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.
Subject(s)
Cell Cycle Proteins/metabolism , Chondroitin Sulfate Proteoglycans/metabolism , Chromosomal Proteins, Non-Histone/metabolism , Chromosome Aberrations , Meiosis , Nuclear Proteins/metabolism , Oocytes , Adult , Aging , Cell Cycle Proteins/genetics , Cell Nucleus/metabolism , Centromere/metabolism , Chromatids/genetics , Chromosomal Proteins, Non-Histone/genetics , DNA-Binding Proteins , Female , Fetus , Humans , Oocytes/chemistry , Oocytes/metabolism , RNA, Messenger/metabolism , Synaptonemal Complex/metabolism , Young Adult , CohesinsABSTRACT
It is accepted that recombination errors during human female meiotic prophase have some influence on the origin of trisomy 21. A total of 335 oocytes from four euploid fetuses were analysed by immunofluorescence and fluorescence in-situ hybridization in order to assess the recombination nodules along chromosome 21. Results based on the analysis of recombination points on the bivalent 21 during human female meiosis showed that both number [none (3.70%), one (79.01%) and two (17.29%)1 and distribution (always positioned interstitially on the q-arm) are different in males, ensuring that the two homologues more efficiently remain together until anaphase 1.Therefore, the mainly maternal origin of trisomy 21 appears not be linked to the first stages of oocyte development during fetal life, and this leads to the suggestion that the influence of environmental factors on the segregation of chromosome 21 homologues in later meiotic stages could have a significant role in the predominant maternal origin of trisomy 21.
