Effect of Hydroxyprogesterone (17-OHPC) on Placenta in a Rat Model of Preeclampsia: Histological and Immunohistochemical Study

Abstract

Background: Preeclampsia (PE) is a leading cause of maternal and fetal morbidity and mortality. Patients with severe PE exhibit significantly lower serum progesterone concentrations. There is limited information about the use of progesterone to manage or treat PE.Aim of the work: To investigate the possible protective and/or therapeutic effects of 17-hydroxyprogesterone caproate (17-OHPC) therapy in a rat model of PE and the possibly involved mechanisms that monitored biochemically, histologically, and immunohistochemically.Methods: Twenty-four pregnant female albino rats were randomly divided into 4 groups (6 rats/each): The control group, preeclampsia group (PE-group), prophylactic group, and treated group. The mean arterial blood pressure (MAP) and 24-hour protein in urine were determined. Rats were sacrificed at day 22 of gestation and placentae were processed for paraffin.Results: The MAP and proteinuria in the PE-group were significantly higher compared to the control group. The prophylactic and treated groups showed significant decrease in MAP and proteinuria as compared to PE-group. In the treated group, they nearly returned to the normal levels. The histological examination of the PE-group showed dilated maternal blood sinuses, depositions of hemosiderin granules and numerous phagocytic trophoblastic cells containing cytoplasmic hemosiderin granules. Fetal blood vessels showed homogenous acidophilic material occluding their lumen, edema of the extra-embryonic fetal membranes and intra-villous tissue, and numerous nucleated RBCs. The prophylactic group showed some improvement while the treated group showed more or less normal maternal blood sinuses and interhemal membrane with few hemosiderin granules and few nucleated RBCs. There was a significant increase in caspase-3 expression and a significant decrease in the eNOS expression in PE-group compared to the control group. While the prophylactic and the treated groups had a significant decrease in caspase-3 expression and a significant increase in the eNOS expression compared to PE-group.Conclusion: The biochemical, morphological and morphometric findings suggested that the administration of 17-OHPC to preeclamptic rat decreased blood pressure, proteinuria, inflammation, apoptosis, and improved vascular eNOS expression in placenta. The 17-OHPC possessed curative effect on L-NAME induced PE changes in rat placenta which was more obvious than its protective effect.