Placental apoptotic markers are associated with placental morphometry.

INTRODUCTION: Preeclampsia is a hypertensive disorder affecting both mother and the fetus and is a major cause of maternal and neonatal morbidity and mortality. Abnormal placentation is a common feature in preeclampsia that contributes to placental dysfunction. It is likely that increased homocysteine and oxidative stress influence apoptosis in preeclampsia. Increased placental apoptosis may aggravate the symptoms of preeclampsia through disruption of the placental structure. The current study aims to examine the association between various placental apoptotic markers with placental dimensions and maternal and neonatal characteristics in women with preeclampsia. METHODS: A total of 80 pregnant women [preeclampsia (n = 40); normotensive control (n = 40)] were included in the study. Placental characteristics such as its major axis, minor axis, breadth, thickness (at centre, cord insertion and periphery) and trimmed placental weight were recorded.Placental protein levels of caspase-3, caspase-8, BAX and Bcl-2 were estimated by ELISA and gene expression were examined by real time quantitative PCR. RESULT: Protein levels of proapoptotic markers such as caspase-8 and 3 were higher (p < 0.01) in the preeclampsia group compared to control whereas, the level of antiapoptotic marker Bcl-2 (p < 0.05) was lower in the preeclampsia group. Caspase-3 and Bcl-2 protein levels were negatively associated with thickness of placenta at cord insertion (p < 0.01). Protein levels of caspase-8 and caspase-3 were positively associated with placental MDA levels (p < 0.01). Caspase-8 was negatively associated with baby length (p = 0.055). DISCUSSION: This study demonstrates the association of various apoptotic markers with oxidative stress and placental dimensions.

Effect of maternal omega-3 fatty acids and vitamin E supplementation on placental apoptotic markers in rat model of early and late onset preeclampsia.

AIM: Disturbed placentation results in pregnancy complications like preeclampsia. Placental development is influenced by apoptosis during trophoblast differentiation and proliferation. Increased oxidative stress upregulates placental apoptosis. We have earlier reported increased oxidative stress, lower omega-3 fatty acids and vitamin E levels in women with preeclampsia. Current study examines effect of maternal omega-3 fatty acids and vitamin E supplementation on apoptotic markers across gestation in a rat model of preeclampsia. MAIN METHODS: Pregnant Wistar rats were randomly assigned to control; early onset preeclampsia (EOP); late onset preeclampsia (LOP); early onset preeclampsia + omega-3 fatty acid + vitamin E supplementation (EOP + O + E) and late onset preeclampsia + omega-3 fatty acid + vitamin E supplementation (LOP + O + E) groups. Animals (Control, EOP, EOP + O + E) were sacrificed at d14 and d20 of gestation while animals (LOP, LOP + O + E) were sacrificed at d20 to collect blood and placentae. Protein and mRNA levels of apoptotic markers were analyzed by ELISA and RT-PCR respectively. KEY FINDINGS: Protein levels of proapoptotic markers like Bcl-2 associated X-protein (BAX) (p < 0.05), caspase-8 and 3 (p < 0.01 for both) and malondialdehyde (p < 0.01) were higher only in the EOP group as compared to control. However, the antiapoptotic marker, B cell lymphoma 2 (Bcl-2) protein levels were lower in both the subtypes of preeclampsia (p < 0.01 for both). SIGNIFICANCE: Our findings suggest that supplementation was beneficial in reducing the caspase-8 and 3 in early onset preeclampsia but did not normalize BAX and Bcl-2 levels. This has implications for reducing placental apoptosis in preeclampsia.

Maternal omega-3 fatty acids and vitamin E improve placental angiogenesis in late-onset but not early-onset preeclampsia.

Abnormal placental vasculature is associated with preeclampsia. Preeclampsia is of two types, i.e., early- and late-onset preeclampsia (LOP), both having different etiologies. We have earlier demonstrated low levels of omega-3 fatty acids and vitamin E in women with preeclampsia. The current study examines the effect of maternal omega-3 fatty acids and vitamin E supplementation on angiogenic factors in a rat model of preeclampsia. Pregnant rats were divided into a total of five groups control, early-onset preeclampsia (EOP); LOP; EOP supplemented with omega-3 fatty acid and vitamin E and LOP supplemented with omega-3 fatty acid and vitamin E. Preeclampsia was induced by administering L-nitroarginine methylester (L-NAME) at the dose of 50 mg/kg body weight/day. The vascular endothelial growth factor gene expression and protein levels were lower (p < 0.01 for both) in animals from both EOP as well as LOP groups (p < 0.01). In the EOP group, the protein levels of VEGF receptor-1 were also lower (p < 0.01). Supplementation of omega-3 fatty acids and vitamin E to LOP improved the levels of VEGF and VEGF receptor-1 only in the LOP but not in the EOP group. In the EOP group, the gene expression of hypoxia inducible factor 1 alpha (HIF-1α) in the placenta was higher (p < 0.05) and supplementation normalized these levels. Our findings indicate that maternal supplementation of omega-3 fatty acids and vitamin E has differential effect on preeclampsia subtypes.