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Due to the insufficient fetal cholesterol synthesis, maternal cholesterol transport through the placenta becomes an important source of fetal cholesterol pool, which is essential for fetal growth and development. This study aimed to investigate the effects of dexamethasone on fetal cholesterol levels, and explore its placental mechanism. Pregnant Wistar rats were injected subcutaneously with dexamethasone (0.8 mg/kg·d) from gestational day 9 to 20. Results showed that dexamethasone increased maternal serum total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) levels, as well as placental cholesterol synthesis and TC concentration, while reduced fetal birth weight, and serum TC, HDL-C and LDL-C levels. Meanwhile, the expression of placental cholesterol transporters, including low-density lipoprotein receptor (LDLR), scavenger receptor class B type I (SR-B1) and ATP-binding cassette transporter A1 and G1 (ABCA1 and ABCG1) were decreased by dexamethasone. Furthermore, the expression of glucocorticoid receptor (GR) and histone deacetylase 3 (HDAC3) were increased, while the H3K9ac and expression levels of liver X receptor α (LXRα) promoter were reduced. In human trophoblast cell line (BeWo), dexamethasone concentration-dependently decreased the expression levels of LDLR, SR-B1, ABCA1, ABCG1 as well as LXRα. Dexamethasone (2500 nM) induced GR translocation into nucleus and recruited HDAC3. Furthermore, LXRα agonist and GR inhibitor reversed respectively dexamethasone-induced the expression inhibitions of cholesterol transporter and LXRα, and HDAC3 siRNA reversed the H3K9ac level of LXRα promoter and its expression. Together, dexamethasone impaired placental cholesterol transport and eventually decreased fetal cholesterol levels, which is related to the down-regulation of LXRα mediated by GR/HDAC3/H3K9ac signaling.
This article was published in the following journal.
Name: Biochimica et biophysica acta. Molecular and cell biology of lipids
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A polypeptide hormone of approximately 25 kDa that is produced by the SYNCYTIOTROPHOBLASTS of the PLACENTA, also known as chorionic somatomammotropin. It has both GROWTH HORMONE and PROLACTIN activities on growth, lactation, and luteal steroid production. In women, placental lactogen secretion begins soon after implantation and increases to 1 g or more a day in late pregnancy. Placental lactogen is also an insulin antagonist.
Methods used for the assessment of placental function.
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