As células trofoblásticas de glicogênio murinas estão associadas à restrição do crescimento fetal em malária gestacional

Abstract

Gestational malaria, caused by Plasmodium infection during pregnancy, leads to severe complications such as anemia and low birth weight. The placenta plays a crucial role in fetal development by producing hormones, supplying nutrients and oxygen, and providing protection against infections. This study aimed to investigate the impact of Plasmodium berghei NK65GFP (PbNK65) infection on placental function and fetal growth in two mouse strains: C57BL/6 and BALB/c. To this end, pregnant female mice of both strains were infected with PbNK65 at gestational day 9.5 and analyzed at gestational day 16.5. Parasitemia was assessed over a time course. Fetal weight and placental weight were measured at day 16.5 of gestation (7 days post-infection), along with placental glycogen levels using PAS staining, and levels of glucagon, protocadherin 12 (Pcdh12), Ki-67, and matrix metalloproteinase-9 (MMP-9) in the uterus/placenta by immunohistochemistry. The results showed that PbNK65 infection led to significant reductions in placental glycogen content and fetal weight in both mouse strains. Uninfected C57BL/6 mice exhibited higher placental glycogen storage compared to uninfected BALB/c mice. However, infection caused a decrease in glycogen storage in both strains, with a greater impact observed in BALB/c mice. Glucagon and Pcdh12 expression were increased in the placental tissues of infected BALB/c animals, while remaining unchanged or decreased, respectively, in C57BL/6 mice, suggesting a potential adaptive response to infection. The infection also increased MMP-9 levels in the placentas of C57BL/6 animals, and these levels were higher in C57BL/6 mice compared to BALB/c mice. In conclusion, both mouse strains showed reduced glycogen storage and fetal weight under PbNK65 infection. However, BALB/c fetuses exhibited less weight loss compared to the C57BL/6 strain, which was associated with higher levels of glucagon and Pcdh12 in the placental tissues of BALB/c mice. These findings suggest that glycogen storage and glycogen trophoblast cells play a role in maintaining fetal weight during gestational malaria, and that increased MMP-9 abundance in the placentas of C57BL/6 mice indicates an inflammatory response that may negatively impact gestational health. Keywords: Gestational malaria; Plasmodium berghei NK65; glycogen trophoblast cells; glycogen storage; fetal weight.