pre-eclampsia; placenta; transport ; pregnancy ; aldosterone; cholesterol; steroidogenesis; human placenta perfusion
Fuenzalida Bárbara, Cantin Claudette, Kallol Sampada, Carvajal Lorena, Pastén Valentina, Contreras-Duarte Susana, Albrecht Christiane, Gutierrez Jaime, Leiva Andrea (2020), Cholesterol uptake and efflux are impaired in human trophoblast cells from pregnancies with maternal supraphysiological hypercholesterolemia, in Scientific Reports
, 10(1), 1-16.
Kallol Sampada, Albrecht Christiane (2020), Materno-fetal cholesterol transport during pregnancy, in Biochemical Society Transactions
Albrecht C., Chamley L., Charnock-Jones D.S., Collins S., Fujiwara H., Golos T., Grayo S., Hannan N., Harris L., Ichizuka K., Illsley N.P., Iwashita M., Kallol S., Al-Khan A., Lash G., Nagamatsu T., Nakashima A., Niimi K., Nomoto M., Redman C., Saito S., Tanimura K., Tomi M., Usui H., Vatish M., Wolfe B., Yamamoto E., O'Tierney-Ginn P. (2019), IFPA meeting 2018 workshop report II: Abnormally invasive placenta; inflammation and infection; preeclampsia; gestational trophoblastic disease and drug delivery
, 84, 9-13, Elsevier, Amsterdam 84, 9-13.
Melhem H., Kallol S., Huang X., Lüthi M., Ontsouka C.E., Keogh A., Stroka D., Thormann W., Schneider H., Albrecht C. (2019), Placental secretion of apolipoprotein A1 and E: the anti-atherogenic impact of the placenta, in Scientific Reports
, 9(1), 1-12.
Schroeder Mariana, Jakovcevski Mira, Polacheck Tamar, Drori Yonat, Luoni Alessia, Röh Simone, Zaugg Jonas, Ben-Dor Shifra, Albrecht Christiane, Chen Alon (2018), Placental miR-340 mediates vulnerability to activity based anorexia in mice, in Nature Communications
, 9(1), 1596-1596.
Huang Xiao, Anderle Pascale, Hostettler Lu, Baumann Marc U., Surbek Daniel V., Ontsouka Edgar C., Albrecht Christiane (2018), Identification of placental nutrient transporters associated with intrauterine growth restriction and pre-eclampsia, in BMC Genomics
, 19(1), 173-173.
Kallol S., Moser-Haessig R., Ontsouka C.E., Albrecht C. (2018), Comparative expression patterns of selected membrane transporters in differentiated BeWo and human primary trophoblast cells, in Placenta
, 72-73, 48-52, Elsevier, Amsterdam 72-73, 48-52.
Albrecht Christiane, Baker Julie C., Blundell Cassidy, Chavez Shawn L., Carbone Lucia, Chamley Larry, Hannibal Roberta L., Illsley Nick, Kurre Peter, Laurent Louise C., McKenzie Charles, Morales-Prieto Diana, Pantham Priyadarshini, Paquette Alison, Powell Katie, Price Nathan, Rao Balaji M., Sadovsky Yoel, Salomon Carlos, Tuteja Geetu, Wilson Samantha, O'Tierney-Ginn P.F. (2017), IFPA meeting 2016 workshop report I: Genomic communication, bioinformatics, trophoblast biology and transport systems, in Placenta
, 60, S5-S9.
Sampada Kallol (2017), Effect of placental cell differentiation on materno-fetal nutrient transport, in IFPA 2017
, Elsevier, UK.
Albrecht C., Caniggia I., Clifton V., Göhner C., Harris L., Hemmings D., Jawerbaum A., Johnstone E., Jones H., Keelan J., Lewis R., Mitchell M., Murthi P., Powell T., Saffery R., Smith R., Vaillancourt C., Wadsack C., Salomon C. (2016), IFPA meeting 2015 workshop report III: nanomedicine applications and exosome biology, xenobiotics and endocrine disruptors and pregnancy, and lipid, in Placenta
, 48, S12-S16.
Sampada Kallol (2016), Differential expression of selected placental membrane transporters during syncytium formation in vitro, in IFPA 2016
, Elsevier, UK.
Huang Xiao, Lüthi Michael, Ontsouka Edgar C, Kallol Sampada, Baumann Marc U, Surbek Daniel V, Albrecht Christiane (2016), Establishment of a confluent monolayer model with human primary trophoblast cells: novel insights into placental glucose transport., in Molecular human reproduction
, 22(6), 442-56.
Eisele Nicole, Albrecht Christiane, Mistry Hiten D, Dick Bernhard, Baumann Marc, Surbek Daniel, Currie Gemma, Delles Christian, Mohaupt Markus G, Escher Geneviève, Gennari-Moser Carine (2016), Placental expression of the angiogenic placental growth factor is stimulated by both aldosterone and simulated starvation., in Placenta
, 40, 18-24.
Arjun Jain, Christiane Albrecht (2015), Importance of Cholesterol and Cholesterol Transporters in the Placental Trophoblast during Pregnancy., in Asim K. Duttaroy Sanjay Basak (ed.), CRC Press, USA, 129-144.
Xiao Huang (2015), Identification of important placental nutrient transporters in intrauterine growth restriction and preeclampsia using various strategies, in IFPA 2015
, Elsevier, UK.
Xiao Huang (2015), Impaired placental thiamine transport in human pregnancy diseases, in IFPA 2015
, Elsevier, UK.
Jain Arjun, Schneider Henning, Aliyev Eldar, Soydemir Fatimah, Baumann Marc, Surbek Daniel, Hediger Matthias, Brownbill Paul, Albrecht Christiane (2014), Hypoxic treatment of human dual placental perfusion induces a preeclampsia-like inflammatory response., in Laboratory investigation; a journal of technical methods and pathology
, 94(8), 873-80.
The ATP-binding cassette transporter A1 (ABCA1) mediates the transport of cholesterol, phospholipids and other lipophilic compounds across cellular membranes. Hereby it is implicated in the physiology of cellular cholesterol homeostasis and reverse cholesterol transport as well as in hereditary lipid disorders and atherosclerosis. Lately, evidence evolved on the role of ABCA1 in normal and pathological pregnancies at the placenta level. Studies in ABCA1 null mice revealed catastrophic effects of ABCA1 deficiency in the placenta including intrauterine growth restriction and increased rates of neonatal death. Moreover, we recently have demonstrated differential ABCA1 mRNA and protein expression in placentas obtained from patients with pre-eclampsia, a clinically severe gestational disease with lifelong consequences for both mother and child, where ABCA1 was specifically downregulated in syncytiotrophoblasts and fetal endothelial cells, i.e. particularly at the sites of materno-fetal cholesterol exchange. However, the mode of action as well as the molecular mechanisms underlying and controlling ABCA1 function in the human placenta in health and disease are only poorly understood. Novel data from our group suggested that manipulating ABCA1 function in placental primary cells has severe effects on the placental production of progesterone, a steroid hormone essential for the maintenance of pregnancy. Moreover, preliminary studies from our laboratory indicated that aldosterone, a hormone recently acknowledged as of major importance for the uteroplacental unit, showed a novel formerly unrecognized action on ABCA1. Aldosterone downregulated ABCA1 function in the frequently used RAW 264.7 macrophage model but not in placental syncytiotrohoblasts despite functional mineralocorticoid receptors being expressed in both cell types. This suggests a differential regulation of ABCA1 protecting the placenta from this adverse effect of aldosterone and provides a potential key to understand aldosterone-induced vasculopathy and accelerated atherosclerosis.To elucidate the relevance of ABCA1 in physiology and pathophysiology of the human placenta and to identify underlying control mechanisms of ABCA1 action in this organ, our research team will perform a rigorous examination of the regulatory factors and signaling pathways, and to explore the cause and relevance of reduced ABCA1 expression in pre-eclampsia. Our central hypotheses are that I) ABCA1 function in the placenta is maintained despite high aldosterone levels indicating differential regulation to preserve transplacental cholesterol transport and that II) ABCA1 activity during pregnancy has to be tightly controlled to maintain cholesterol-dependent steroid hormone synthesis within the placenta. To test these assumptions we will a) investigate the role and mode of action of aldosterone in the regulation of ABCA1 expression and function in a variety of relevant placenta-derived primary cells, macrophages and control cells, b) determine the impact of ABCA1 in the maintenance of steroid hormone synthesis/metabolism in the placenta, c) investigate the control mechanisms of ABCA1 expression and function in healthy placentas, and its dysregulation in pre-eclampsia. In all of the above mentioned investigations we will assure to delineate the role of ABCA1 from other lipid transporters and sterol responsive genes.The results of these studies will contribute to a better understanding of the mode(s) of action of ABCA1 in the human placenta and the reasons and pathophysiological consequences associated with dysregulated ABCA1 function. Our investigations will reveal whether and by which mechanism ABCA1 contributes to normal placental development, and will provide novel insights into the regulatory mechanisms which control ABCA1 action in the healthy and compromised placenta. The identification of ABCA1, or other candidate genes investigated in our studies, as potential key players in pre-eclampsia might generate novel options for diagnosis or therapeutic intervention in this severe and clinically relevant disease. Furthermore, this research is likely to explain some features of vasculopathy and accelerated atherosclerosis in high aldosterone states in non-pregnant individuals and to identify candidate protective pathways.