Winkler Brigitte Sophia, Pecks Ulrich, Najjari Laila, Kleine-Eggebrecht Nicola, Maass Nicolai, Mohaupt Markus, Escher Geneviève
Department of Obstetrics and Gynecology, University Hospital of RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany.
Department of Obstetrics and Gynecology, University Hospital of Schleswig-Holstein, Michaelisstraße 16, 24105, Kiel, Germany.
BMC Pregnancy Childbirth. 2017 Apr 4;17(1):106. doi: 10.1186/s12884-017-1287-7.
The oxysterol 27-hydroxycholesterol (27-OHC) plays an important role in the regulation of cholesterol homeostasis. Pregnancy pathologies like preeclampsia (PE), HELLP-syndrome (HELLP), intrauterine growth restriction (IUGR) and intrahepatic cholestasis in pregnancy (ICP) are linked to disturbances in lipid metabolism. In the present study, we hypothesized a specific gestational regulation of 27-OHC and compromised 27-OHC levels due to placental and hepatic diseases in pregnancy resulting in a dysregulation of lipid metabolism.
The 27-OHC was measured by gas-chromatography-mass spectrometry (GC-MS) and related to cholesterol concentrations. In the longitudinal cohort, a complete set of samples of healthy patients (n = 33) obtained at three different time points throughout gestation and once post-partum was analyzed. In the cross sectional cohort, patients with pregnancy pathologies (IUGR n = 14, PE n = 14, HELLP n = 7, ICP n = 7) were matched to a control group (CTRL) of equal gestational ages.
The 27-OHC levels already increased in the first trimester despite lower TC concentrations (p < 0.05). During the course of pregnancy, a subtle rise in 27-OHC concentrations results in an overall decrease of 27-OHC/TC ratio in between the first (p < 0.05) and second trimester. The ratio remains stable thereafter including the post-partum period. No significant differences have been observed in pregnancy pathologies as compared to the CTRL group.
In conclusion, 27-OHC may have a compensatory role in cholesterol metabolism early in pregnancy. The conserved 27-OHC/TC ratio in pregnancy pathologies suggest that neither the placenta nor the liver is majorly involved in the regulation of 27-OHC metabolism.
氧化型胆固醇27-羟基胆固醇(27-OHC)在胆固醇稳态调节中起重要作用。先兆子痫(PE)、溶血、肝酶升高和血小板减少综合征(HELLP)、胎儿生长受限(IUGR)以及妊娠期肝内胆汁淤积症(ICP)等妊娠病理情况与脂质代谢紊乱有关。在本研究中,我们假设27-OHC存在特定的孕期调节机制,且由于妊娠期间胎盘和肝脏疾病导致27-OHC水平受损,进而引起脂质代谢失调。
采用气相色谱-质谱联用(GC-MS)法测定27-OHC,并将其与胆固醇浓度相关联。在纵向队列研究中,分析了33名健康患者在整个孕期三个不同时间点及产后采集的完整样本集。在横断面队列研究中,将患有妊娠病理情况的患者(IUGR患者14例、PE患者14例、HELLP患者7例、ICP患者7例)与相同孕周的对照组(CTRL)进行匹配。
尽管孕早期总胆固醇(TC)浓度较低,但27-OHC水平已升高(p < 0.05)。在孕期过程中,27-OHC浓度的细微升高导致孕早期(p < 0.05)和孕中期之间27-OHC/TC比值总体下降。此后该比值保持稳定,包括产后阶段。与CTRL组相比,妊娠病理情况患者中未观察到显著差异。
总之,27-OHC可能在妊娠早期胆固醇代谢中起补偿作用。妊娠病理情况中27-OHC/TC比值保持不变,这表明胎盘和肝脏均未主要参与27-OHC代谢的调节。