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Placental ABCA1 and ABCG1 expression in gestational disease: Pre-eclampsia affects ABCA1 levels in
1Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, Bern, Switzerland; Department of Obstetrics and Gynecology, University Hospital, University of Bern, Bern, Switzerland.
Insights
Placental ATP-binding cassette transporter ABCA1 is down-regulated in pre-eclampsia, impairing lipid exchange and increasing placental lipids. ABCG1 levels remained stable in gestational diseases.
Area of Science:
- Reproductive biology
- Molecular genetics
- Obstetrics
Background:
- Transplacental lipid exchange via ATP-binding cassette transporters ABCA1 and ABCG1 is vital for fetal development.
- Limited data exist on the role of these transporters in gestational diseases.
Purpose of the Study:
- To investigate the expression and function of ABCA1 and ABCG1 in placentas from pregnancies complicated by common gestational diseases.
- To determine if ABCA1 or ABCG1 are implicated in the pathophysiology of pre-eclampsia, HELLP, IUGR, intrahepatic cholestasis of pregnancy, and gestational diabetes.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) and immunohistochemistry were used to assess ABCA1 and ABCG1 mRNA and protein levels in 72 placenta samples.
- ABCA1 protein expression was further analyzed in placental membrane vesicles using immunoblot.
- Placental cholesterol and phospholipid content were quantified.
Main Results:
- ABCA1 mRNA levels showed significant differences between preterm and term control placentas.
- A significant down-regulation of ABCA1 mRNA and protein was observed in pre-eclampsia (PE) and PE with intrauterine growth restriction (IUGR).
- Placental phospholipid content increased in PE, correlating with reduced ABCA1 expression, while ABCG1 levels remained unchanged across conditions.
Conclusions:
- Placental ABCA1 expression is specifically downregulated in pre-eclampsia, affecting feto-maternal lipid exchange.
- Increased placental lipid concentrations in PE suggest impaired ABCA1 transport function.
- ABCG1 expression is not significantly altered in the studied gestational diseases.
Introduction:
Transplacental feto-maternal lipid exchange through the ATP-binding cassette transporters ABCA1 and ABCG1 is important for normal fetal development. However, only scarce and conflicting data exist on the involvement of these transporters in gestational disease.
Methods:
Placenta samples (n = 72) derived from common gestational diseases, including pre-eclampsia (PE), HELLP, intrauterine growth restriction (IUGR), intrahepatic cholestasis of pregnancy and gestational diabetes, were assessed for their ABCA1 and ABCG1 expression levels and compared to age-matched control placentas with qRT-PCR and immunohistochemistry. ABCA1 expression was additionally investigated with immunoblot in placental membrane vesicles. Furthermore, placental cholesterol and phospholipid contents were assessed.
Results:
ABCA1 mRNA levels differed significantly between preterm and term control placentas (p = 0.0013). They were down-regulated in isolated PE and PE with IUGR (p = 0.0006 and p = 0.0012, respectively), but unchanged in isolated IUGR, isolated HELLP and other gestational diseases compared to gestational age-matched controls. Correspondingly, in PE, ABCA1 protein expression was significantly reduced in the apical membrane of the villous syncytiotrophoblast (p = 0.011) and in villous fetal endothelial cells (p = 0.036). Furthermore, in PE there was a significant increase in the placental content of total and individual classes of phospholipids which were partially correlated with diminished ABCA1 expression. Conversely, ABCG1 mRNA and protein levels were stable in the investigated conditions.
Conclusions:
In gestational disease, there is a specific down-regulation of placental ABCA1 expression at sites of feto-maternal lipid exchange in PE. At a functional level, the increase in placental lipid concentrations provides indirect evidence of an impaired transport capacity of ABCA1 in this disease.
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