Causes and consequences of chromosomal cohesin loss: Novel insights for mechanisms of aging-related oocyte aneuploidy.

Abstract

Female fertility sharply declines from the mid-thirties of their life, mainly due to age-related decreases in oocyte quality and quantity. Among numerous interconnected maternal factors, an increase in the incidence of aneuploidy caused by meiotic errors is a leading cause of oocyte competence decrease. Why advanced maternal age increases the likelihood of chromosome segregation errors in oocytes remains one of the outstanding questions in reproductive and developmental biology, and it is becoming more important as the age at which women have children continues to rise. A better understanding of this question is crucial for developing effective strategies for prophylaxis or therapeutic interventions for infertility. The progressive loss of cohesin, a ring-shaped protein complex with fundamental roles in chromosome cohesion and architecture, has recently been heavily implicated in the increase in oocyte aneuploidy rates during maternal aging. This review discusses the underlying mechanisms of age-related aneuploidy in oocytes. We particularly ask how chromosomal cohesin loss affects the fidelity of oocyte chromosome segregation and examine physiological factors that contribute to this deterioration.