HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

Review

Mad2 and spindle assembly checkpoint function during meiosis I in mammalian oocytes

H.A. Homer

Newcastle Fertility Centre at Life, BioSciences Centre, International Centre for Life, Times Square, Newcastle upon Tyne, UK and School of Surgical and Reproductive Sciences, The Medical School, Framlington Place, University of Newcastle, Newcastle upon Tyne, UK

Offprint requests to: Dr. Hayden A. Homer, Department of Obstetrics & Gynaecology, Cumberland Infirmary, Carlisle, Cumbria CA2 7HY, UK. email: h.a.homer@ncl.ac.uk


Summary. During mammalian mitosis, a proofreading network called the spindle assembly checkpoint (SAC) is indispensable for ensuring the fidelity of chromosome segregation. An inhibitory SAC signal is deputed to inhibits mitotic cell-cycle progression in response to misaligned chromosomes until such imperfections are rectified thereby ensuring equitable chromosome partitioning to daughter cells. Amongst the cast of SAC proteins, mitotic arrest deficient 2 (Mad2) plays a leading role in transducing the SAC signal. The aneuploidy and cancer predispositions of individuals who harbour genetic mutations in SAC genes emphasise the in vivo significance of this surveillance mechanism. In humans, congenital aneuploidies such as Down’s syndrome demonstrate an exponential increase with advancing female age. Although largely the result of female meiosis I errors, the molecular entities that succumb with age in oocytes remain elusive. Declining oocyte SAC function could plausibly contribute to such errors. Until recently however, convincing evidence for a functional SAC in mammalian oocytes during meiosis I was unforthcoming. Here I review the evidence regarding the SAC in female mammalian meiosis I and how our understanding of this system has evolved in recent years. This review will focus on Mad2 as this is the SAC protein that has been most comprehensively investigated. Histol Histopathol 21, 873-886 (2006)

Key words: Nosdisjunction, Mammals, Oocyte maturation, Homologue disjunction, Aneuploidy