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

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.