Wellcome Centre for Cell Biology

Age-dependent loss of cohesion protection in human oocytes

Marston Lab - Current Biology



Mihalas, B.P., Pieper, G.H., Aboelenain, M., Munro, L., Srsen, V., Currie, C.E., Kelly, D.A., Hartshorne, G.M., Telfer, E.E., McAinsh, A.D., Anderson, R.A., and Marston, A.L.


Two images of Cells from published paper
Human fertility declines with maternal age due to aneuploidy affecting the oocyte. Mihalas et al., use super-resolution microscopy in human oocytes and provide evidence that age-dependent loss of the SGO2 cohesin protector protein could contribute to this phenomenon.

Summary of Paper by Eleanor Casey

Human eggs (oocytes) are made by a unique cell division called meiosis. Errors in meiosis can result in oocytes inheriting the wrong number of chromosomes, a condition known as aneuploidy. Aneuploid oocytes result in infertility, miscarriage, and chromosomal disorders such as Downs Syndrome. As women age, the instances of aneuploidy are known to increase significantly. This is thought to be due to links between sister chromosomes becoming weaker due to deterioration of a protein called cohesin, although the biological process underlying cohesin weakening is unknown. In this study, Mihalas and colleagues investigate the role of a cohesin protector protein, shugoshin 2 (SGO2), in preserving sister chromatid cohesion in young and aged human oocytes. Through super resolution imaging of whole oocytes in meiotic metaphase I, the authors observe SGO2 “cupping” the centromere and pericentromere and forming a bridge between the sister chromosomes. In the aged oocytes, the bridge structure was frequently absent, and in these cells an increased distance between sister kinetochore and incidences of aneuploidy in metaphase II were observed. To test if the presence of SGO2 is important for correct cohesion of sister chromatids, the authors inhibited the SGO2 loader kinase Mps1. When Mps1 was inhibited in young oocytes, the incidence of chromosome missegregation and aneuploidy was increased in metaphase II. From these findings the authors concluded that SGO2 is important to maintain cohesion between the chromosomes in meiosis I. Incorrect localization of SGO2 due to aging or drug inhibition can lead to increased incidences of aneuploidy in meiosis II.


Related Links

Journal URL

Marston Lab Website