FOLLICULOGENESIS (Provided by John Eppig) .

Considerable progress was made about 10 years ago when it was realised that the receptors regulate the activity of target genes by recruiting cofactor proteins. These proteins are responsible for remodelling the structure of genes so that they are expressed at different levels ultimately determining the function of the cell. We have been studying the role of these cofactors by generating mice that lack the corresponding gene and exhibit developmental or physiological changes in the absence of the cofactor.

We have now found that a repressor for hormone receptors is essential for ovulation and for controlling lipid and carbohydrate levels. Our work has emphasised the importance of preventing the expression of gene networks which would otherwise disrupt the function of a tissue. In ovaries lacking the corepressor there are approximately 500 genes whose expression is abnormally increased. Many of these genes are involved in cell-matrix and cell-cell interactions. This results in the failure of the cumulus-oocyte complex to expand and the mature follicle to rupture with the result that the oocyte is retained in the follicle.

Ovulatory dysfunction is a major cause of female infertility. The failure of the mice to ovulate resembles 'luteinised unruptured follicle' syndrome often associated with infertility in women. Studies of the anovulatory phenotype in mice should provide insights into ovulatory dysfunction in women. It may also be possible to target the repressor to prevent ovulation in fertility control

if you wish to donate to this research please click here