Preterm birth (PTB) is the single largest cause of death in infants and young children. 40-45% of all PTBs follow spontaneous labour with intact membranes and 25-30% are associated with preterm premature rupture of membranes. The rate of PTB is significantly higher in male infants, particularly those that are born very preterm.
We have demonstrated that the decidual renin-angiotensin system may play a critical role in inhibiting inflammation and maintaining the integrity of the fetal membranes during pregnancy, and that sex-specific alterations in the intrauterine RAS might contribute to the increased risk of PTB in male babies.
We have shown that women carrying female fetuses have high levels of expression of decidual prorenin at term. Decidua from ‘female’ pregnancies also have greater expression of the anti-inflammatory angiotensin (Ang)-(1-7) pathway, than decidua from ‘male’ pregnancies, and have lower levels of the pro-inflammatory Ang II pathway. We propose that in ‘female’ pregnancies, the very high levels of decidual prorenin drive the anti-inflammatory Ang-(1-7) pathway, thus reducing the likelihood of PTB.
In addition, the high levels of prorenin produced by the decidua in ‘female’ pregnancies are able to diffuse into the amnion and bind to the PRR. We postulate that the PRR/prorenin interaction possibly through both angiotensin dependent and independent pathways stimulates the production of ECM proteins, inhibits ECM degradation and prevents apoptosis, thus strengthening the amnion.
Thus control of the inflammatory signature and the integrity of the fetal membranes prior to parturition may partly depend on the sexually determined activity of the decidual and amniotic renin angiotensin system pathways.