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

SZPILBARG N; RECA A; CASTRO PARODI M; MARTÍNEZ N,; DAMIANO A

Mar del Plata

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

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 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 have previously reported that the expression of aquaporins (AQPs) is altered. AQPs are involved not only in several physiological processes but also in multiple and diverse clinical dysfunctions. In other tissues, it has been 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 significantly reduced 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 believed to be a potent stimulus for trophoblast apoptosis. Although apoptosis increases progressively throughout pregnancy, it is exacerbated in preeclamptic placentas. Recently, we have established that intermittent hypoxia alters placental AQPs expression and increases 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.