Dynamics of cohesin proteins REC8, STAG3, SMC1β and SMC3 are consistent with a role in sister chromatid cohesion during meiosis in human oocytes

BACKGROUND: Sister chromatidcohesion is essential for ordered chromosome segregationat mitosis and meiosis. This is carried out by cohesincomplexes, comprising four proteins, which seem to form a ring-like complex. Data from animal models suggest that loss of sister chromatidcohesion may be involved in age-related non- disjunctionin human oocytes. Here, we describe the distribution of cohesinsthroughout meiosisin human oocytes. METHODS: We used immunofluorescence in human oocytesat different meiotic stages to detect cohesinsubunits REC8, STAG3, SMCIβ and SMC3, [also synaptonemal complex(SC) protein 3 and shugoshin 1]. Samples from euploid fetuses and adult women were collected, and 51 metaphaseI (MI) and 113 metaphase11 (MII) oocytesanalyzed. SMCIβ transcript levels were quantified in 85 maturing germinal vesicle (GV) oocytesfrom 34 women aged 19-43 years by real-time PCR. RESULTS: At prophase I, cohesinsubunits REC8, STAG3, SMC Iβ and SMC3 overlapped with the lateral element of the SC. Short cohesinfibers are observed in the oocytenucleus during dictyatearrest. All four subunits are observed at centromeresand along chromosomal arms, except at chiasmata, at MI and are present at centromericdomains from anaphase1 to MII. SMCIβ transcripts were detected (with high inter-sample variability) in GV oocytesbut no correlation between SMCIβ mRNA levels and age was found. CONCLUSIONS: The dynamics of cohesinsREC8, STAG3, SMCIβ and SMC3 suggest their participation in sister chromatidcohesion throughout the whole meiotic process in human oocytes. Our data do not support the view that decreased levels of SMCIβ gene expression in older women are involved in age-related non- disjunction.