Modulation of matrix metalloproteinase secretion by adenosine A3 receptor in preeclamptic villous explants

The impairment of trophoblast invasion associated with preeclampsia may involve matrix metalloproteinase (MMP). Adenosine A3 receptors expression in trophoblast is upregulated in preeclampsia. This study was designed to determine if A3 receptors modulate MMP secretion in villous explants from preeclamptic pregnancies. Villous explants from normal and preeclamptic pregnancies were cultured at 20% and 3% oxygen. There were significantly increased A3 receptor and reduced MMP-2/-9 expression at low oxygen level in normal and preeclamptic explants. Interestingly, in preeclamptic explants, after high oxygen culture, the expression of MMP-2/-9 were recovered to almost same level of those in normal explants. Treatment of preeclamptic explants with A3 receptor agonist in low oxygen level resulted in an enhanced expression of MMP-2/-9 in a time- and dose-dependent manner. In summary, this study indicates that trophoblastic adenosine A3 receptors are 1) modulated by oxygen tension, and 2) regulate MMP-2/-9 expression.