Utilizing Contrast-Enhanced Ultrasonography with Phosphatidylserine Microbubbles to Detect Placental Inflammation in Rhesus Macaques

Abstract

The ability to comprehensively monitor physiological and detect pathophysiologic processes early during pregnancy can reduce maternal and fetal morbidity and mortality. Contrast-enhanced ultrasound (CEUS) is a non-invasive imaging technology that utilizes the acoustic detection of microbubbles to examine vascular spaces. Furthermore, microbubbles conjugated to specific compounds can focus studies on precise physiological pathways. We hypothesized that CEUS with phosphatidylserine microbubbles (MB-PS) could be employed to monitor placental inflammation. We tested this hypothesis in rhesus macaques (Macaca mulatta), a translational and relevant animal model of human placental health. As placental inflammation impacts many at-risk pregnancies, we performed CEUS with MB-PS in pregnant macaques fed a high-fat diet (e.g., a western-style diet, WSD) in the presence or absence of testosterone (T) to mimic the increased risk of polycystic ovary syndrome and subfertility. We have previously demonstrated a placental inflammation phenotype in this model, and, thus, we related the MB-PS CEUS signal intensity to placental inflammation markers: selectin p and angiopoietins. Testosterone exposure increased the MB-PS signal in the placental microcirculation on the maternal side compared to control animals. We found that T increased placental weight and decreased angiopoietin 2 (ANGPT2) immunoreactivity. Furthermore, a significant inverse correlation was found between MB-PS signal and ANGPT2. This indicated that CEUS with MB-PS can be used to monitor placental parameters. We propose that CEUS with MB-PS could aid in the identification of pregnancies at risk of placental vascular compromise.

Reducing the Risk of Pre-Eclampsia in Women with Polycystic Ovary Syndrome Using a Combination of Pregnancy Screening, Lifestyle, and Medical Management Strategies

“…Women with PE have a heightened inflammatory state with elevated pro-inflammatory cytokines and chemokines, both systemically and in the placenta [ 120 , 160 ]. Studies in rodents and non-human primates have provided evidence of mechanistic links between maternal inflammation and PE [ 120 , 122 ]. Lipopolysaccharide-induced inflammation in pregnant rats showed that inflammation was associated with deficient trophoblast invasion and spiral artery remodeling [ 120 ].…”

“…In addition, inflammation increased the maternal mean arterial pressure and was associated with structural changes in the kidney and proteinuria, as is found in PE [ 120 ]. Wilson et al demonstrated increased syncytiotrophoblast inflammation in a testosterone-induced primate model of PCOS using a novel contrast-enhanced ultrasound technique [ 122 ].…”

“…Many of these physiological processes are known to be involved in the pathophysiologies of both PCOS and PE [3,25]. Wilson [122] Primate model of PCOS Testosterone Syncytiotrophoblast inflammation…”