CONICET | Buscador de Institutos y Recursos Humanos

Abstract: Pregnancies carried by women with chronic hypertension are at increased risk of superimposedpreeclampsia, but the placental pathways involved in disease progression remain poorlyunderstood. In this study, we used the stroke-prone spontaneously hypertensive rat (SHRSP) modelto investigate the placental mechanisms promoting superimposed preeclampsia, with focus on cellularstress and its influence on galectin?glycan circuits. Our analysis revealed that SHRSP placentasare characterized by a sustained activation of the cellular stress response, displaying significantlyincreased levels of markers of lipid peroxidation (i.e., thiobarbituric acid reactive substances(TBARS)) and protein nitration and defective antioxidant enzyme expression as early as gestationday 14 (which marks disease onset). Further, lectin profiling showed that such redox imbalance wasassociated with marked alterations of the placental glycocode, including a prominent decrease ofcore 1 O-glycan expression in trophoblasts and increased decidual levels of sialylation in SHRSPplacentas. We also observed significant changes in the expression of galectins 1, 3 and 9 with pregnancyprogression, highlighting the important role of the galectin signature as dynamic interpretersof placental microenvironmental challenges. Collectively, our findings uncover a new role for theglycoredox balance in the pathogenesis of superimposed preeclampsia representing a promisingtarget for interventions in hypertensive disorders of pregnancy.