Increased protein O-GlcNAcYLATION in human placentas from hypertensive pregnancies.

Abstract

Introduction: Key proteins involved in placentation are susceptible to O-linked β-N-acetylglucosamine modification (O-GlcNAcylation). Anomalies in protein O-GlcNAcylation have been associated with pathological conditions, including hypertension, and it is known that arterial hypertension negatively impacts placental function. However, the precise impact of protein O-GlcNAcylation on placental function and fetal growth remains unclear in humans. Therefore, the current study aimed to investigate O-GlcNAcylation expression, and its catalytic enzyme O-GlcNAc transferase (OGT), in the placenta of pregnant women suffering from high blood pressure disorders.

Methods: Full-term placental samples were collected and divided into groups of normotensives (n = 11) or hypertensives women (n = 11). Western blotting and immunohistochemistry assessed O-GlcNAc and OGT expressions, and morphological characterization was conducted in all samples.

Results: In the hypertensive group, the maternal age (p = 0.041) was higher, whereas the gestational age (p = 0.004) and the newborn weight (p = 0.032) decreased, compared to the normotensive group. Morphometric analysis showed that the placentas from the hypertensive group displayed altered morphology, which was compatible with placentas from hypertensive mothers. Placental O-GlcNAc (p = 0.029) and OGT (p = 0.048) protein expression were higher in the hypertensive group. Augmented expression of O-GlcNAc was more predominant in the villi but also observed at the decidua.

Discussion: The present study demonstrates augmented protein O-GlcNAcylation and OGT expression in the placenta of pregnant with hypertensive disorders of pregnancy. In the future, the use of banks of placental tissue may be a useful strategy to map and identify candidates for O-GlcNAc modulation, requiring further evaluation.