Julie L. Lavoie, PhD
Professor and École de kinésiologie et des sciences de l'activité physique of Université de Montréal.
PE is diagnosed after 20 weeks of gestation with the onset of hypertension (systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg) and proteinuria (≥300 mg/24 h). Chronic hypertensive women have a 20-25% risk of developing PE (known as preeclampsia superimposed on chronic hypertension; PESCH). The molecular mechanisms underlying the development of PE are still misunderstood and premature delivery of the foetus is the only treatment available. The renin-angiotensin system (RAS) is postulated to be implicated in the development of PE.
My group has characterized a novel mouse model of PESC. Indeed, mice which overexpress both human angiotensinogen and renin (R+A+), which are hypertensive at baseline, develop spontaneously PESCH-like features as their blood pressure increases, and they develop proteinuria during their pregnancy. This is associated with an increase in AT1 receptor and decrease MasR and ACE2 in placenta and aorta. These modulations may contribute to increase the sensitivity to Ang II as well as decrease both production and sensitivity to Ang 1-7.
While exercise training is well known for its health benefits in the general population, it has also been shown to improve pregnancy outcome during normal gestation. We have recently demonstrated that exercise training can also prevent the occurrence of preeclampsia in mouse models of the disease. Moreover, we have found that the change in RAS observed in the PESCH mouse model can be reduced by exercise training, as we observe an increase in MasR and decrease in AT1 receptor in placenta and aorta. Overall, our project aims at identifying markers of PESCH development and their timing of appearance to allow an earlier diagnostic in patients. We also wish to evaluate the therapeutic potential of both ExT and Ang 1-7 administration in the context of PESCH.
Interestingly, in our recently characterized model of preeclampsia superimposed on chronic hypertension, mice that overexpress both human renin and angiotensinogen (R+A+), we observed that it normalised litter size, which was significantly decreased in the sedentary transgenic mice. Therefore, whereas hypertension or RAS seem to have a negative impact on fertility, exercise training could potentially improve fertility in this model. We therefore wish to test the hypothesis that exercise training restores fertility by modifying the process of ovulation and/or embryo implantation in the R+A+ mice.