Our research work has established that there is minimal inflammation in the myometrium with the onset of labour. Rather, the decidua which lines between the muscle of the womb and the placenta is inflamed, suggesting that changes in this tissue may be responsible for the onset of term labour.
Our ongoing work is studying the changes in inflammatory cell number and function in the decidua. Not surprisingly, inflammation of the myometrium was found in cases of preterm labour, caused by infection. It was also present, rather unexpectedly, in twin and unexplained preterm labour.
Understanding why inflammation occurred in twin and unexplained preterm labour is one of our major goals.
Physiologically, progesterone is essential for the initiation and maintenance of pregnancy, but its mechanism of action is not known.
Our work shows that progesterone represses the activity of a transcription factor AP-1, which drives inflammation. Most existing evidence suggest that progesterone acts by changing the expression of genes, particularly those which drive the onset of labour.
We have found that progesterone can also alter protein function modifying their structure. Our ongoing work explores the mechanisms used by progesterone to alter protein function.
Cyclic adenosine monophosphate (cAMP)
This key intracellular second messenger mediates smooth muscle relaxation in the airways and gastrointestinal tract.
Our work has shown that cAMP uses different second messenger systems as pregnancy advances and labour starts, changing its action from one which promotes myometrial relaxation to one which drives myometrial contractions.
Our current work is investigating why the cAMP effector pathways change as labour starts and how we can manipulate their expression to control the onset of labour.