Department of Paediatrics and Adolescent Medicine, University of Erlangen-Nuremberg, Germany.
Eur J Obstet Gynecol Reprod Biol. 2011 May;156(1):50-5. doi: 10.1016/j.ejogrb.2011.01.008. Epub 2011 Feb 2.
Fetal glucocorticoid excess is thought to play an important role in early-life programming, promoting growth restriction and contributing to adult metabolic, cardiovascular and neuroendocrine disease. We hypothesized that dexamethasone incubation of primary trophoblastic cells from human healthy placentas at term might induce altered gene and protein expression of several endocrine placental regulators.
Primary villous trophoblastic cells were incubated with 10 μM dexamethasone for 6, 12, 24, 48 and 72 h. Non-incubated trophoblastic cells served as vehicle control. Gene expression of leptin, 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) and insulin-like growth factor-binding protein-1 (IGFBP-1) was measured. Moreover, leptin, β-human chorionic gonadotropine (β-hCG) and lactate dehydrogenase (LDH) release into the culture medium was determined.
Leptin gene expression was significantly increased in dexamethasone-incubated trophoblastic cells after 24, 48 and 72 h. There was a significant increase in leptin concentration in the medium of the cell culture after 48 h. Gene expression of 11β-HSD2 was significantly higher in dexamethasone-stimulated trophoblastic cells compared to vehicle controls after 72 h. The expression rate of IGFBP-1 mRNA was basal throughout the incubation period. The concentration of β-HCG in the supernatant increased significantly after 72 h of dexamethasone incubation, while LDH concentrations remained stable.
Our findings suggest that dexamethasone incubation stimulates leptin and 11β-HSD2 gene expression in primary villous trophoblastic cells of healthy human placentas, while enhancing cytotrophoblast differentiation.
胎儿糖皮质激素过多被认为在生命早期编程中发挥重要作用，促进生长受限，并导致成年期代谢、心血管和神经内分泌疾病。我们假设，在足月时用地塞米松孵育人健康胎盘的初级滋养细胞可能会诱导几种内分泌胎盘调节剂的基因和蛋白表达发生改变。
将初级绒毛滋养细胞用 10 μM 地塞米松孵育 6、12、24、48 和 72 小时。未孵育的滋养细胞作为载体对照。测量瘦素、11β-羟类固醇脱氢酶 2（11β-HSD2）和胰岛素样生长因子结合蛋白-1（IGFBP-1）的基因表达。此外，还测定了培养基中瘦素、β-人绒毛膜促性腺激素（β-hCG）和乳酸脱氢酶（LDH）的释放。
地塞米松孵育的滋养细胞中瘦素基因表达在 24、48 和 72 小时后显著增加。48 小时后，细胞培养物培养基中的瘦素浓度显著增加。与载体对照相比，地塞米松刺激的滋养细胞中 11β-HSD2 的基因表达在 72 小时后显著增加。IGFBP-1mRNA 的表达率在整个孵育期间保持基础水平。地塞米松孵育 72 小时后，上清液中β-HCG 的浓度显著增加，而 LDH 浓度保持稳定。
我们的研究结果表明，地塞米松孵育刺激健康人胎盘初级绒毛滋养细胞中瘦素和 11β-HSD2 的基因表达，同时增强滋养细胞的分化。
