Postgraduate Department, Doctorate Program Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
Department of Obstetric and Gynecology, Division of Maternal Fetal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
PLoS One. 2018 Nov 8;13(11):e0206725. doi: 10.1371/journal.pone.0206725. eCollection 2018.
Preeclampsia and intra-uterine growth restriction (IUGR) are major health problems during pregnancy affecting both mother and child. Defective placental development and failure of trophoblast differentiation during pregnancy are important aspects in the pathogenesis of both syndromes. Recent studies have shown that autophagy is involved in the trophoblast survival capacity. As vitamin D has a central role in many cellular processes, we studied the relation of vitamin D and autophagy in those processes of preeclampsia and IUGR.
Serum and placental samples from four groups of cases; normal term, IUGR, early-onset and late-onset preeclampsia, were analyzed for 25(OH)D vitamin D, sFLT1, PGF, LGALS13 in serum and vitamin D receptor (VDR), MAP1LC3B and BECN1 in placental tissues.
There was a significant difference in the sFLT1/PGF ratio in preeclamptic cases compared to controls and IUGR. There was a significant difference between these groups in the MAP1LC3B/BECN1 ratio as marker of the trophoblast survival capacity with a significantly reduced ratio in villous trophoblast of early-onset preeclampsia. Maternal vitamin D deficiency was found in all pathological pregnancies combined with significantly reduced staining levels of placental VDR in IUGR. Finally, there was a strong and significant negative correlation between the survival capacity (MAP1LC3B/BECN1) and both maternal vitamin D and placental VDR in the preeclampsia groups.
Vitamin D and intracellular VDR are strongly related to the trophoblast survival capacity in preeclampsia.
子痫前期和宫内生长受限(IUGR)是妊娠期间的主要健康问题,会影响母婴双方。胎盘发育缺陷和滋养细胞分化失败是这两种综合征发病机制中的重要方面。最近的研究表明,自噬参与了滋养细胞的存活能力。由于维生素 D 在许多细胞过程中起着核心作用,我们研究了维生素 D 与自噬在子痫前期和 IUGR 这些过程中的关系。
分析了来自正常足月、IUGR、早发型和晚发型子痫前期四组病例的血清和胎盘样本,检测血清中 25(OH)D 维生素 D、sFLT1、PGF、LGALS13,以及胎盘组织中的维生素 D 受体(VDR)、MAP1LC3B 和 BECN1。
与对照组和 IUGR 相比,子痫前期患者的 sFLT1/PGF 比值存在显著差异。这些组之间的 MAP1LC3B/BECN1 比值存在显著差异,作为滋养细胞存活能力的标志物,早发型子痫前期的绒毛滋养细胞比值明显降低。所有病理性妊娠均存在母体维生素 D 缺乏,同时 IUGR 患者的胎盘 VDR 染色水平明显降低。最后,子痫前期组的生存能力(MAP1LC3B/BECN1)与母体维生素 D 和胎盘 VDR 呈强烈负相关。
维生素 D 和细胞内 VDR 与子痫前期的滋养细胞存活能力密切相关。