ABSTRACT
The use of contrast agents as signal enhancers during ultrasound improves visualization and the diagnostic utility of this technology in medical imaging. Although widely used in many disciplines, contrast ultrasound is not routinely implemented in obstetrics, largely due to safety concerns of administered agents for pregnant women and the limited number of studies that address this issue. Here the microbubble characteristics that make them beneficial for enhancement of the blood pool and the quantification of real-time imaging are reviewed. Literature from pregnant animal model studies and safety assessments are detailed, and the potential for contrast-enhanced ultrasound to provide clinically relevant data and benefit our understanding of early placental development and detection of placental dysfunction is discussed.
Subject(s)
Contrast Media/chemistry , Placentation/physiology , Ultrasonography , Animals , Female , Humans , Microbubbles , Models, Animal , Pregnancy , Vascular Remodeling/physiologyABSTRACT
Current methods for placental tissue collection assess a delivered organ without direct functional correlates; therefore, the four-quadrant biopsy protocol utilized by many researchers may provide reasonable representation of tissue across a large organ, and offer a snapshot for molecular analysis of the placenta. However, the recent impetus to understand the placenta in real time, and the use of functional imaging to comprehend placental biology, warrants a different sampling approach. Here we present a method to standardize placental tissue collection in a format designed to facilitate correlation of in vivo function with ex vivo assessments. Additionally, we draw comparisons to the quadrant biopsy regimen, and highlight a pathological case of placental infarction detected by in utero imaging.
Subject(s)
Biopsy/methods , Magnetic Resonance Imaging/methods , Placenta/diagnostic imaging , Biopsy/standards , Dissection/methods , Female , Humans , Placenta/pathology , Pregnancy , Proteins/analysisABSTRACT
Prenatal alcohol exposure (PAE), like other pregnancy complications, can result in placental insufficiency and fetal growth restriction, although the linking causal mechanisms are unclear. We previously identified 11 gestationally elevated maternal circulating miRNAs (HEamiRNAs) that predicted infant growth deficits following PAE. Here, we investigated whether these HEamiRNAs contribute to the pathology of PAE, by inhibiting trophoblast epithelial-mesenchymal transition (EMT), a pathway critical for placental development. We now report for the first time that PAE inhibits expression of placental pro-EMT pathway members in both rodents and primates, and that HEamiRNAs collectively, but not individually, mediate placental EMT inhibition. HEamiRNAs collectively, but not individually, also inhibited cell proliferation and the EMT pathway in cultured trophoblasts, while inducing cell stress, and following trophoblast syncytialization, aberrant endocrine maturation. Moreover, a single intravascular administration of the pooled murine-expressed HEamiRNAs, to pregnant mice, decreased placental and fetal growth and inhibited the expression of pro-EMT transcripts in the placenta. Our data suggest that HEamiRNAs collectively interfere with placental development, contributing to the pathology of PAE, and perhaps also, to other causes of fetal growth restriction.
