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Journal of Assisted Reproduction and Genetics logoLink to Journal of Assisted Reproduction and Genetics
. 2004 Mar;21(3):79–83. doi: 10.1023/B:JARG.0000027018.02425.15

Why Do Older Women Have Poor Implantation Rates? A Possible Role of the Mitochondria

Ana Karina Bartmann 1,, Gustavo Salata Romão 2, Ester da Silveira Ramos 2, Rui Alberto Ferriani 2
PMCID: PMC3455407  PMID: 15202735

Abstract

Mitochondria are organelles responsible for oxidative phosphorylation, the main energy source for all eukaryotic cells. In oocytes and embryos, it seems that mitochondria provide sufficient energy for fecundation by supporting spindle formation during meiosis II, and for implantation. Since mitochondria are inherited from mother to child, it is important that oocyte mitochondria should be intact. Older women seem to have more mitochondrial DNA mutations, which can be responsible for poor implantation and aneuploidy, two conditions that occur more often in this group. In the present report we propose a new model to explain why older women have poor implantation rates.

Keywords: Aneuploidy, mitochondria, older women, poor implantation

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References

  • 1.Boettcher PJ, Kuhn MT, Freeman AE. Impacts of cytoplasmic inheritance on genetic evaluations. J Day Sci. 1996;79:663–675. doi: 10.3168/jds.S0022-0302(96)76412-3. [DOI] [PubMed] [Google Scholar]
  • 2.McGinnis KT, Diamond MP, Dozortsev DI. Simultaneous evaluation of morphology, mitochondrial mass, mitochondrial function and genetic complement in the preimplantation embryo. Fertil Steril. 2001;76:S240. [Google Scholar]
  • 3.Anderson AS, Banker AT, Barrel BG, de Bruijin MHL, Coulson AR, Drouin J. Sequence and organization of the human mitochondrial genome. Nature. 1981;290:457–465. doi: 10.1038/290457a0. [DOI] [PubMed] [Google Scholar]
  • 4.Ashley MV, Laipis PJ, Hauswirth WW. Rapid segregation of heteroplasmic bovine mitochondria. Nucleic Acids Res. 1989;17:7325–7331. doi: 10.1093/nar/17.18.7325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Smith LC, Bordignon V, Garcia JM, Meirelles FV. Mitochondrial genotype segregation and effects during mammalian development: Applications to biotechnology. Theriogenology. 2000;53:35–46. doi: 10.1016/s0093-691x(99)00238-1. [DOI] [PubMed] [Google Scholar]
  • 6.Birky CW. Relaxed and stringent genomes: Why cytoplasmic genes don't obey Mendel's laws. J Hered. 1994;85:355–365. [Google Scholar]
  • 7.Bendall KE, Macaulay VA, Baker J., Sykes BC. Heteroplasmic point mutations in the human mtDNA control region. Am J Genet. 1996;59:1276–1287. [PMC free article] [PubMed] [Google Scholar]
  • 8.Marchington DR, Macaulay V, Hartshorne GM, Barlow D, Poulton J. Evidence from human oocytes for a genetic bottleneck in a mtDNA disease. Am J Hum Genet. 1998;63:769–775. doi: 10.1086/302009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Lee SH, Han JH, Kim HH, Lee SM, Chung MK, Cha KY. Semiquantitative analysis of common deletion in mitochondrial DNA of single human oocytes. Fertil Steril. 2000;74:S194. [Google Scholar]
  • 10.Barritt JA, Cohen J, Brenner CA. The age related mitochondrial DNA control region point mutation (t414g) in human oocytes. Fertil Steril. 2000;74:S3. [Google Scholar]
  • 11.Yesodi V, Yaron Y, Azem F, Lessing JB, Amit A. Mitochondrial DNA mutations in human oocytes: Correlation with IVF outcome. Fertil Steril. 2000;74:S81. doi: 10.1023/A:1014439529813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Sathananthan AH, Trounson AO. Mitochondrial morphology during preimplantation human embryogenesis. Hum Reprod. 2000;15:148–159. doi: 10.1093/humrep/15.suppl_2.148. [DOI] [PubMed] [Google Scholar]
  • 13.Munné S, Alikani M, Tomkin G, Grifo J, Cohen J. Embryo morphology, developmental rates, and maternal age are correlated with chromosome abnormalities. Fertil Steril. 1995;64:382–391. [PubMed] [Google Scholar]
  • 14.Dailey T, Dale B, Cohen J, Munné S. Association between nondisjunction and maternal age in meiosis II human oocytes. Am J Hum Genet. 1996;59:176–184. [PMC free article] [PubMed] [Google Scholar]
  • 15.Warburton D. The effect of maternal age on the frequency of trisomy: Change in meiosis or in utero selection? In: Hassold TJ, Epstein CJ, editors. Molecular and Cytogenetic Studies of Non-Dysjunction. New York: Liss; 1989. pp. 165–181. [PubMed] [Google Scholar]
  • 16.Salamanca-Gómez F. Reduced ovarian complement, premature ovarian failure and Down syndrome. Am J Med Genet. 2001;99:168–169. doi: 10.1002/1096-8628(2000)9999:999<00::aid-ajmg1131>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  • 17.Van Montfrans JM, Lambalk CB, van Hooff MHA, van Vugt JMG. Are elevated FSH concentrations in the pre-conceptional period a risk factor for Down's syndrome pregnancies? Hum Reprod. 2001;16:1270–1273. doi: 10.1093/humrep/16.6.1270. [DOI] [PubMed] [Google Scholar]
  • 18.Nasseri A, Mukherjee T, Grifo JA, Noyes N, Krey L, Coperman AB. Elevated day 3 serum follicle stimulating hormone and/or estradiol may predict fetal aneuploidy. Fertil Steril. 1999;71:715–718. doi: 10.1016/s0015-0282(98)00525-1. [DOI] [PubMed] [Google Scholar]
  • 19.Freeman SB, Quanhe Y, Allran K, Taft LF, Sherman SL. Women with a reduced ovarian complement may have an increased risk for a child with Down Syndrome. Am J Hum Genet. 2001;66:1680–1683. doi: 10.1086/302907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Winston N, Johnson M, Pickering S, Braude P. Parthogenetic activation and development of fresh and aged human oocytes. Fertil Steril. 1991;56:904–912. [PubMed] [Google Scholar]
  • 21.Battaglia DE, Goodwin P, Klein NA. Influence of maternal age on meiotic spindle assembly in oocytes from naturally cycling women. Hum Reprod. 1996;11:2217–2222. doi: 10.1093/oxfordjournals.humrep.a019080. [DOI] [PubMed] [Google Scholar]
  • 22.Takeuchi T, Gong J, Veeck LL, Rosenwaks Z, Palermo GD. Preliminary findings in germinal vesicle transplantation of immature human oocytes. Hum Reprod. 2001;16:730–736. doi: 10.1093/humrep/16.4.730. [DOI] [PubMed] [Google Scholar]
  • 23.Cohen J, Scott R, Alikani M. Ooplasmic transfer in mature human oocytes. Mol Hum Reprod. 1998;4:269–280. doi: 10.1093/molehr/4.3.269. [DOI] [PubMed] [Google Scholar]
  • 24.Barritt JA, Brenner CA, Malter HE, Cohen J. Mitochondria in human offspring derived from ooplasmic transplantation. Hum Reprod. 2001;16:513–516. doi: 10.1093/humrep/16.3.513. [DOI] [PubMed] [Google Scholar]
  • 25.Hsieh R, Tsai N, Au H, Chang S, Cheng Y, Tzeng C. Multiple rearrangements of mitochondrial DNA and defective oxidative phosphorylation gene expression in unfertilized human oocytes. Fertil Steril. 2001;76:S8. doi: 10.1016/s0015-0282(02)02994-1. [DOI] [PubMed] [Google Scholar]
  • 26.Wilding MG, Dale B, De Placido G. Confocal measurements of mitochondria activity during human pre-implantation embryo development. Fertil Steril. 2001;76:S205. [Google Scholar]
  • 27.Magli MC, Jones GM, Gras L, Gianaroli L, Korman I, Trounson AO. Chromosome mosaicism in day 3 aneuploid embryos that develop to morphologically normal blastocysts in vitro. Hum Reprod. 2000;15:1781–1786. doi: 10.1093/humrep/15.8.1781. [DOI] [PubMed] [Google Scholar]
  • 28.Wang WH, Meng L, Hackett RJ, Odenbourg R, Keefe DL. The spindle observation and its relation with fertilization after intracytoplasmic sperm injection in living human oocytes. Fertil Steril. 2001;75:348–353. doi: 10.1016/s0015-0282(00)01692-7. [DOI] [PubMed] [Google Scholar]
  • 29.Wang WH, Meng L, Hackett RJ, Keefe DL. Development ability of human oocytes with or without birefringent spindles imaged by Polscope before insemination. Hum Reprod. 2001;16:1464–1468. doi: 10.1093/humrep/16.7.1464. [DOI] [PubMed] [Google Scholar]
  • 30.Pickering SJ, Braude PR, Johnson MH, Cant A, Currie J. Transient cooling to room temperature can cause irreversible disruption of meiotic spindle in the human oocyte. Fertil Steril. 1990;54:702–708. doi: 10.1016/s0015-0282(16)53644-9. [DOI] [PubMed] [Google Scholar]
  • 31.Schon EA. Mitochondrial genetics and disease. TIBS. 2000;25:555–560. doi: 10.1016/s0968-0004(00)01688-1. [DOI] [PubMed] [Google Scholar]
  • 32.Sevidei S. Mitochondrial encephalomyopathies: Gene mutation. Neuromuscul Disord. 2001;11:690–695. doi: 10.1016/s0960-8966(01)00265-6. [DOI] [PubMed] [Google Scholar]
  • 33.Han J, Lee S, Jun H, Park J, Kwak I, Cha K. Quantification of mitochondrial DNA and mitochondrial tRNA mutation at position 3243 in Korean gestational diabetes mellitus. Fertil Steril. 2001;76:S158. [Google Scholar]
  • 34.Jones GM, Trounson AO, Lolatgis N, Wood C. Factors affecting the success of human blastocyst development and pregnancy following in vitro fertilization and embryo transfer. Fertil Steril. 1998;70:1022–1029. doi: 10.1016/s0015-0282(98)00342-2. [DOI] [PubMed] [Google Scholar]
  • 35.Liu H, Zhang J, Krey LC, Grifo JA. In-vitro development of mouse zygotes following reconstruction by sequential transfer of germinal vesicles and haploid pronuclei. Hum Reprod. 2000;15:1997–2002. doi: 10.1093/humrep/15.9.1997. [DOI] [PubMed] [Google Scholar]
  • 36.Cummins JM. Cytoplasmic inheritance and its implications for animal biotechnology. Theriogenology. 2001;55:1381–1399. doi: 10.1016/s0093-691x(01)00489-7. [DOI] [PubMed] [Google Scholar]
  • 37.Ménézo Y, Barak Y. Comparison between day-2 embryos obtained either from ICSI or resulting from short insemination IVF: Influence of maternal age. Hum Reprod. 2000;15:1776–1780. doi: 10.1093/humrep/15.8.1776. [DOI] [PubMed] [Google Scholar]

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