Fetal-maternal interface impedance parallels local NADPH oxidase related superoxide production

Abstract

Blood flow assessment employing Doppler techniques is a useful procedure in pregnancy evaluation, as it may predict pregnancy disorders coursing with increased uterine vascular impedance, as pre-eclampsia. While the local causes are unknown, emphasis has been put on reactive oxygen species (ROS) excessive production. As NADPH oxidase (NOX) is a ROS generator, it is hypothesized that combining Doppler assessment with NOX activity might provide useful knowledge on placental bed disorders underlying mechanisms. A prospective longitudinal study was performed in 19 normal course, singleton pregnancies. Fetal aortic isthmus (AoI) and maternal uterine arteries (UtA) pulsatility index (PI) were recorded at two time points: 20-22 and 40-41 weeks, just before elective Cesarean section. In addition, placenta and placental bed biopsies were performed immediately after fetal extraction. NOX activity was evaluated using a dihydroethidium-based fluorescence method and associations to PI values were studied with Spearman correlations. A clustering of pregnancies coursing with higher and lower PI values was shown, which correlated strongly with placental bed NOX activity, but less consistently with placental tissue. The study provides evidence favoring that placental bed NOX activity parallels UtA PI enhancement and suggests that an excess in oxidation underlies the development of pregnancy disorders coursing with enhanced UtA impedance.

Keywords: Aortic isthmus; Doppler; NADPH oxidase; Oxidative stress; Pulsatility index; Uterine artery.

Graphical abstract

Fig. 1

Doppler flow velocity waveforms obtained from the fetal aortic isthmus (panel A) and maternal uterine artery (panel B). panel A: The aortic Isthmus (AoI) is the segment of the aorta located between the origin of the left subclavian artery and the connection of the ductus arteriosus to the descending aorta (*). Under physiological conditions, the direction of flow in the AoI is forward during the entire cardiac cycle. panel B: With the advent of color Doppler, the precise localization of the uterine arteries became feasible; (+) notch, abnormal waveform demonstrating increased impedance and early diastolic notch; (—) notch, normal pregnant waveform.

Fig. 2

Placental and placental bed biopsies. (A) Placenta, central maternal surface (1); (B) placental bed (2).

Fig. 3

Plots of the sample values of DHE conversion against AoI-PI and UtA-PI measurements, at the first (1) and second (2) time points, in the placenta and in the placental bed (respectively, left and right columns).

Fig. 4

Panel A+C: individual time profiles of the AoI-PI and UtA-PI (left-hand side) and the two identified clusters, denoted by A and B; all curves in red belong to the A cluster whereas all curves in green belong to the B cluster. Panel B + D: boxplot of placental bed and placental DHE-conversion in each of the clusters found for the AoI-PI and UtA-PI time trajectories.