Effect of Sublethal Prenatal Endotoxaemia on Murine Placental Transport Systems and Lipid Homeostasis

Abstract

Infection alters the expression of transporters that mediate the placental exchange of xenobiotics, lipids and cytokines. We hypothesized that lipopolysaccharide (LPS) modifies the expression of placental transport systems and lipid homeostasis. LPS (150 μg/kg; i.p.) treatments were administered for 4 h or 24 h, animals were euthanized at gestational days (GD) 15.5 or 18.5, and maternal blood, fetuses and placentae were collected. Increased rates of fetal demise were observed at GD15.5 following LPS treatment, whereas at GD18.5, high rates of early labour occurred and were associated with distinct proinflammatory responses. Lipopolysaccharide did not alter ATP-binding cassette (ABC) transporter mRNA expression but decreased fatty acid binding protein associated with plasma membrane (Fabppm) at GD15.5 (LPS-4 h) and increased fatty acid translocase (Fat/Cd36) mRNA at GD18.5 (LPS-4 h). At the protein level, breast cancer-related protein (Bcrp) and ABC sub-family G member 1 (Abcg1) levels were decreased in the placental labyrinth zone (Lz) at GD15.5, whereas P-glycoprotein (P-gp) and Bcrp Lz-immunostaining was decreased at GD18.5. In the placental junctional zone (Jz), P-gp, Bcrp and Abcg1 levels were higher at GD18.5. Specific maternal plasma and placental changes in triacylglycerol, free fatty acid, cholesterol, cholesterol ester and monoacylglycerol levels were detected in a gestational age-dependent manner. In conclusion, LPS-increased risk of fetal death and early labour were associated with altered placental ABC and lipid transporter expression and deranged maternal plasma and placental lipid homeostasis. These changes may potentially modify fetal xenobiotic exposure and placental lipid exchange in cases of bacterial infection.

Mid-pregnancy poly(I:C) viral mimic disrupts placental ABC transporter expression and leads to long-term offspring motor and cognitive dysfunction

“…In the present study, Poly(I:C) did not modify Abca1 gene expression. This is similar to what we observed following maternal lipopolysaccharide (LPS) exposure 11 , but contrary to what we found in a gestational malaria model. 13 At the protein level, poly(I:C) decreased Abca1 staining in the Lz but increased staining in Jz, similar to what was found in malaria and ZIKV models.…”

“…However, in recent studies we demonstrated speci c and independent responses of labyrinth and junctional zones. [11][12][13] In the present study, we showed that poly(I:C) affects both the labyrinth and junctional zones, causing region speci c placental remodeling. Further, ABC transporters levels in these two placental regions were affected in an opposite way following poly(I:C) treatment, reinforcing the importance of investigating these two zones separately.…”

“…12,13 Poly(I:C) decreased Abcg1 gene expression in the Jz of the placenta. However, malaria infection 13 and LPS challenge 11 did not affect Abcg1 mRNA levels in this region of the mouse placenta. Similar to what happen in LPS infection 11 , poly(I:C) impact Abcg1 protein decreasing its expression in Lz and increasing it in the Jz.…”

“…However, malaria infection 13 and LPS challenge 11 did not affect Abcg1 mRNA levels in this region of the mouse placenta. Similar to what happen in LPS infection 11 , poly(I:C) impact Abcg1 protein decreasing its expression in Lz and increasing it in the Jz. Given that cholesterol is essential for several development processes 43,44 , the present data would suggest that mid-pregnancy poly(I:C) treatment would impair fetal development.…”

“…41 Previous studies have shown poly(I:C) treatment on GD13.5 in the pregnant rat to decrease placental weight, area and thickness. 42 Of all the studies involving gestational infections by different pathogens and viral mimics from our group [11][12][13] , poly(I:C) was not able to affect fetal weight and the fetal weight/placental weight ratio.…”