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 Sep;25(9):2316-27. doi: 10.1093/humrep/deq180. Epub 2010 Jul 15.

Abstract

Background: Sister chromatid cohesion is essential for ordered chromosome segregation at mitosis and meiosis. This is carried out by cohesin complexes, comprising four proteins, which seem to form a ring-like complex. Data from animal models suggest that loss of sister chromatid cohesion may be involved in age-related non-disjunction in human oocytes. Here, we describe the distribution of cohesins throughout meiosis in human oocytes.

Methods: We used immunofluorescence in human oocytes at different meiotic stages to detect cohesin subunits REC8, STAG3, SMC1 beta and SMC3, [also synaptonemal complex (SC) protein 3 and shugoshin 1]. Samples from euploid fetuses and adult women were collected, and 51 metaphase I (MI) and 113 metaphase II (MII) oocytes analyzed. SMC1 beta transcript levels were quantified in 85 maturing germinal vesicle (GV) oocytes from 34 women aged 19-43 years by real-time PCR.

Results: At prophase I, cohesin subunits REC8, STAG3, SMC1 beta and SMC3 overlapped with the lateral element of the SC. Short cohesin fibers are observed in the oocyte nucleus during dictyate arrest. All four subunits are observed at centromeres and along chromosomal arms, except at chiasmata, at MI and are present at centromeric domains from anaphase I to MII. SMC1 beta transcripts were detected (with high inter-sample variability) in GV oocytes but no correlation between SMC1 beta mRNA levels and age was found.

Conclusions: The dynamics of cohesins REC8, STAG3, SMC1 beta and SMC3 suggest their participation in sister chromatid cohesion throughout the whole meiotic process in human oocytes. Our data do not support the view that decreased levels of SMC1 beta gene expression in older women are involved in age-related non-disjunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Nucleus / metabolism
  • Centromere / metabolism
  • Chondroitin Sulfate Proteoglycans / metabolism*
  • Chromatids / genetics
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosome Aberrations*
  • Cohesins
  • DNA-Binding Proteins
  • Female
  • Fetus
  • Humans
  • Meiosis*
  • Nuclear Proteins / metabolism*
  • Oocytes* / chemistry
  • Oocytes* / metabolism
  • RNA, Messenger / metabolism
  • Synaptonemal Complex / metabolism
  • Young Adult

Substances

  • Cell Cycle Proteins
  • Chondroitin Sulfate Proteoglycans
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Nuclear Proteins
  • REC8 protein, human
  • RNA, Messenger
  • SGO1 protein, human
  • SMC3 protein, human
  • STAG3 protein, human
  • SYCP3 protein, human
  • structural maintenance of chromosome protein 1