New insights into the role of placental aquaporins and the pathogenesis of preeclampsia

SZPILBARG NATALIA; RECA ALEJANDRA; CASTRO-PARODI MAURICIO; MARTINEZ, NORA; DAMIANO ALICIA E

Mar del Plata

Simposio; VI LatinAmerican Symposium on Maternal-Fetal Interaction & Placenta; 2015

Placenta Association of the Americas- Grupo Latinoamericano de placenta

Preeclampsia is a pregnancy complication characterized by hypertension and proteinuria. Although its etiology is unknown, it is considered as a two-stage disorder. In the first stage, the reduced placental perfusion, in some, but not in all women, could lead to the second stage where the maternal multisystem disorder is established. However, what links both stages is not determined yet. Since the placenta plays a central role in this syndrome, alterations in placental functions may contribute to the pathogenesis of preeclampsia. Accumulated evidence suggests that the expression of a variety of syncytiotrophoblast transporters is reduced or abnormal in preeclamptic placentas. In this regard, we previously reported that the expression of aquaporins (AQPs) is altered. AQPs are not only involved in several physiological processes but also in multiple and diverse clinical dysfunctions. In other tissues, it was proposed that AQPs may participate in cell migration/invasion processes. Therefore, we evaluated the association of AQPs with these events during placentation. Our results showed that inhibition of AQPs reduced significantly the migration and invasion of trophoblast cells. Thus, we proposed that abnormal expression of these proteins might lead to a shallow trophoblast invasion characteristic of preeclamptic placentas. Consequently, placentation takes place under fluctuations of oxygen tension, which are believe to be a potent stimulus for trophoblast apoptosis. Although apoptosis increases progressively throughout pregnancy, it is exacerbated in preeclamptic placentas. Recently, we established that intermittent hypoxia altered placental AQPs expression and increased the apoptosis of the trophoblast. Even more, we found that the blocking of placental AQPs abrogated these processes, suggesting that AQPs may also have a role in apoptosis. In conclusion, we propose that the abnormal expression of placental AQPs, at early stages of pregnancy, may produce failures in placentation, resulting in an increase of trophoblast apotosis which finally triggers the clinical manifestations of preeclampsia.