Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, OR 97006, USA.
Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR 97239, USA.
Molecules. 2023 Mar 23;28(7):2894. doi: 10.3390/molecules28072894.
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 (), 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.
全面监测妊娠期间的生理和病理生理过程的能力可以降低母婴发病率和死亡率。对比增强超声（CEUS）是一种利用微泡的声学检测来检查血管空间的无创成像技术。此外，与特定化合物偶联的微泡可以将研究重点放在精确的生理途径上。我们假设磷脂酰丝氨酸微泡（MB-PS）的 CEUS 可用于监测胎盘炎症。我们在恒河猴（）中检验了这一假设，恒河猴是人类胎盘健康的转化和相关动物模型。由于胎盘炎症会影响许多高危妊娠，我们在给予高脂肪饮食（例如，西式饮食，WSD）的怀孕恒河猴中进行了 MB-PS 的 CEUS，同时存在或不存在睾酮（T）以模拟多囊卵巢综合征和不孕的风险增加。我们之前在该模型中证明了胎盘炎症表型，因此，我们将 MB-PS CEUS 信号强度与胎盘炎症标志物：选择素 p 和血管生成素相关联。与对照动物相比，T 暴露增加了胎盘母体侧微循环中的 MB-PS 信号。我们发现 T 增加了胎盘重量并降低了血管生成素 2（ANGPT2）免疫反应性。此外，MB-PS 信号与 ANGPT2 之间存在显著的负相关。这表明 MB-PS 的 CEUS 可用于监测胎盘参数。我们提出，MB-PS 的 CEUS 可以帮助识别有胎盘血管损伤风险的妊娠。
