Molecular basis of chromosome segregation and age-associated errors in oocyte meiosis I

Abstract Oocyte meiosis determines chromosomes that are transmitted from the mother to the next generation. The molecular mechanisms underlying meiotic chromosome segregation are organized in distinct chromosomal regions—the core centromere, peri-centromere, and chromosome arms. A common molecular basis for mechanisms operating in these distinct regions is Rec8 cohesin, together with cooperating regulatory pathways. This Review describes Rec8-cohesin-based mechanisms operating in each chromosomal region and discusses how these mechanisms work coordinately to achieve chromosome segregation during meiosis I, focusing primarily on insights from studies using mouse oocytes as a model system. Based on this molecular understanding, it further discusses how age-associated decline of chromosomal Rec8 cohesin can lead to chromosome segregation errors, a major cause of infertility, miscarriage, and congenital disorders.