Abstract
Preeclampsia is a pregnancy-related hypertensive disorder accounting for 14% of global maternal deaths annually. Preeclampsia — maternal hypertension and proteinuria — is promoted by placental ischemia resulting from reduced uteroplacental perfusion. Here, we assess longitudinal changes in placental oxygenation during preeclampsia using spectral photoacoustic imaging. Spectral photoacoustic images were acquired of the placenta of normal pregnant (NP) and preeclamptic reduced uterine perfusion pressure (RUPP) Sprague Dawley rats on gestational days (GD) 14, 16, and 18, corresponding to mid- to late gestation (n = 10 per cohort). Two days after implementation of the RUPP surgical model, placental oxygen saturation decreased 12% in comparison with NP. Proteinuria was determined from a 24-hour urine collection prior to imaging on GD18. Blood pressure measurements were obtained on GD18 after imaging. Placental hypoxia in the RUPP was confirmed with histological staining for hypoxia-inducible factor (HIF)-1α, a cellular transcription regulator which responds to local oxygen levels. Using in vivo, longitudinal imaging methods we determined that the placenta in the reduced uterine perfusion pressure rat model of preeclampsia is hypoxic, and that this hypoxia is maintained through late gestation. Future work will utilize these methods to assess the impact of novel therapeutics on placental ischemia and the progression of preeclampsia.
Highlights
Pregnancy-related hypertensive disorders, including preeclampsia, account for 14% of global maternal deaths annually[1]
reduced uterine perfusion pressure (RUPP) animals show the clinical symptoms of preeclampsia during late gestation along with increased levels of hypoxia inducible factor (HIF)-1α, a cellular transcription regulator which responds to local oxygen levels to control vascularization and angiogenesis[2]
We found that the placental environment was hypoxic two days after the RUPP procedure was implemented and that hypoxia was maintained through gestational days (GD) 18 in comparison with normal pregnant animals
Summary
Pregnancy-related hypertensive disorders, including preeclampsia, account for 14% of global maternal deaths annually[1]. Placental ischemia can be assessed by measuring blood oxygen levels through cordocentesis This highly invasive procedure poses risks to fetal well-being. Photoacoustic imaging is a hybrid light and sound imaging modality capable of providing high spatial and temporal resolution images In recent years, it has been utilized for a range of biomedical imaging applications including ophthalmology and oncology[4,5]. Spectral photoacoustic imaging has been used to detect placental and fetal oxygen saturation in normal and pathologic pregnancies and to investigate the effect maternal hypoxia and hyperoxygenation have on placental function[7,8]. We demonstrate that spectral photoacoustic imaging can be used to measure placental ischemia in the RUPP model of preeclampsia
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