during folliculogenesis from primordial to antral follicles, in several mammalian species including mice, bovines, and humans. Also, the possible relationships between female infertility caused by follicular development defects and alterations in the telomeres and/or telomerase activity are discussed.

Keywords: Female infertility; Granulosa cell; Oocyte; Telomerase; Telomere.

Figures

Fig. 1.
Fig. 1.
Schematic diagram showing telomere structure, telomere-associated proteins (TRF1, TRF2, POT1, TIN2, TPP1, and RAP1; forming the shelterin complex), and telomerase in a mammalian oocyte. The 3' overhang of telomere end enters the doubled-stranded DNA to create a displacement (D-loop) and a telomere (T-loop) loop. The shortened telomeres are elongated by the telomerase enzyme, composed of a TERT and a TERC subunits, as well as by other components.
Fig. 2.
Fig. 2.
Telomerase activity and telomere length during folliculogenesis. The studies performed in pigs and bovines suggest that the telomerase activity gradually decreases and the length of telomeres progressively increases from primordial follicles to antral follicles. The blue line represents telomerase activity, whereas the red line represents telomere length.

References

    1. de Lange T, Shiue L, Myers RM, Cox DR, Naylor SL, Killery AM, Varmus HE. Structure and variability of human chromosome ends. Mol Cell Biol 1990; 10: 518–527.
    1. Muller HJ. The remaking of chromosomes. Collect Net1938: 181-95.
    1. Klobutcher LA, Swanton MT, Donini P, Prescott DM. All gene-sized DNA molecules in four species of hypotrichs have the same terminal sequence and an unusual 3′ terminus. Proc Natl Acad Sci USA 1981; 78: 3015–3019.
    1. Blackburn EH, Gall JG. A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena. J Mol Biol 1978; 120: 33–53.
    1. Brown WR. Molecular cloning of human telomeres in yeast. Nature 1989; 338: 774–776.
    1. Calado RT, Dumitriu B. Telomere dynamics in mice and humans. Semin Hematol 2013; 50: 165–174.
    1. Iqbal K, Kues WA, Baulain U, Garrels W, Herrmann D, Niemann H. Species-specific telomere length differences between blastocyst cell compartments and ectopic telomere extension in early bovine embryos by human telomerase reverse transcriptase. Biol Reprod 2011; 84: 723–733.
    1. Gomes NM, Shay JW, Wright WE. Telomere biology in Metazoa. FEBS Lett 2010; 584: 3741–3751.
    1. Lingner J, Cech TR. Telomerase and chromosome end maintenance. Curr Opin Genet Dev 1998; 8: 226–232.
    1. Riethman H, Ambrosini A, Paul S. Human subtelomere structure and variation. Chromosome Res 2005; 13: 505–515.
    1. Azzalin CM, Nergadze SG, Giulotto E. Human intrachromosomal telomeric-like repeats: sequence organization and mechanisms of origin. Chromosoma 2001; 110: 75–82.
    1. Ruiz-Herrera A, García F, Azzalin C, Giulotto E, Egozcue J, Ponsà M, Garcia M. Distribution of intrachromosomal telomeric sequences (ITS) on Macaca fascicularis (Primates) chromosomes and their implication for chromosome evolution. Hum Genet 2002; 110: 578–586.
    1. Wellinger RJ, Sen D. The DNA structures at the ends of eukaryotic chromosomes. Eur J Cancer 1997; 33: 735–749.
    1. Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H, de Lange T. Mammalian telomeres end in a large duplex loop. Cell 1999; 97: 503–514.
    1. Azzalin CM, Reichenbach P, Khoriauli L, Giulotto E, Lingner J. Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends. Science 2007; 318: 798–801.
    1. Reig-Viader R, Vila-Cejudo M, Vitelli V, Buscà R, Sabaté M, Giulotto E, Caldés MG, Ruiz-Herrera A. Telomeric repeat-containing RNA (TERRA) and telomerase are components of telomeres during mammalian gametogenesis. Biol Reprod 2014; 90: 103.
    1. Reig-Viader R, Brieño-Enríquez MA, Khoriauli L, Toran N, Cabero L, Giulotto E, Garcia-Caldés M, Ruiz-Herrera A. Telomeric repeat-containing RNA and telomerase in human fetal oocytes. Hum Reprod 2013; 28: 414–422.
    1. Schoeftner S, Blasco MA. Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II. Nat Cell Biol 2008; 10: 228–236.
    1. Nergadze SG, Farnung BO, Wischnewski H, Khoriauli L, Vitelli V, Chawla R, Giulotto E, Azzalin CM. CpG-island promoters drive transcription of human telomeres. RNA 2009; 15: 2186–2194.
    1. Cusanelli E, Romero CA, Chartrand P. Telomeric noncoding RNA TERRA is induced by telomere shortening to nucleate telomerase molecules at short telomeres. Mol Cell 2013; 51: 780–791.
    1. Reig-Viader R, Garcia-Caldés M, Ruiz-Herrera A. Telomere homeostasis in mammalian germ cells: a review. Chromosoma 2016; 125: 337–351.
    1. Reig-Viader R, Capilla L, Vila-Cejudo M, Garcia F, Anguita B, Garcia-Caldés M, Ruiz-Herrera A. Telomere homeostasis is compromised in spermatocytes from patients with idiopathic infertility. Fertil Steril 2014; 102: 728–738.e1.
    1. De Boeck G, Forsyth RG, Praet M, Hogendoorn PC. Telomere-associated proteins: cross-talk between telomere maintenance and telomere-lengthening mechanisms. J Pathol 2009; 217: 327–344.
    1. de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 2005; 19: 2100–2110.
    1. Patel TN, Vasan R, Gupta D, Patel J, Trivedi M. Shelterin proteins and cancer. Asian Pac J Cancer Prev 2015; 16: 3085–3090.
    1. van Steensel B, de Lange T. Control of telomere length by the human telomeric protein TRF1. Nature 1997; 385: 740–743.
    1. Meng L, Hsu JK, Zhu Q, Lin T, Tsai RY. Nucleostemin inhibits TRF1 dimerization and shortens its dynamic association with the telomere. J Cell Sci 2011; 124: 3706–3714.
    1. Xin H, Liu D, Songyang Z. The telosome/shelterin complex and its functions. Genome Biol 2008; 9: 232.
    1. Sfeir A, Kosiyatrakul ST, Hockemeyer D, MacRae SL, Karlseder J, Schildkraut CL, de Lange T. Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication. Cell 2009; 138: 90–103.
    1. Palm W, de Lange T. How shelterin protects mammalian telomeres. Annu Rev Genet 2008; 42: 301–334.
    1. Yang D, Xiong Y, Kim H, He Q, Li Y, Chen R, Songyang Z. Human telomeric proteins occupy selective interstitial sites. Cell Res 2011; 21: 1013–1027.
    1. Wu P, van Overbeek M, Rooney S, de Lange T. Apollo contributes to G overhang maintenance and protects leading-end telomeres. Mol Cell 2010; 39: 606–617.
    1. Denchi EL, de Lange T. Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1. Nature 2007; 448: 1068–1071.
    1. Baumann P, Price C. Pot1 and telomere maintenance. FEBS Lett 2010; 584: 3779–3784.
    1. Wang F, Podell ER, Zaug AJ, Yang Y, Baciu P, Cech TR, Lei M. The POT1-TPP1 telomere complex is a telomerase processivity factor. Nature 2007; 445: 506–510.
    1. Chang S. Cancer chromosomes going to POT1. Nat Genet 2013; 45: 473–475.
    1. Yang Q, Zheng YL, Harris CC. POT1 and TRF2 cooperate to maintain telomeric integrity. Mol Cell Biol 2005; 25: 1070–1080.
    1. Diotti R, Loayza D. Shelterin complex and associated factors at human telomeres. Nucleus 2011; 2: 119–135.
    1. Cohen SB, Graham ME, Lovrecz GO, Bache N, Robinson PJ, Reddel RR. Protein composition of catalytically active human telomerase from immortal cells. Science 2007; 315: 1850–1853.
    1. Mitchell JR, Wood E, Collins K. A telomerase component is defective in the human disease dyskeratosis congenita. Nature 1999; 402: 551–555.
    1. Fu D, Collins K. Purification of human telomerase complexes identifies factors involved in telomerase biogenesis and telomere length regulation. Mol Cell 2007; 28: 773–785.
    1. Gardano L, Holland L, Oulton R, Le Bihan T, Harrington L. Native gel electrophoresis of human telomerase distinguishes active complexes with or without dyskerin. Nucleic Acids Res 2012; 40: e36.
    1. Autexier C, Lue NF. The structure and function of telomerase reverse transcriptase. Annu Rev Biochem 2006; 75: 493–517.
    1. Rouda S, Skordalakes E. Structure of the RNA-binding domain of telomerase: implications for RNA recognition and binding. Structure 2007; 15: 1403–1412.
    1. Lingner J, Hughes TR, Shevchenko A, Mann M, Lundblad V, Cech TR. Reverse transcriptase motifs in the catalytic subunit of telomerase. Science 1997; 276: 561–567.
    1. Nakamura TM, Morin GB, Chapman KB, Weinrich SL, Andrews WH, Lingner J, Harley CB, Cech TR. Telomerase catalytic subunit homologs from fission yeast and human. Science 1997; 277: 955–959.
    1. Drosopoulos WC, Prasad VR. The active site residue Valine 867 in human telomerase reverse transcriptase influences nucleotide incorporation and fidelity. Nucleic Acids Res 2007; 35: 1155–1168.
    1. Chen JL, Blasco MA, Greider CW. Secondary structure of vertebrate telomerase RNA. Cell 2000; 100: 503–514.
    1. Theimer CA, Feigon J. Structure and function of telomerase RNA. Curr Opin Struct Biol 2006; 16: 307–318.
    1. Theimer CA, Jády BE, Chim N, Richard P, Breece KE, Kiss T, Feigon J. Structural and functional characterization of human telomerase RNA processing and cajal body localization signals. Mol Cell 2007; 27: 869–881.
    1. Bryan TM, Englezou A, Gupta J, Bacchetti S, Reddel RR. Telomere elongation in immortal human cells without detectable telomerase activity. EMBO J 1995; 14: 4240–4248.
    1. Dunham MA, Neumann AA, Fasching CL, Reddel RR. Telomere maintenance by recombination in human cells. Nat Genet 2000; 26: 447–450.
    1. Cohen H, Sinclair DA. Recombination-mediated lengthening of terminal telomeric repeats requires the Sgs1 DNA helicase. Proc Natl Acad Sci USA 2001; 98: 3174–3179.
    1. Motta PM, Makabe S, Nottola SA. The ultrastructure of human reproduction. I. The natural history of the female germ cell: origin, migration and differentiation inside the developing ovary. Hum Reprod Update 1997; 3: 281–295.
    1. McLaren A, Monk M. X-chromosome activity in the germ cells of sex-reversed mouse embryos. J Reprod Fertil 1981; 63: 533–537.
    1. Borum K. Oogenesis in the mouse. A study of the meiotic prophase. Exp Cell Res 1961; 24: 495–507.
    1. Sánchez F, Smitz J. Molecular control of oogenesis. Biochim Biophys Acta 2012; 1822: 1896–1912.
    1. Sato E. Intraovarian control of selective follicular growth and induction of oocyte maturation in mammals. Proc Jpn Acad B 2015; 91: 76–91.
    1. Russo V, Berardinelli P, Capacchietti G, Scapolo PA. Localization of the telomerase catalytic subunit (TERT) in pig ovarian follicles. Vet Res Commun 2003; 27(Suppl 1): 623–626.
    1. Liu W, Zhu GJ. Expression of telomerase in human ovarian luteinized granulosa cells and its relationship to ovarian function. Zhonghua Fu Chan Ke Za Zhi 2003; 38: 402–404 (in Chinese).
    1. Ulaner GA, Hu JF, Vu TH, Giudice LC, Hoffman AR. Telomerase activity in human development is regulated by human telomerase reverse transcriptase (hTERT) transcription and by alternate splicing of hTERT transcripts. Cancer Res 1998; 58: 4168–4172.
    1. Schaetzlein S, Lucas-Hahn A, Lemme E, Kues WA, Dorsch M, Manns MP, Niemann H, Rudolph KL. Telomere length is reset during early mammalian embryogenesis. Proc Natl Acad Sci USA 2004; 101: 8034–8038.
    1. Eisenhauer KM, Gerstein RM, Chiu CP, Conti M, Hsueh AJ. Telomerase activity in female and male rat germ cells undergoing meiosis and in early embryos. Biol Reprod 1997; 56: 1120–1125.
    1. Bayne S, Li H, Jones ME, Pinto AR, van Sinderen M, Drummond A, Simpson ER, Liu JP. Estrogen deficiency reversibly induces telomere shortening in mouse granulosa cells and ovarian aging in vivo. Protein Cell 2011; 2: 333–346.
    1. Endo M, Kimura K, Kuwayama T, Monji Y, Iwata H. Effect of estradiol during culture of bovine oocyte-granulosa cell complexes on the mitochondrial DNA copies of oocytes and telomere length of granulosa cells. Zygote 2014; 22: 431–439.
    1. Liu L, Bailey SM, Okuka M, Muñoz P, Li C, Zhou L, Wu C, Czerwiec E, Sandler L, Seyfang A, Blasco MA, Keefe DL. Telomere lengthening early in development. Nat Cell Biol 2007; 9: 1436–1441.
    1. Lavranos TC, Mathis JM, Latham SE, Kalionis B, Shay JW, Rodgers RJ. Evidence for ovarian granulosa stem cells: telomerase activity and localization of the telomerase ribonucleic acid component in bovine ovarian follicles. Biol Reprod 1999; 61: 358–366.
    1. Russo V, Berardinelli P, Martelli A, Di Giacinto O, Nardinocchi D, Fantasia D, Barboni B. Expression of telomerase reverse transcriptase subunit (TERT) and telomere sizing in pig ovarian follicles. J Histochem Cytochem 2006; 54: 443–455.
    1. Betts DH, King WA. Telomerase activity and telomere detection during early bovine development. Dev Genet 1999; 25: 397–403.
    1. Gilchrist GC, Kurjanowicz P, Mereilles FV, King WA, LaMarre J. Telomere length and telomerase activity in bovine pre-implantation embryos in vitro. Reprod Domest Anim 2015; 50: 58–67.
    1. Meerdo LN, Reed WA, White KL. Telomere-to-centromere ratio of bovine clones, embryos, gametes, fetal cells, and adult cells. Cloning Stem Cells 2005; 7: 62–73.
    1. Wright DL, Jones EL, Mayer JF, Oehninger S, Gibbons WE, Lanzendorf SE. Characterization of telomerase activity in the human oocyte and preimplantation embryo. Mol Hum Reprod 2001; 7: 947–955.
    1. Turner S, Wong HP, Rai J, Hartshorne GM. Telomere lengths in human oocytes, cleavage stage embryos and blastocysts. Mol Hum Reprod 2010; 16: 685–694.
    1. Turner S, Hartshorne GM. Telomere lengths in human pronuclei, oocytes and spermatozoa. Mol Hum Reprod 2013; 19: 510–518.
    1. Wright WE, Piatyszek MA, Rainey WE, Byrd W, Shay JW. Telomerase activity in human germline and embryonic tissues and cells. Dev Genet 1996; 18: 173–179.
    1. Liu L, Franco S, Spyropoulos B, Moens PB, Blasco MA, Keefe DL. Irregular telomeres impair meiotic synapsis and recombination in mice. Proc Natl Acad Sci USA 2004; 101: 6496–6501.
    1. Liu L, Blasco M, Trimarchi J, Keefe D. An essential role for functional telomeres in mouse germ cells during fertilization and early development. Dev Biol 2002; 249: 74–84.
    1. Keefe DL, Franco S, Liu L, Trimarchi J, Cao B, Weitzen S, Agarwal S, Blasco MA. Telomere length predicts embryo fragmentation after in vitro fertilization in women— toward a telomere theory of reproductive aging in women. Am J Obstet Gynecol 2005; 192: 1256–1260, discussion :1260–1261.
    1. Keefe DL. Telomeres and meiosis in health and disease. Cell Mol Life Sci 2007; 64: 115–116.
    1. Keefe DL, Franco S, Liu L, et al. Short telomeres in eggs are associated with decreased outcomes following IVF – toward a telomere theory of reproductive aging in women. Am Soc Reprod Med Gen Prize Paper Session 10.2003.
    1. Wang W, Chen H, Li R, Ouyang N, Chen J, Huang L, Mai M, Zhang N, Zhang Q, Yang D. Telomerase activity is more significant for predicting the outcome of IVF treatment than telomere length in granulosa cells. Reproduction 2014; 147: 649–657.
    1. Chen H, Wang W, Mo Y, Ma Y, Ouyang N, Li R, Mai M, He Y, Bodombossou-Djobo MM, Yang D. Women with high telomerase activity in luteinised granulosa cells have a higher pregnancy rate during in vitro fertilisation treatment. J Assist Reprod Genet 2011; 28: 797–807.
    1. Liu JP, Li H. Telomerase in the ovary. Reproduction 2010; 140: 215–222.
    1. Si X, Shao C, Li J, Jia S, Tang W, Zhang J, Yang J, Wu X, Luo Y. Loss of p21 promoted tumorigenesis in the background of telomere dysfunctions induced by TRF2 and Wrn deficiency. Int J Biol Sci 2018; 14: 165–177.
    1. Garofola C, Gross GP. Dyskeratosis Congenita. StatPearls. Treasure Island (FL); 2018.
    1. Root H, Larsen A, Komosa M, Al-Azri F, Li R, Bazett-Jones DP, Stephen Meyn M. FANCD2 limits BLM-dependent telomere instability in the alternative lengthening of telomeres pathway. Hum Mol Genet 2016; 25: 3255–3268.
    1. Sarkar J, Liu Y. Fanconi anemia proteins in telomere maintenance. DNA Repair (Amst) 2016; 43: 107–112.
    1. Pilsworth JA, Cochrane DR, Xia Z, Aubert G, Färkkilä AEM, Horlings HM, Yanagida S, Yang W, Lim JLP, Wang YK, Bashashati A, Keul J, Wong A, Norris K, Brucker SY, Taran FA, Krämer B, Staebler A, van Meurs H, Oliva E, Shah SP, Kommoss S, Kommoss F, Gilks CB, Baird DM, Huntsman DG. TERT promoter mutation in adult granulosa cell tumor of the ovary. Mod Pathol 2018; 31: 1107–1115.
    1. Butts S, Riethman H, Ratcliffe S, Shaunik A, Coutifaris C, Barnhart K. Correlation of telomere length and telomerase activity with occult ovarian insufficiency. J Clin Endocrinol Metab 2009; 94: 4835–4843.
    1. Li Y, Deng B, Ouyang N, Yuan P, Zheng L, Wang W. Telomere length is short in PCOS and oral contraceptive does not affect the telomerase activity in granulosa cells of patients with PCOS. J Assist Reprod Genet 2017; 34: 849–859.
    1. Vitek W, Hoeger K, Legro RS. Treatment strategies for infertile women with polycystic ovary syndrome. Minerva Ginecol 2016; 68: 450–457.
    1. Li Q, Du J, Feng R, Xu Y, Wang H, Sang Q, Xing Q, Zhao X, Jin L, He L, Wang L. A possible new mechanism in the pathophysiology of polycystic ovary syndrome (PCOS): the discovery that leukocyte telomere length is strongly associated with PCOS. J Clin Endocrinol Metab 2014; 99: E234–E240.
    1. Wei D, Xie J, Yin B, Hao H, Song X, Liu Q, Zhang C, Sun Y. Significantly lengthened telomere in granulosa cells from women with polycystic ovarian syndrome (PCOS). J Assist Reprod Genet 2017; 34: 861–866.
    1. Pedroso DC, Miranda-Furtado CL, Kogure GS, Meola J, Okuka M, Silva C, Calado RT, Ferriani RA, Keefe DL, dos Reis RM. Inflammatory biomarkers and telomere length in women with polycystic ovary syndrome. Fertil Steril 2015; 103: 542–7.e2.
    1. Kalyan S, Patel MS, Kingwell E, Côté HCF, Liu D, Prior JC. Competing factors link to bone health in polycystic ovary syndrome: chronic low-grade inflammation takes a toll. Sci Rep 2017; 7: 3432.
    1. Wang C, Shen F, Zhu Y, Fang Y, Lu S. Telomeric repeat-containing RNA (TERRA) related to polycystic ovary syndrome (PCOS). Clin Endocrinol (Oxf) 2017; 86: 552–559.
    1. Calado RT, Yewdell WT, Wilkerson KL, Regal JA, Kajigaya S, Stratakis CA, Young NS. Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells. Blood 2009; 114: 2236–2243.
    1. Zhou C, Steplowski TA, Dickens HK, Malloy KM, Gehrig PA, Boggess JF, Bae-Jump VL. Estrogen induction of telomerase activity through regulation of the mitogen-activated protein kinase (MAPK) dependent pathway in human endometrial cancer cells. PLoS One 2013; 8: e55730.
    1. Jankowska K. Premature ovarian failure. Przegl Menopauz 2017; 16: 51–56.
    1. Kinugawa C, Murakami T, Okamura K, Yajima A. Telomerase activity in normal ovaries and premature ovarian failure. Tohoku J Exp Med 2000; 190: 231–238.

Source: PubMed

3
Prenumerera