Implantation and Miscarriage
Professor Jan Brosens
Our laboratory has had a long-standing interest in the mechanisms of normal and abnormal endometrial development and its relevance to implantation failure, miscarriage and other pregnancy disorders such as pre-eclampsia and fetal growth restriction.
After ovulation, the rise in progesterone levels will trigger the activation of various gene sets in the endometrium (lining of the womb). These genes are essential for implantation of the embryo and the subsequently formation of the placenta. These effects of progesterone are mediated by the progesterone receptors that are present in the nuclei of endometrial cells.
We are currently investigating how progesterone manages to control diverse gene programmes that regulate endometrial differentiation, cell death, and resistance to cellular stress. Our focus lies on identifying nuclear and cytoplasmic factors that modulate the activity of activated progesterone receptor. To date, we have identified several transcription factors that modify progesterone receptor actions in human endometrium through physical and functional interactions.
These fundamental studies are complemented by translational investigations aimed at identifying clinically useful markers for the prediction of early pregnancy failure. Endometrial samples obtained from distinct patient groups are analysed using a candidate gene approach, gene arrays, and proteomics. In addition, abnormal hormonal responses in the human endometrium also cause various gynaecological diseases, such as endometriosis and endometrial cancer. We have ongoing studies on identifying and validating new therapeutic targets for the treatment of these common reproductive disorders.