Telomere DNA Deficiency Is Associated with Development of Human Embryonic Aneuploidy

English version České info

Aneuploidy represents the most prevalent form of genetic instability found in human embryos and is the leading genetic cause of miscarriage and developmental delay in newborns. Telomere DNA deficiency is associated with genomic instability in somatic cells and may play a role in development of aneuploidy commonly found in female germ cells and human embryos. To test this hypothesis, we developed a method capable of quantifying telomere DNA in parallel with 24-chromosome aneuploidy screening from the same oocyte or embryo biopsy. Aneuploid human polar bodies possessed significantly less telomere DNA than euploid polar bodies from sibling oocytes (−3.07 fold, P = 0.016). This indicates that oocytes with telomere DNA deficiency are prone to aneuploidy development during meiosis. Aneuploid embryonic cells also possessed significantly less telomere DNA than euploid embryonic cells at the cleavage stage (−2.60 fold, P = 0.002) but not at the blastocyst stage (−1.18 fold, P = 0.340). The lack of a significant difference at the blastocyst stage was found to be due to telomere DNA normalization between the cleavage and blastocyst stage of embryogenesis and not due to developmental arrest of embryos with short telomeres. Heterogeneity in telomere length within oocytes may provide an opportunity to improve the treatment of infertility through telomere-based selection of oocytes and embryos with reproductive competence.

Vyšlo v časopise: Telomere DNA Deficiency Is Associated with Development of Human Embryonic Aneuploidy. PLoS Genet 7(6): e32767. doi:10.1371/journal.pgen.1002161
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002161

Souhrn

Zdroje

1. HassoldTHuntP 2001 To err (meiotically) is human: the genesis of human aneuploidy. Nature reviews 2 4 280 291

2. TreffNRSuJTaoXLevyBScottRTJr 2010 Accurate single cell 24 chromosome aneuploidy screening using whole genome amplification and single nucleotide polymorphism microarrays. Fertility and sterility 94 6 2017 2021

3. ScottRTJrMillerKAOlivaresRSuJFratterelliJ 2008 Microarray based 24 chromosome preimplantation genetic diagnosis (mPGD) is highly predictive of the reproductive potential of human embryos:a prospective blinded non-selection trial. Fertility and sterility 90 1 22

4. ScottRTJrTaoXTaylorDFerryKTreffN 2010 A prospective randomized controlled trial demonstrating significantly increased clinical pregnancy rates following 24 chromosome aneuploidy screening: biopsy and analysis on day 5 with fresh transfer. Fertility and sterility 94 4 S2

5. TreffNRSuJTaoXFrattarelliJLMillerKA 2008 Characterization of the source of human embryonic aneuploidy using microarray-based 24 chromosome preimplantation genetic diagnosis (mPGD) and aneuploid chromosome fingerprinting. Fertility and sterility 90 Supplement 1 S37 S37

6. LambNEShermanSLHassoldTJ 2005 Effect of meiotic recombination on the production of aneuploid gametes in humans. Cytogenetic and genome research 111 3–4 250 255

7. HendersonSAEdwardsRG 1968 Chiasma frequency and maternal age in mammals. Nature 218 5136 22 28

8. KeefeDLMarquardKLiuL 2006 The telomere theory of reproductive senescence in women. Current opinion in obstetrics & gynecology 18 3 280 285

9. McClintockB 1939 The Behavior in Successive Nuclear Divisions of a Chromosome Broken at Meiosis. Proc Natl Acad Sci USA 25 8 405 416

10. BlackburnEH 2000 Telomere states and cell fates. Nature 408 6808 53 56

11. LiuLBlascoMAKeefeDL 2002 Requirement of functional telomeres for metaphase chromosome alignments and integrity of meiotic spindles. EMBO reports 3 3 230 234

12. LiuLFrancoSSpyropoulosBMoensPBBlascoMA 2004 Irregular telomeres impair meiotic synapsis and recombination in mice. Proc Natl Acad Sci USA 101 17 6496 6501

13. LiuLBlascoMTrimarchiJKeefeD 2002 An essential role for functional telomeres in mouse germ cells during fertilization and early development. Developmental biology 249 1 74 84

14. CawthonRM 2009 Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic acids research 37 3 e21

15. GanYEngelkeKJBrownCAAuJL 2001 Telomere amount and length assay. Pharmaceutical research 18 12 1655 1659

16. CristofariGLingnerJ 2006 Telomere length homeostasis requires that telomerase levels are limiting. The EMBO journal 25 3 565 574

17. KangMRMullerMTChungIK 2004 Telomeric DNA damage by topoisomerase I. A possible mechanism for cell killing by camptothecin. The Journal of biological chemistry 279 13 12535 12541

18. KapoorVTelfordWG 2004 Telomere length measurement by fluorescence in situ hybridization and flow cytometry. Methods in molecular biology (Clifton, NJ 263 385 398

19. AkiyamaMYamadaOKandaNAkitaSKawanoT 2002 Telomerase overexpression in K562 leukemia cells protects against apoptosis by serum deprivation and double-stranded DNA break inducing agents, but not against DNA synthesis inhibitors. Cancer letters 178 2 187 197

20. GardnerDKSchoolcraftWB 1999 In vitro culture of human blastocysts. JansenRMortimerD Towards reproductive certainty: infertility and genetics beyond Carnforth Parthenon Press 378 388

21. LiuLBaileySMOkukaMMunozPLiC 2007 Telomere lengthening early in development. Nature cell biology 9 12 1436 1441

22. SchaetzleinSLucas-HahnALemmeEKuesWADorschM 2004 Telomere length is reset during early mammalian embryogenesis. Proc Natl Acad Sci USA 101 21 8034 8038

23. TurnerSWongHPRaiJHartshorneGM 2010 Telomere lengths in human oocytes, cleavage stage embryos and blastocysts. Molecular human reproduction 16 9 685 694

24. TreffNRSuJTaoXNorthropLEScottRTJr 2010 Single Cell Whole Genome Amplification Technique Impacts the Accuracy of SNP Microarray Based Genotyping and Copy Number Analyses. Molecular human reproduction

25. KeefeDLFrancoSLiuLTrimarchiJCaoB 2005 Telomere length predicts embryo fragmentation after in vitro fertilization in women–toward a telomere theory of reproductive aging in women. American journal of obstetrics and gynecology 192 4 1256 1260

26. VannesteEVoetTLe CaignecCAmpeMKoningsP 2009 Chromosome instability is common in human cleavage-stage embryos. Nature medicine 15 5 577 583

27. GabrielASHassoldTJThornhillARAffaraNAHandysideAH 2011 An algorithm for determining the origin of trisomy and the positions of chiasmata from SNP genotype data. Chromosome Res

28. TreffNRSuJTaoXKatz-JaffeMSchoolcraftWB 2009 Characterizing the Nature of Meiotic Errors: PSSC is the Principal Meiotic Error in Human Oocytes and May Correct During the 2nd Meiotic Division and Result in the Birth of a Healthy Infant. Fertility and sterility 92 Supplement S25

29. BarlowALHultenMA 1996 Combined immunocytogenetic and molecular cytogenetic analysis of meiosis I human spermatocytes. Chromosome Res 4 8 562 573

30. NicklasJABuelE 2006 Simultaneous determination of total human and male DNA using a duplex real-time PCR assay. Journal of forensic sciences 51 5 1005 1015

31. SchmittgenTDLivakKJ 2008 Analyzing real-time PCR data by the comparative CT method. NatProtocols 3 6 1101 1108

32. TreffNRSuJKasabwalaNMillerKALevyB 2010 Robust embryo identification using first polar body single nucleotide polymorphism (SNP) microarray-based DNA fingerprinting. Fertility and sterility 93 7 2453 2455

33. TreffNRSuJTaoXMillerKALevyB 2009 A novel single-cell DNA fingerprinting method successfully distinguishes sibling human embryos. Fertility and sterility 94 2 477 484

34. PinheiroJBatesDDebRoySSarkarD R Development Core Team 2010 Linear and Nonlinear Mixed Effects Models. R Package version 31 97

35. R Development Core Team 2009 R: A language and environment for statistical computing