Wellbeing of Women

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Restaging the spindle assembly checkpoint in female mammalian meiosis I
Homer HA, McDougall A, Levasseur M, Herbert M Cell Cycle 2005 May;4:650–653.

Restaging the spindle assembly checkpoint in female mammalian meiosis I

Homer HA, McDougall A, Levasseur M, Herbert M
Cell Cycle 2005 May;4:650–653.

During the formation of the human egg in the ovaries, the chromosomes in the egg-precursor cell (or oocyte) undergo two sequential divisions so that when they are combined with genetic material from the sperm at fertilization, the resulting embryo has a full compliment of chromosomes. This process is termed meiosis, and is achieved through a complex sequence of events that involves the formation of a scaffolding-like structure of microtubules called the spindle inside the oocyte. The spindle is essential for accurate and equal division of the chromosomes. Accurate division of the chromosomes during meiosis is critical if the embryo is to develop correctly and the baby is to thrive.

In this review, the authors discuss the cellular machinery and proteins present in mammalian oocytes that enable meiosis to occur. The authors focus on a group of proteins called the Spindle Assembly Checkpoint (SAC), which is a proof-reading network responsible for ensuring that the chromosomes divide accurately. These proteins (including Mad2 and BubR1) delay division of the chromosomes until they are anchored properly onto the spindle.

In mice, reduced levels of the protein Mad2 speed up meiosis in the oocyte, supporting a role for this protein in providing chromosomes with sufficient time in which to become properly attached to the spindle. Importantly, the faster completion of meiosis associated with reduced levels of Mad2 culminates in chromosome division errors, highlighting the importance of these proteins in ensuring accurate division.

In humans, the first stage of meiosis in women is highly prone to division errors and is also susceptible to the aging process. Ensuring that meiosis occurs at a rate compatible with accurate chromosome segregation combined with an efficient system for disposing of faulty embryos that will be unable to develop into healthy babies are the body’s natural defence systems. A major proportion of division errors occur during meiosis in the oocytes of older women. It is thought that these errors may be due to reduced levels of the Mad2 protein in the oocytes of older women.

Further studies are required to determine the roles of BubR1 and other SAC proteins in human oocytes in order to develop future therapeutic options for improving human reproductive outcome.

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