Faculty of Health Sciences

Introduction: Globally, preeclampsia (PE) complicates an estimated 2-8% of pregnancies and is a leading cause of maternal and fetal morbidity and mortality. Renal injury is closely involved in the pathophysiology of PE and is associated with future risk of kidney disease. Identifying an early biomarker of renal dysfunction is essential for the diagnosis and treatment of PE. Given the clinical and ethical complexities associated with pregnancy studies in humans, animal models provide a more feasible alternative to pregnancy research. Aim: In view of this, this study aimed to determine the physiological and biochemical features of the arginine vasopressin (AVP) induced pregnancy model in the Sprague Dawley rat and to demonstrate nephrotoxicity associated with this model. Methodology: Urine, blood and kidney samples (n = 6 per study group) were collected from female Sprague Dawley rats, based on four study groups, viz., pregnant AVP, pregnant saline, non-pregnant AVP, and non-pregnant saline groups. The AVP rat model was physiologically characterized by evaluating the clinical, biochemical, haematological and fetal parameters across all study groups. Renal injury in AVP-treated rats was histologically determined by haematoxylin and eosin staining, as well as immunolocalizing kidney injury molecule-1 (KIM-1) and podocalyxin in both AVPtreated and untreated kidneys using immunohistochemistry. Ultrastructural changes in AVP-treated rats were determined by transmission electron microscopy. The Multiplex kidney toxicity immunoassay panels were used to determine the urinary concentration of albumin, vascular endothelial growth factor-A, clusterin, cystatin C, beta-2- microglobulin, KIM-1, neutrophil gelatinase-associated lipocalin-2, osteopontin and tissue inhibitor of metalloproteinases-1 in AVP-treated rats. Key findings: Chronic infusion of AVP throughout gestation reproduced the phenotypes viz., increased blood pressure, elevated urinary protein levels and fetal growth restriction, characteristic of human PE development. Immunohistochemical analysis confirm KIM1 immunolocalization in the proximal convoluted tubules of AVP-treated vs. untreated groups. Comparatively, a mild immunolocalization of podocalyxin was observed in the glomeruli of pregnant AVP-treated vs. pregnant untreated rats. Histological and ultrastructural evaluation of the AVP-treated pregnant rats demonstrated several abnormalities including, reduced Bowman’s space, necrosis of tubules and blood vessels, along with podocyte effacement, glomerular basement membrane abnormalities, podocyte nuclear crenations, mitochondrial dysfunction and cytoplasmic lysis consistent with renal injury in PE. Our findings indicate that AVP significantly reduces the urinary levels of vascular endothelial growth factor A and concomitantly up-regulates the urinary expression of clusterin, cystatin C, beta-2-microglobulin, KIM-1, neutrophil gelatinaseassociated lipocalin-2, osteopontin and tissue inhibitor of metalloproteinases-1. Conclusion: This is the first study to demonstrate that AVP induces glomerular and tubular injury, as well as endothelial dysfunction in the pregnant Sprague Dawley rat model. These features are characteristic of renal injury observed in PE. Furthermore, AVP successfully elevated the urinary levels of most glomerular and tubular injury biomarkers as well as produced histological and ultrastructural renal abnormalities associated with human PE. Our data demonstrates the importance of kidney injury as early detection biomarkers for PE development. The findings support the use of the AVP rat model in future studies investigating the pathogenic processes involved in PE development.

Objective: To examine the placental immunoexpression of endoglin (Eng), in HIV-negative and HIV-positive normotensive (N and N+) and preeclamptic (P and P+) pregnancies at term, using immunohistochemistry and immunoelectron microscopy. Results: Strong Eng immunoreactivity was observed within endothelial cells, syncytio-and cyto-trophoblast cell populations. All extravillous trophoblast cells were immuno-positive for Eng. Subcellularly, gold particles were immunolocalised within the endoplasmic reticulum, and mitochondria. Immunoexpression of Eng differed signifi-cantly between exchange (p = 0.02) and conducting villi (p50.001). A higher Eng immunoexpression was observed in both villi types of the preeclamptic compared to normotensive groups. Irrespective of pregnancy type (normotensive versus PE), there was no significant effect of HIV status on Eng immunoexpression within the exchange and conducting villi. Conclusion: The immunostaining of Eng within the endothelial cells, syncytio-, cyto- and extravillous trophoblast cell populations of HIV-associated preeclamptic placentae is novel. Endoglin and its soluble component remains an area for dynamic placental exploration in preeclampsia development.

Faculty of Health Sciences

Browse

Filters

Settings

Sort By

Results per page

Search Results