Introduction: Chronic hypertension is an important risk factor for preeclampsia, increasing the prevalence of the disease to 15-25% in pregnant women. Unfortunately there are no known treatments for this disease aside from inducing delivery of the fetus. Nonetheless, several studies have found exercise training to have a protective effect on the risk of developing preeclampsia.
Objectives: To determine the mechanisms implicated in the preventive effect of exercise training on preeclampsia, by focusing on the placenta.
Methods: Double transgenic mice, overexpressing both human renin and angiotensinogen (R(+)/A(+)), were used to investigate the effect of exercise training on an animal model of preeclampsia superimposed on chronic hypertension. Mice were placed in cages with free access to an exercise wheel 4 weeks prior to and during pregnancy. At gestational day 18, mice were sacrificed and their organs were collected. Real time PCR and Western Blot were performed to evaluate placental genes and proteins, respectively. Circulating sFlt-1(soluble Fms-like tyrosine kinase-1) levels were investigated by ELISA. Placental alterations were assessed by histology and immunohistochemistry, while blood pressure was measured by radiotelemetry.
Results: Sedentary R(+)/A(+) mice presented with significantly greater placental pathology, which was normalized with exercise training. This was characterized by a normalization of cytokeratin and histone H3 protein expression, thereby restoring placental development, specifically looking at trophoblasts and trophoblast giant cells, respectively. This exercise training effect appears to normalize placental growth primarily by promoting angiogenesis and development. Indeed, a pro-angiogenic shift could be detected which was characterized by an increase in placental growth factor gene expression, along with a decrease in sFlt-1 gene expression, which produced a decrease in circulating sFlt-1. Sedentary R(+)/A(+) mice also presented with a significant increase in VEGF protein, which was significantly decreased with exercise. Of interest, since it has been observed to be decreased with preeclampsia, insulin regulated aminopeptidase (IRAP) gene expression was significantly increased in the trained transgenic mice. Finally, exercise training prevented the increase in blood pressure normally observed at the end of gestation in sedentary R(+)A(+) mice.
Conclusion: Exercise training both before and during gestation appears to promote placental growth and development by producing a pro-angiogenic placental environment. Put together, along with the lack in blood pressure increase, these factors may be responsible for preventing the development of preeclampsia in our animal model of preeclampsia superimposed on chronic hypertension. Identifying the mechanisms implicated in exercise-induced preeclampsia risk reduction will be critical to improve preeclampsia prophylaxis.
Copyright © 2012. Published by Elsevier B.V.