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Abundance of megalin and Dab2 is reduced in syncytiotrophoblast during placental malaria, which may contribute to low birth weight.

Lybbert J, Gullingsrud J, Chesnokov O, Turyakira E, Dhorda M, Guerin PJ, Piola P, Muehlenbachs A, Oleinikov AV - Sci Rep (2016)

Bottom Line: The precise molecular details of placental changes leading to LBW are still poorly understood.We found that: (a) abundances of both megalin (p = 0.01) and Dab2 (p = 0.006) were significantly reduced in brush border of syncytiotrophoblast of infected placentas; (b) amounts of megalin and Dab2 were strongly correlated (Spearman's r = 0.53, p = 0.003); (c) abundances of megalin and Dab2 (p = 0.046) were reduced in infected placentas from women with LBW deliveries.This study provides first evidence that placental malaria infection is associated with reduced abundance of megalin transport/signaling system and indicate that these changes may contribute to the pathology of LBW.

View Article: PubMed Central - PubMed

Affiliation: Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA.

ABSTRACT
Placental malaria caused by Plasmodium falciparum contributes to ~200,000 child deaths annually, mainly due to low birth weight (LBW). Parasitized erythrocyte sequestration and consequent inflammation in the placenta are common attributes of placental malaria. The precise molecular details of placental changes leading to LBW are still poorly understood. We hypothesized that placental malaria may disturb maternofetal exchange of vitamins, lipids, and hormones mediated by the multi-ligand (n ~ 50) scavenging/signaling receptor megalin, which is abundantly expressed in placenta but was not previously analyzed in pregnancy outcomes. We studied abundance of megalin and its intracellular adaptor protein Dab2 by immunofluorescence microscopy in placental biopsies from Ugandan women with (n = 8) and without (n = 20) active placental malaria. We found that: (a) abundances of both megalin (p = 0.01) and Dab2 (p = 0.006) were significantly reduced in brush border of syncytiotrophoblast of infected placentas; (b) amounts of megalin and Dab2 were strongly correlated (Spearman's r = 0.53, p = 0.003); (c) abundances of megalin and Dab2 (p = 0.046) were reduced in infected placentas from women with LBW deliveries. This study provides first evidence that placental malaria infection is associated with reduced abundance of megalin transport/signaling system and indicate that these changes may contribute to the pathology of LBW.

No MeSH data available.


Related in: MedlinePlus

Correlation of megalin and Dab2 abundance in brush border area of syncytiotrophoblast.Correlation between amounts of Megalin and Dab2 was assessed using Spearman’s rank correlation coefficient (r). Megalin and Dab 2 abundance in all placentas (n = 28) was measured in arbitrary fluorescence units (AFU) using immunofluorescence assay as described in Methods. Six study participants (4 with PE and hemozoin, 1 with hemozoin only, and 1 without PE or hemozoin) did not have detectable megalin and Dab2. Line indicates linear regression, slope = 0.77 + 0.19, p = 0.0003. PE – parasitized erythrocytes in the placenta at the time of delivery. Hemozoin in the placenta at the time of delivery is indicative of past infection.
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f3: Correlation of megalin and Dab2 abundance in brush border area of syncytiotrophoblast.Correlation between amounts of Megalin and Dab2 was assessed using Spearman’s rank correlation coefficient (r). Megalin and Dab 2 abundance in all placentas (n = 28) was measured in arbitrary fluorescence units (AFU) using immunofluorescence assay as described in Methods. Six study participants (4 with PE and hemozoin, 1 with hemozoin only, and 1 without PE or hemozoin) did not have detectable megalin and Dab2. Line indicates linear regression, slope = 0.77 + 0.19, p = 0.0003. PE – parasitized erythrocytes in the placenta at the time of delivery. Hemozoin in the placenta at the time of delivery is indicative of past infection.

Mentions: Also, irrespective of PM status of samples, statistically significant positive correlation of megalin and Dab2 expression in the brush border region was observed (Fig. 3). A similar correlation was observed when the entire syncytiotrophoblast was analyzed (data not shown).


Abundance of megalin and Dab2 is reduced in syncytiotrophoblast during placental malaria, which may contribute to low birth weight.

Lybbert J, Gullingsrud J, Chesnokov O, Turyakira E, Dhorda M, Guerin PJ, Piola P, Muehlenbachs A, Oleinikov AV - Sci Rep (2016)

Correlation of megalin and Dab2 abundance in brush border area of syncytiotrophoblast.Correlation between amounts of Megalin and Dab2 was assessed using Spearman’s rank correlation coefficient (r). Megalin and Dab 2 abundance in all placentas (n = 28) was measured in arbitrary fluorescence units (AFU) using immunofluorescence assay as described in Methods. Six study participants (4 with PE and hemozoin, 1 with hemozoin only, and 1 without PE or hemozoin) did not have detectable megalin and Dab2. Line indicates linear regression, slope = 0.77 + 0.19, p = 0.0003. PE – parasitized erythrocytes in the placenta at the time of delivery. Hemozoin in the placenta at the time of delivery is indicative of past infection.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4829923&req=5

f3: Correlation of megalin and Dab2 abundance in brush border area of syncytiotrophoblast.Correlation between amounts of Megalin and Dab2 was assessed using Spearman’s rank correlation coefficient (r). Megalin and Dab 2 abundance in all placentas (n = 28) was measured in arbitrary fluorescence units (AFU) using immunofluorescence assay as described in Methods. Six study participants (4 with PE and hemozoin, 1 with hemozoin only, and 1 without PE or hemozoin) did not have detectable megalin and Dab2. Line indicates linear regression, slope = 0.77 + 0.19, p = 0.0003. PE – parasitized erythrocytes in the placenta at the time of delivery. Hemozoin in the placenta at the time of delivery is indicative of past infection.
Mentions: Also, irrespective of PM status of samples, statistically significant positive correlation of megalin and Dab2 expression in the brush border region was observed (Fig. 3). A similar correlation was observed when the entire syncytiotrophoblast was analyzed (data not shown).

Bottom Line: The precise molecular details of placental changes leading to LBW are still poorly understood.We found that: (a) abundances of both megalin (p = 0.01) and Dab2 (p = 0.006) were significantly reduced in brush border of syncytiotrophoblast of infected placentas; (b) amounts of megalin and Dab2 were strongly correlated (Spearman's r = 0.53, p = 0.003); (c) abundances of megalin and Dab2 (p = 0.046) were reduced in infected placentas from women with LBW deliveries.This study provides first evidence that placental malaria infection is associated with reduced abundance of megalin transport/signaling system and indicate that these changes may contribute to the pathology of LBW.

View Article: PubMed Central - PubMed

Affiliation: Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA.

ABSTRACT
Placental malaria caused by Plasmodium falciparum contributes to ~200,000 child deaths annually, mainly due to low birth weight (LBW). Parasitized erythrocyte sequestration and consequent inflammation in the placenta are common attributes of placental malaria. The precise molecular details of placental changes leading to LBW are still poorly understood. We hypothesized that placental malaria may disturb maternofetal exchange of vitamins, lipids, and hormones mediated by the multi-ligand (n ~ 50) scavenging/signaling receptor megalin, which is abundantly expressed in placenta but was not previously analyzed in pregnancy outcomes. We studied abundance of megalin and its intracellular adaptor protein Dab2 by immunofluorescence microscopy in placental biopsies from Ugandan women with (n = 8) and without (n = 20) active placental malaria. We found that: (a) abundances of both megalin (p = 0.01) and Dab2 (p = 0.006) were significantly reduced in brush border of syncytiotrophoblast of infected placentas; (b) amounts of megalin and Dab2 were strongly correlated (Spearman's r = 0.53, p = 0.003); (c) abundances of megalin and Dab2 (p = 0.046) were reduced in infected placentas from women with LBW deliveries. This study provides first evidence that placental malaria infection is associated with reduced abundance of megalin transport/signaling system and indicate that these changes may contribute to the pathology of LBW.

No MeSH data available.


Related in: MedlinePlus