Expression of ABC transporters during syncytialization in preeclampsia

Abstract

Preeclampsia complicates 2-8% of pregnancies and is associated with prematurity and intrauterine growth restriction. Cholesterol and sterol transport is a key function of the placenta and it is elicited through ATP binding cassette (ABC) transporters. ABCA1 expression changes during trophoblast cell fusion, a process required to form the placental syncytium that enables maternal-fetal nutrient transfer. ABCA1 expression is dysregulated in preeclamptic placentas. But whether ABC transporters expression during trophoblast fusion is disrupted in preeclampsia remains unknown. We investigated if cholesterol and sterol ABC transporters are altered in term and preterm preeclampsia placentas and during human cytotrophoblast syncytialization. Human placental biopsies were collected from healthy term (≥37 weeks; n = 11) and term preeclamptic (≥36 6/7 weeks; n = 8) and pre-term preeclamptic (28-35 weeks; n = 8) pregnancies. Both, protein and mRNA expression for ABCA1, ABCG1, ABCG5, and ABCG8 were evaluated. Primary cytotrophoblasts isolated from a subset of placentas were induced to syncytialize for 96 h and ABCA1, ABCG1 and ABCG8 mRNA expression evaluated at 0 h and 96 h. Protein and gene expression of ABC transporters were not altered in preeclamptic placentas. In the healthy Term group, ABCA1 expression was similar before and after syncytialization. After 96 h of syncytialization, mRNA expression of ABCA1 and ABCG1 increased significantly, while ABCG8 decreased significantly in term-preeclampsia, but not pre-term preeclampsia. While placental expression of ABCA1 and ABCG1 remained unaltered in term preeclampsia, the disruption in their dynamic expression pattern during cytotrophoblast syncytialization suggests that cholesterol transport may contribute to the pathophysiologic role of the placenta in preeclampsia.

Keywords: ABC transporters; Placenta; Syncytialization; Trophoblast.

Figure 1.

ABCA1 and ABCG5 protein expression (mean ± SEM) in human placental core biopsies in term (Term, open bars), term-preeclamptic (Term-PE, gray bars) and preterm-preeclamptic (PT-PE, closed bars) placentas (n = 24 (8/group)). Significance was set at P < 0.05.

Figure 2.

Relative mRNA expression (mean ± SEM) of ABCA1, ABCG1, ABCG8 in human placental core biopsies of term (Term, open bars, n = 11), term preeclampsia (Term-PE, gray bars, n = 8) and preterm preeclampsia (PT-PE, closed bars, n = 8) pregnancies. Significance was set at P < 0.05.

Figure 3.

Relative mRNA expression (mean ± SEM) of ABCA1 (top), ABCG1 (middle), and ABCG8 (bottom) in cytotrophoblasts before (0 h, open bars) and after 96 h of syncytialization with (closed bars) and without (gray bars) epidermal growth factor (EGF) derived from healthy term (Term, n = 4), term preeclampsia (Term-PE, n = 4) and preterm preeclampsia (PT-PE, n = 2) cytotrophoblasts. Asterisks denote differences between groups (* P < 0.05 and ** P < 0.01).