Advertisement

Age-associated alterations in the micromechanical properties of chromosomes in the mammalian egg

  • Jessica E. Hornick
  • Francesca E. Duncan
  • Mingxuan Sun
  • Ryo Kawamura
  • John F. Marko
  • Teresa K. WoodruffEmail author
Gamete Biology

Abstract

Purpose

The incidence of aneuploidy in eggs from women of advanced reproductive age can exceed 60 %, making the mammalian egg a unique model system to study the mechanisms of chromosome segregation errors.

Methods

Here we applied a novel biophysical chromosome stretching approach to quantify mechanical stiffness of meiotic chromosomes in the mammalian egg and then documented how these properties changed in a mouse model of physiologic reproductive aging.

Results

We found significant differences in chromosome micromechanics, and thus in higher order chromosome structure, coincident with advanced reproductive age, a time that is also unequivocally associated with an increase in egg aneuploidy.

Conclusions

These findings have important implications for both reproductive and cancer biology where aneuploidy plays a central role in aging related disease states.

Keywords

Reproductive aging Meiosis Mammalian Chromosome Micromechanics 

Notes

Acknowledgments

This work was supported by grants from the National Institutes of Health (U54HD041857 to TKW and U54HD076188, U54CA143869 and R01GM105847 to JFM) and the National Science Foundation (NSF) (MCB-1022117 and DMR-1206868 to JFM).

References

  1. 1.
    Jones KT, Lane SIR. Molecular causes of aneuploidy in mammalian eggs. Development. 2013;140(18):3719–30. doi: 10.1242/dev.090589.CrossRefPubMedGoogle Scholar
  2. 2.
    Duncan FE, Hornick JE, Lampson MA, Schultz RM, Shea LD, Woodruff TK. Chromosome cohesion decreases in human eggs with advanced maternal age. Aging Cell. 2012;11(6):1121–4. doi: 10.1111/j.1474-9726.2012.00866.x.CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Hassold T, Hunt P. Maternal age and chromosomally abnormal pregnancies: what we know and what we wish we knew. Curr Opin Pediatr. 2009;21(6):703–8. doi: 10.1097/MOP.0b013e328332c6ab.CrossRefPubMedCentralPubMedGoogle Scholar
  4. 4.
    Hunt P, Hassold T. Female meiosis: coming unglued with age. Cur Biol. 2010;20(17):R699–702. doi: 10.1016/j.cub.2010.08.011.CrossRefGoogle Scholar
  5. 5.
    Chiang T, Duncan FE, Schindler K, Schultz RM, Lampson MA. Evidence that weakened centromere cohesion is a leading cause of age-related aneuploidy in oocytes. Curr Biol. 2010;20(17):1522–8. doi: 10.1016/j.cub.2010.06.069.CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    Garcia-Cruz R, Brieño MA, Roig I, Grossmann M, Velilla E, Pujol A, et al. Dynamics of cohesin proteins REC8, STAG3, SMC1 beta and SMC3 are consistent with a role in sister chromatid cohesion during meiosis in human oocytes. Hum Reprod. 2010;25(9):2316–27. doi: 10.1093/humrep/deq180.CrossRefPubMedGoogle Scholar
  7. 7.
    Vialard F, Lombroso R, Bergere M, Gomes DM, Hammoud I, Bailly M, et al. Oocyte aneuploidy mechanisms are different in two situations of increased chromosomal risk: older patients and patients with recurrent implantation failure after in vitro fertilization. Fertil Steril. 2007;87(6):1333–9. doi: 10.1016/j.fertnstert.2006.11.042.CrossRefPubMedGoogle Scholar
  8. 8.
    Kawamura R, Pope LH, Christensen MO, Sun M, Terekhova K, Boege F, et al. Mitotic chromosomes are constrained by topoisomerase II-sensitive DNA entanglements. J Cell Biol. 2010;188(5):653–63. doi: 10.1083/jcb.200910085.CrossRefPubMedCentralPubMedGoogle Scholar
  9. 9.
    Marko JF. Micromechanical studies of mitotic chromosomes. Chromosom Res Int J Mol Supramol Evol Asp Chromosom Biol. 2008;16(3):469–97. doi: 10.1007/s10577-008-1233-7.CrossRefGoogle Scholar
  10. 10.
    Sun M, Kawamura R, Marko JF. Micromechanics of human mitotic chromosomes. Phys Biol. 2011;8(1):015003. doi: 10.1088/1478-3975/8/1/015003.CrossRefPubMedCentralPubMedGoogle Scholar
  11. 11.
    Merriman JA, Jennings PC, McLaughlin EA, Jones KT. Effect of aging on superovulation efficiency, aneuploidy rates, and sister chromatid cohesion in mice aged up to 15 months. Biol Reprod. 2012;86(2):49. doi: 10.1095/biolreprod.111.095711.CrossRefPubMedGoogle Scholar
  12. 12.
    Yun Y, Lane SI, Jones KT. Premature dyad separation in meiosis II is the major segregation error with maternal age in mouse oocytes. Development. 2014;141(1):199–208. doi: 10.1242/dev.100206.CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Cho AS, Jeon SM, Kim MJ, Yeo J, Seo KI, Choi MS, et al. Chlorogenic acid exhibits anti-obesity property and improves lipid metabolism in high-fat diet-induced-obese mice. Food Chem Toxicol Int J Publ Br Ind Biol Res Assoc. 2010;48(3):937–43. doi: 10.1016/j.fct.2010.01.003.CrossRefGoogle Scholar
  14. 14.
    Poirier MG, Marko JF. Micromechanical studies of mitotic chromosomes. Curr Top Dev Biol. 2003;55:75–141.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Jessica E. Hornick
    • 1
    • 2
  • Francesca E. Duncan
    • 1
    • 2
    • 6
  • Mingxuan Sun
    • 3
    • 7
  • Ryo Kawamura
    • 4
    • 8
  • John F. Marko
    • 3
    • 4
    • 5
  • Teresa K. Woodruff
    • 1
    • 2
    Email author
  1. 1.Department of Obstetrics and Gynecology, Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  2. 2.Center for Reproductive ScienceNorthwestern UniversityEvanstonUSA
  3. 3.Department of Molecular BiosciencesNorthwestern UniversityEvanstonUSA
  4. 4.Department of Physics and AstronomyNorthwestern UniversityEvanstonUSA
  5. 5.National Cancer Institute Physical Science and Oncology CenterNorthwestern UniversityEvanstonUSA
  6. 6.Department of Anatomy and Cell BiologyThe University of Kansas Medical CenterKansas CityUSA
  7. 7.QB3 InstituteUniversity of CaliforniaBerkeleyUSA
  8. 8.Department of PhysicsNational University of SingaporeSingaporeSingapore

Personalised recommendations