FRI492 Malaria In Pregnancy And Lipopolyssacharide Lead To Sex-specific Changes In The Expression Of Genes Involved In The Placental Metabolism Of Thyroid Hormones

Abstract

Abstract Disclosure: K.N. Fontes: None. V.S. Monteiro: None. C.B. Andrade: None. A.C. Valim: None. V.M. Nascimento: None. D.E. Teixeira: None. A.A. Pinheiro: None. E. Bloise: None. T.M. Ortiga-Carvalho: None. Infection during gestation promotes marked changes in placental physiology, leading to intrauterine growth restriction (IUGR), preterm labor (PTL) and neurodevelopmental disorders. Infection in pregnant women or mice may impact thyroid hormones’ (TH) metabolism and the importance of TH for the development of the placenta and conceptus is widely described in the literature. Our main aim was to evaluate changes in the expression of specific genes involved in placental TH metabolism triggered by malaria in pregnancy (MiP) or bacterial lipopolyssacharide (LPS), in the male and female placenta. Female C57BL/6 mice (8-10 weeks of age) were mated. In the MiP model, dams were infected ip with Plasmodium Berghei ANKA-infected erythrocytes (PBA; 5x105 infected-erythrocytes, n=10) or injected with PBS (contro; n=10) at gestational day (GD)13.5 and sacrificed at GD18.5. In the LPS model, dams were injected ip with LPS (150 µg/kg, n=10) or PBS (control; n=10) at GD17.5 and sacrificed at GD18.5. Maternal blood was collected to evaluate PBA parasitemia. Placental disks were collected from dams delivering at term (GD18.5), and qPCR was performed to evaluate the mRNA expression of genes involved in placental TH metabolism. MiP was confirmed by analysis of parasitemia (15.9%), and resulted in increased maternal spleen weight (P<0.05). As expected, MiP induced PTL (at GD17.5) in 23.1% of dams. Fetal weight and fetal/placental weight ratio were reduced in MiP (at term), compared to control (P<0.05). In the LPS model, 33.3% of dams went into PTL (at GD17.5) and fetal weight was reduced in LPS group (at term), compared to control (P<0.05). In both models, mRNA of the Cxcl1 chemokine (P<0.05) was increased in the male and female placenta at term (P<0.05). Male MiP placentas exhibited a reduction in Slc7a8 (P<0.05) and Dio2 (P<0.05) mRNA expression, whereas female MiP placentas exhibited a reduction in Slc7a8 (P<0.05) and an increase in Slco1c1 and Dio1 (P<0.05) at term. LPS increased Dio1 (P<0.05) mRNA in the male term placenta, and increased Ccl2 (P<0.05) mRNA in the term female placenta. In the present study, MiP was associated with sex-specific changes in the placental expression of TH transporters and deiodinases, while LPS injection promoted a limited effect on placental TH metabolism, but increased the expression of placental inflammatory markers at term. We speculate that these changes may result in reduced TH transport from mother to fetus, leading to IUGR among surviving fetuses, especially in pregnancies threatened by MiP. Presentation: Friday, June 16, 2023