ENDOMETRIAL BIOLOGY: 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.
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