Fetoplacental arteriolar dysfunction in placentas of HIV-exposed, small for gestational age birthweight neonates.

Abstract

Objectives: Individuals with HIV are more likely to deliver small-for-gestational-age (SGA) neonates. We evaluated the associations between fetoplacental arteriolar function and HIV-exposure and SGA.

Design: Case-control study of fetoplacental arteriolar function from placentas with/without HIV exposure and with/without SGA birthweight delivered between 36 and 41 weeks of gestation.

Methods: Fetoplacental arterioles were harvested from the intervillous space of fresh placental specimens. We assessed arteriolar function by myograph. We measured dose-dependent contraction to U-46,619 (a thromboxane-prostanoid receptor agonist), endothelin (ET-1), as well as relaxation to AdipoRon (ApR, an adiponectin receptor agonist). ET-1-induced reactive oxygen species (ROS) were measured by DHE fluorescence and ApR-induced nitric oxide (NO) activity by DAF-FM fluorescence using a RatioMaster system. Comparisons across groups were determined using two-way ANOVA.

Results: We analyzed specimens from 9 placentas of HIV-unexposed appropriate for gestational age (AGA)-birthweight neonates, 6 placentas of HIV-unexposed SGA neonates, 11 placentas of HIV-exposed AGA neonates, and 4 placentas of HIV-exposed SGA neonates. Contractions to ET-1 and U-46 619 were greater in placentas with HIV-exposure or of SGA neonates compared to AGA controls, and greatest in the setting of both HIV-exposure and SGA. Impaired arteriolar relaxation to ApR was associated with HIV-exposure, SGA, and combined HIV-exposure with SGA. Likewise, ApR-induced NO was decreased and ET-1-induced ROS was increased with HIV-exposure and SGA.

Conclusions: Fetoplacental arteriolar relaxation was impaired and contraction was enhanced among placentas of HIV-exposed and SGA neonates.