Wellbeing of Women

McDougall

Homer H, McDougall A, Levasseur M, Murdoch A, Herbert M

Mad2 is required for inhibiting securing and cyclin B degradation following spindle depolymerisation in meiosis I mouse oocytes

Homer H, McDougall A, Levasseur M, Murdoch A, Herbert M
Reproduction 2006;130(6):829-43

Data suggest that rapid completion of meiosis is associated with division errors thereby increasing the potential for miscarriage and birth defects. It is now known that meiosis is regulated by a number of proteins – including Mad2, securin and cyclin B – which ensure that this process proceeds at a controlled pace to prevent such errors from occurring. During chromosome division, the presence of securin and cyclin B maintain the spindle until the chromosomes have aligned accurately and are able to divide correctly. Once this has been achieved, levels of the two proteins decline, the spindle breaks down and the cell enters the next stage of meiosis accompanied by reassembly of the spindle.

In previous investigations, the researchers in the current study showed that Mad2 is important for the regulation of securin and cyclin B levels within the egg-producing cell and, thus, the prevention of division errors [Genes Dev. 2005 Jan 15;19(2):202-7]. In this study, they extended their investigation of the role of Mad2 in meiosis by depleting levels of the protein and administering spindle poisons to egg-producing cells in the laboratory.

The researchers showed that administration of spindle poisons and subsequent depolymerisation of the spindle caused the destruction of securin and cyclin B to be inhibited, with Mad2 being an essential element in this response. This prevented the progression of meiosis and averted the risk of inaccurate division of the chromosomes. Conversely, they also showed that levels of securin and cyclin B drop prematurely in Mad2-depleted cells, increasing the risk that meiosis could proceed with errors.

These data suggest a vital role for Mad2 in ensuring that meiosis proceeds correctly. It is hoped that greater understanding of the roles of proteins such as Mad2 in meiosis may help to reduce rates of miscarriage and birth defects in the future, particularly in older mothers in whom Mad2 levels are reduced and such problems are more common.