Is age-related increase of chromosome segregation errors in mammalian oocytes caused by cohesin deterioration?

Abstract

Background: Mammalian oocytes initiate meiosis in fetal ovary and are arrested at dictyate stage in prophase I for a long period. It is known that incidence of chromosome segregation errors in oocytes increases with advancing age, but the molecular mechanism underlying this phenomenon has not been clarified. Methods: Cohesin, a multi-subunit protein complex, mediates sister chromatid cohesion in both mitosis and meiosis. In this review, molecular basis of meiotic chromosome cohesion and segregation is summarized. Further, the relationship between chromosome segregation errors and cohesin deterioration in aged oocytes is discussed. Results: Recent studies show that chromosome-associated cohesin decreases in an age-dependent manner in mouse oocytes. Furthermore, conditional knockout or activation of cohesin in oocytes indicates that only the cohesin expressed before premeiotic S phase can establish and maintain sister chromatic cohesion and that cohesin does not turnover during the dictyate arrest. Conclusion: In mice, the accumulating evidence suggests that deterioration of cohesin due to the lack of turnover during dictyate arrest is one of the major causes of chromosome segregation errors in aged oocytes. However, whether the same is true in human remains elusive since even the deterioration of cohesin during dictyate arrest has not been demonstrated in human oocytes.