Abstract

Placental malaria is a common clinical complication during pregnancy and is associated with abortion, premature delivery, intrauterine growth retardation and low birth weight. The present study was designed to delineate the underlying mechanism of placental pathology during malarial infection with special reference to oxidative stress and apoptosis. Experimentally, pregnant BALB/c mice were infected with Plasmodium berghei infected red blood cells on gestation day 10. The presence of malarial infection in placenta was confirmed by histopathological studies. It was observation that infected placenta had plugged placental sinusoids with parasitized red blood cells and malarial pigments. Interestingly, we found significant increase in the level of malondialdehyde, the index of oxidative stress and decreased activity of catalase, the antioxidant in infected placenta. Furthermore, in infected placenta the oxidative stress mediated apoptosis was determined by DNA fragmentation assay, ethidium bromide/acridine orange staining and caspase activity. It was observed that oxidative stress begin after second day of malarial infection. Interestingly, it was observed that there was down regulation of anti-apoptotic protein Bcl-2 and up regulation of pro-apoptotic protein Bax in infected placenta, suggesting the involvement of mitochondrial pathway of apoptosis which was further confirmed by activation of caspase 9. However, no change in the expression of Fas gene and caspase 8 activity, indicated the absence of death receptor pathway. Thus, it can be concluded that the placental pathology during malarial infection is mediated by mitochondrial pathway of apoptosis occurring due to augmented lipid peroxidation which may in turn jeopardise the materno-fetal relationship.

Highlights

  • Malaria causes about 2.7 million deaths annually worldwide, most of which are in children and pregnant women [1]

  • It can be concluded that the placental pathology during malarial infection is mediated by mitochondrial pathway of apoptosis occurring due to augmented lipid peroxidation which may in turn jeopardise the materno-fetal relationship

  • The antigenic stimulation activates the immune system of the body thereby causing release of reactive oxygen species (ROS) [28,29]

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Summary

Introduction

Malaria causes about 2.7 million deaths annually worldwide, most of which are in children and pregnant women [1]. Despite all the efforts made to control malaria among pregnant women in endemic areas, malaria remains a significant cause of maternal and infant mortality and morbidity. In sub-Saharan Africa, the World hardest hit area by malaria, the infection is estimated to cause 4,00,000 cases of severe maternal anaemia and about 2,00,000 infant deaths [2,3,4]. Malarial infection caused by Plasmodium falciparum is more severe and frequent in pregnant women than in non-pregnant women. It is primigravidae who are more susceptible to the infection than multigravidae [5]. The non- immune, primigravidae are usually the most affected in areas of high transmission where 20–40% of all babies have a low birth weight whereas, in areas of low transmission primigravidae and multigravidae are affected [11,12]

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