Altered Levels of Mitochondrial DNA Are Associated with Female Age, Aneuploidy, and Provide an Independent Measure of Embryonic Implantation Potential

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Mitochondria are small membrane-enclosed structures and are found inside the cells of the body. Mitochondria actively participate in cellular life, and their main function is to generate energy which is used by the cell. For this reason mitochondria are considered as the powerhouses of cells. Unlike other cellular organelles, mitochondria contain their own DNA (mtDNA). MtDNA carries important genetic information concerning cellular metabolism and the generation of energy. It has been suggested that mitochondria and mtDNA could be of significance during early embryo development. Our work confirms this hypothesis. Specifically, our findings implicate mitochondria and their genome in female reproductive aging and the generation of embryonic chromosome abnormalities. Importantly, we describe a direct relationship between mtDNA quantity and the potential of an embryo to successfully become a baby. We propose that assessment of mtDNA quantity could be a novel way of identifying embryos with the highest ability to lead to healthy pregnancies and live births.

Vyšlo v časopise: Altered Levels of Mitochondrial DNA Are Associated with Female Age, Aneuploidy, and Provide an Independent Measure of Embryonic Implantation Potential. PLoS Genet 11(6): e32767. doi:10.1371/journal.pgen.1005241
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005241

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1. May-Panloup P, Chrétien MF, Jacques C, Vasseur C, Malthièry Y, et al. (2005) Low oocyte mitochondrial DNA content in ovarian insufficiency. Hum Reprod 20: 593–597. 15608038

2. Dumollard R, Carroll J, Duchen MR, Campbell K, Swann K (2009) Mitochondrial function and redox state in mammalian embryos. Semin Cell Dev Biol 20: 346–353. 19530278

3. St John JC, Facucho-Oliveira J, Jiang Y, Kelly R, Salah R (2010) Mitochondrial DNA transmission, replication and inheritance: a journey from the gamete through the embryo and into offspring and embryonic stem cells. Hum Reprod Update 16: 488–509. doi: 10.1093/humupd/dmq002 20231166

4. Bentov Y, Casper RF (2013) The aging oocyte—can mitochondrial function be improved? Fertil Steril 99: 18–22. doi: 10.1016/j.fertnstert.2012.11.031 23273985

5. Tilly JL, Sinclair DA (2013) Germline energetics, aging, and female infertility. Cell Metab 17: 838–850. doi: 10.1016/j.cmet.2013.05.007 23747243

6. Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, et al. (1981) Sequence and organization of the human mitochondrial genome. Nature 290: 457–465. 7219534

7. Palmer CS, Osellame LD, Stojanovski D, Ryan MT (2011) The regulation of mitochondrial morphology: intricate mechanisms and dynamic machinery. Cell Signal 23: 1534–1545. doi: 10.1016/j.cellsig.2011.05.021 21683788

8. Eichenlaub-Ritter U, Wieczorek M, Lüke S, Seidel T (2011) Age related changes in mitochondrial function and new approaches to study redox regulation in mammalian oocytes in response to age or maturation conditions. Mitochondrion 11: 783–796. doi: 10.1016/j.mito.2010.08.011 20817047

9. Chen X, Prosser R, Simonetti S, Sadlock J, Jagiello G, et al. (1995) Rearranged mitochondrial genomes are present in human oocytes. Am J Hum Genet 57: 239–247. 7668249

10. Motta PM, Nottola SA, Makabe S, Heyn R (2000). Mitochondrial morphology in human fetal and adult germ cells. Hum Reprod 15: 129–147. 11041520

11. Cummins JM (2000) Fertilization and elimination of the paternal mitochondrial genome. Hum. Reprod 15: 92–101. 11041517

12. Steuerwald N, Barritt JA, Adler R, Malter H, Schimmel T, et al. (2000) Quantification of mtDNA in single oocytes, polar bodies and subcellular components by real-time rapid cycle fluorescence monitored PCR. Zygote 8: 209–215. 11014500

13. Reynier P, May-Panloup P, Chrétien MF, Morgan CJ, Jean M, et al. (2001) Mitochondrial DNA content affects the fertilizability of human oocytes. Mol Hum Reprod 7: 425–429. 11331664

14. Barritt JA, Kokot M, Cohen J, Steuerwald N, Brenner CA (2002) Quantification of human ooplasmic mitochondria. Reprod Biomed Online 4: 243–247. 12709274

15. Lin DP, Huang CC, Wu HM, Cheng TC, Chen CI, et al. (2004) Comparison of mitochondrial DNA contents in human embryos with good or poor morphology at the 8-cell stage. Fertil Steril 81: 73–79. 14711547

16. Chan CC, Liu VW, Lau EY, Yeung WS, Ng EH, et al. (2005) Mitochondrial DNA content and 4977 bp deletion in unfertilized oocytes. Mol Hum Reprod 11: 843–846. 16421213

17. Van Blerkom J, Davis PW, Lee J (1995) ATP content of human oocytes and developmental potential and outcome after in-vitro fertilization and embryo transfer. Hum Reprod 10: 415–424. 7769073

18. Fragouli E, Alfarawati S, Spath K, Jaroudi S, Sarasa J, et al. (2013). The origin and impact of embryonic aneuploidy. Hum Genet 132: 1001–1013. doi: 10.1007/s00439-013-1309-0 23620267

19. Van Blerkom J (2011) Mitochondrial function in the human oocyte and embryo and their role in developmental competence. Mitochondrion 11: 797–813. doi: 10.1016/j.mito.2010.09.012 20933103

20. Houghton F (2006) Energy metabolism of the inner cell mass and trophectoderm of the mouse blastocyst. Differentiation 74: 11–18. 16466396

21. Barritt JA, Cohen J, Brenner CA (2000) Mitochondrial DNA point mutation in human oocytes is associated with maternal age. Reprod Biomed Online 1: 96–100. 12804188

22. Konstantinidis M, Alfarawati S, Hurd D, Paolucci M, Shovelton J, et al. (2014) Simultaneous assessment of aneuploidy, polymorphisms, and mitochondrial DNA content in human polar bodies and embryos with the use of a novel microarray platform. Fertil Steril: in press.

23. Narita A (1995) Endogenous factors affecting sterility in oocytes of aged animals. Jap J Fertil Steril 40: 57–65.

24. Duran HE, Simsek-Duran F, Oehninger SC, Jones HW Jr, Castora (2011) The association of reproductive senescence with mitochondrial quantity, function, and DNA integrity in human oocytes at different stages of maturation. Fertil Steril 96: 384–388. doi: 10.1016/j.fertnstert.2011.05.056 21683351

25. Piko L, Taylor KD (1987) Amounts of mitochondrial DNA and abundance of some mitochondrial gene transcripts in early mouse embryos. Dev Biol 123: 364–374. 2443405

26. Simsek-Duran F, Li F, Ford W, Swanson RJ, Jones HW Jr, et al. (2009) The effect of aging on the metabolic function and structure of mitochondria in hamster oocytes. FASEB J 855: 10.

27. Monnot S, Samuels DC, Hesters L, Frydman N, Gigarel N, et al. (2013) Mutation dependance of the mitochondrial DNA copy number in the first stages of human embryogenesis. Hum Mol Genet 22: 1867–1872. doi: 10.1093/hmg/ddt040 23390135

28. Hsieh RH, Au HK, Yeh TS, Chang SJ, Cheng YF, et al. (2004) Decreased expression of mitochondrial genes in human unfertilized oocytes and arrested embryos. Fertil Steril 81: 912–918. 15019829

29. Hsieh RH, Tsai NM, Au HK, Chang SJ, Wei YH, et al. (2002) Multiple rearrangements of mitochondrial DNA in unfertilized human oocytes. Fertil Steril 77: 1012–1017. 12009360

30. Fragouli E, Alfarawati S, Daphnis DD, Goodall NN, Mania A, et al. (2011) Cytogenetic analysis of human blastocysts with the use of FISH, CGH and aCGH: scientific data and technical evaluation. Hum Reprod 26:480–490 doi: 10.1093/humrep/deq344 21147821

31. Wells D, Kaur K, Grifo J, Glassner M, Taylor JC, et al. (2014) Clinical utilisation of a rapid low-pass whole genome sequencing technique for the diagnosis of aneuploidy in human embryos prior to implantation. J Med Genet 51: 553–562. doi: 10.1136/jmedgenet-2014-102497 25031024

32. Zhang X, Wu XQ, Lu S, Guo YL, Ma X (2006) Deficit of mitochondria- derived ATP during oxidative stress impairs mouse MII oocyte spindles. Cell Res 16: 841–850. 16983401

33. Choi WJ, Banerjee J, Falcone T, Bena J, Agarwal A, et al. (2007) Oxidative stress and tumor necrosis factor-induced alterations in metaphase II mouse oocyte spindle structure. Fertil Steril 88:1220–1231. 17601599

34. Johnson MT, Freeman EA, Gardner DK, Hunt PA (2007) Oxidative metabolism of pyruvate is required for meiotic maturation of murine oocytes in vivo. Biol Reprod 77: 2–8. 17314311

35. Yu Y, Dumollard R, Rossbach A, Lai FA, Swann K (2010) Redistribution of mitochondria leads to bursts of ATP production during spontaneous mouse oocyte maturation. Journal of Cellular Physiology 224: 672–680. doi: 10.1002/jcp.22171 20578238

36. Wang Q, Ratchford AM, Chi MM, Schoeller E, Frolova A, et al. (2009) Maternal diabetes causes mitochondrial dysfunction and meiotic defects in murine oocytes. Mol Endocrinol 23: 1603–1612. doi: 10.1210/me.2009-0033 19574447

37. Wilding M, De Placido G, DeMatteo L, Marino M, Alviggi C, et al. (2003) Chaotic mosaicism in human preimplantation embryos is correlated with a low mitochondrial membrane potential, Fertil Steril 79: 340–346. 12568843

38. Capalbo A, Wright G, Elliott T, Ubaldi FM, Rienzi L et al. (2013) FISH reanalysis of inner cell mass and trophectoderm samples of previously array-CGH screened blastocysts shows high accuracy of diagnosis and no major diagnostic impact of mosaicism at the blastocyst stage. Hum Reprod 28: 2298–2307. doi: 10.1093/humrep/det245 23739221

39. Leese HJ (2002) Quiet please, do not disturb: a hypothesis of embryo metabolism and viability. Bioessays 24: 845–849. 12210521

40. Harton GL, Munné S, Surrey M, Grifo J, Kaplan B, McCulloh DH, et al. (2013) Diminished effect of maternal age on implantation after preimplantation genetic diagnosis with array comparative genomic hybridization. Fertil Steril 100: 1695–1670 doi: 10.1016/j.fertnstert.2013.07.2002 24034939

41. Magli MC, Montag M, Koster M, Muzi L, Geraedts J, et al. (2011) Polar body array CGH for prediction of the status of the corresponding oocyte. Part II: technical aspects. Hum Reprod 26:3181–3185. doi: 10.1093/humrep/der295 21908464

42. Gutierrez-Mateo C, Colls P, Sanchez-Garcıa J, Escudero T, Prates R, et al. (2011) Validation of microarray comparative genomic hybridization for comprehensive chromosome analysis of embryos. Fertil Steril 95:953–958. doi: 10.1016/j.fertnstert.2010.09.010 20971462

43. Christopikou D, Tsorva E, Economou K, Shelley P, Davies S, et al. (2013) Polar body analysis by array comparative genomic hybridization accurately predicts aneuploidies of maternal meiotic origin in cleavage stage embryos of women of advanced maternal age. Hum Reprod 28: 1426–1434. doi: 10.1093/humrep/det053 23477909

44. Mertzanidou A, Spits C, Nguyen HT, Van de Velde H, Sermon K (2013) Evolution of aneuploidy up to Day 4 of human preimplantation development. Hum Reprod 28: 1716–1724. doi: 10.1093/humrep/det079 23526301

45. Fregel R, Almeida M, Betancor E, Suarez NM, Pestano J (2011) Reliable nuclear and mitochondrial DNA quantification for low copy number and degraded forensic samples. Forensic Science International: Genetics Supplement Series 3: e303–e304.

46. Li H, Durbin R (2009) Fast and accurate short read alignment with Burrows—Wheeler transform. Bioinformatics 25: 1754–1760. doi: 10.1093/bioinformatics/btp324 19451168

47. Raczy C, Petrovski R, Saunders CT, Chorny I, Kruglyak S et al. (2013) Isaac: ultra-fast whole-genome secondary analysis on Illumina sequencing platforms. Bioinformatics 29:2041–2043 doi: 10.1093/bioinformatics/btt314 23736529

48. Quinlan AR, Hall IM (2010) BEDTools: A flexible suite of utilities for comparing genomic features, Bioinformatics 26: 841–842. doi: 10.1093/bioinformatics/btq033 20110278

49. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, et al. (2009) The Sequence alignment/map (SAM) format and SAMtools. Bioinformatics 25: 2078–2079. doi: 10.1093/bioinformatics/btp352 19505943

50. Baslan T, Kendall J, Rodgers L, Cox H, Riggs M, et al. (2012) Genome-wide copy number analysis of single cells. Nat Protoc 7: 1024–1041. doi: 10.1038/nprot.2012.039 22555242

51. Zhidkov I, Nagar T, Mishmar D, Rubin E (2011) MitoBamAnnotator: A web-based tool for detecting and annotating heteroplasmy in human mitochondrial DNA sequences. Mitochondrion 11: 924–928. doi: 10.1016/j.mito.2011.08.005 21875693

52. Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative CT method. Nat Protoc 3: 1101–1108. 18546601