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

Mila W Reginatto; Klaus Novaes Fontes; Victoria R S Monteiro; Natalia L Silva; Cherley Borba Vieira Andrade; Hanailly Ribeiro Gomes; Guinever E Imperio; Flavia Fonseca Bloise; George Eduardo Gabriel Kluck; Georgia Correa Atella; Stephen G Matthews; Enrrico Bloise; Tania M Ortiga-Carvalho

doi:10.3389/fmicb.2021.706499

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

Front Microbiol. 2021 Jul 30:12:706499. doi: 10.3389/fmicb.2021.706499. eCollection 2021.

Authors

Mila W Reginatto¹, Klaus Novaes Fontes¹, Victoria R S Monteiro¹, Natalia L Silva¹, Cherley Borba Vieira Andrade¹, Hanailly Ribeiro Gomes¹, Guinever E Imperio^{1

2

3}, Flavia Fonseca Bloise¹, George Eduardo Gabriel Kluck⁴, Georgia Correa Atella⁴, Stephen G Matthews^{2

3

5

6}, Enrrico Bloise⁷, Tania M Ortiga-Carvalho¹

Affiliations

¹ Laboratory of Translational Endocrinology, Institute of Biophysics Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
² Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
³ Lunenfeld-Tanenbaum Research Institute of Medical, Sinai Health System, Toronto, ON, Canada.
⁴ Laboratory of Lipids and Lipoproteins Biochemistry, Institute of Medical Biochemistry Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
⁵ Department of Obstetrics and Gynecology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
⁶ Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
⁷ Department of Morphology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

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.

Keywords: ABC sub-family G member 1; ATP binding cassette transporters; FAtty acid translocase; P-glycoprotein; breast cancer resistance protein; cholesterol; fatty acid binding protein associated with plasma membrane; lipopolysaccharide.