Lactic Acid Transport Mediated by Aquaporin-9: Implications on the Pathophysiology of Preeclampsia.

MEDINA, YOLLYSETH; ACOSTA, LUCAS; REPPETTI, JULIETA; COROMINAS, ANA; BUSTAMANTE, JUANITA; SZPILBARG, NATALIA; DAMIANO, ALICIA ERMELINDA

Frontiers in Physiology

Frontiers

Año: 2021 vol. 12

1664-042X

Aquaporin-9 (AQP9) expression is significantly increased in preeclamptic placentas. Sincefeto-maternal water transfer is not altered in preeclampsia, the main role of AQP9 in humanplacenta is unclear. Given that AQP9 is also a metabolite channel, we aimed to evaluate theparticipation of AQP9 in lactate transfer across the human placenta. Explants from normal termplacentas were cultured in low glucose medium with or without L-lactic acid and in the presenceand absence of AQP9 blockers (0.3mm HgCl2 or 0.5mm Phloretin). Cell viability was assessedby 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and lactatedehydrogenase release. Apoptotic indexes were analyzed by Bax/Bcl-2 ratio and TerminalDeoxynucleotidyltransferase-Mediated dUTP Nick-End Labeling assay. Heavy/large and light/small mitochondrial subpopulations were obtained by differential centrifugation, and AQP9expression was detected by Western blot. We found that apoptosis was induced when placentalexplants were cultured in low glucose medium while the addition of L-lactic acid prevented celldeath. In this condition, AQP9 blocking increased the apoptotic indexes. We also confirmedthe presence of two mitochondrial subpopulations which exhibit different morphologic andmetabolic states. Western blot revealed AQP9 expression only in the heavy/large mitochondrialsubpopulation. This is the first report that shows that AQP9 is expressed in the heavy/largemitochondrial subpopulation of trophoblasts. Thus, AQP9 may meditate not only the lacticacid entrance into the cytosol but also into the mitochondria. Consequently, its lack of functionalityin preeclamptic placentas may impair lactic acid utilization by the placenta, adversely affectingthe survival of the trophoblast cells and enhancing the systemic endothelial dysfunction.