Estrogen enhances secretion of apolipoprotein B-100 containing lipoproteins by BeWo cells

Abstract

Although the early human embryo is capable of covering its cholesterol demand by endogenous synthesis, during later stages of development the fetus may become dependent on transplacental cholesterol transport. On one hand, this conclusion is based on the severe developmental abnormalities of embryos with mutations in the gene specifying the enzyme catalyzing the last step of cholesterol synthesis, 7-dehydrocholesterol reductase, causing Smith-Lemli-Opitz Syndrome. On the other hand, increased total maternal plasma cholesterol levels may reflect the requirement by the growing fetus and/or the placenta for cholesterol. Various molecules and complexes must cross the placental barrier consisting of trophoblasts and fetal endothelial cells to reach the fetal circulation. The de novo synthesis of apolipoprotein B (apoB)-containing lipoproteins coupled to secretion from trophoblasts towards the fetal side is one efficient pathway for cholesterol supply. ApoB and the microsomal triglyceride transfer protein (MTP) are essential components for the assembly of apoB-containing lipoproteins. The aim of this study was to evaluate functional properties of the human placental cell line BeWo as an in vitro model for placental synthesis of apoB-containing lipoproteins by focusing on components required for lipoprotein assembly and secretion. We demonstrate mRNA and protein production of apoB-100, MTP, and protein disulfide isomerase (PDI) in BeWo cells. In addition, metabolic radiolabeling and apoB-immunoprecipitation of cell extracts and media revealed that synthesis and secretion of apoB-containing lipoproteins are enhanced by estrogen. The expression of apoB-100, MTP, and PDI, and the estrogen-stimulated lipoprotein secretion by BeWo cells suggest that these cells are a useful system to study aspects of lipoprotein metabolism at the placental barrier.

Keywords: Apolipoprotein B; BeWo cells; Estrogen; Microsomal triglyceride transfer protein; Protein disulfide isomerase.