Wang Li-Qin, Yan Xiao-Ting, Yan Chun-Fang, Zhang Xin-Wen, Hui Ling-Yun, Xue Mingzhan, Yu Xue-Wen
Department of Obstetrics and Gynecology in First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Nursing Department in Xi'an Medical College, Xi'an, China.
PLoS One. 2016 Dec 29;11(12):e0165589. doi: 10.1371/journal.pone.0165589. eCollection 2016.
Effects of vitamin D deficiency in pregnancy have been associated with some adverse pregnancy outcomes. The 25-hydroxyvitamin D3-1α-hydroxylase (CYP27B1) is integral to the vitamin D metabolic pathway. The enzyme catalyzes localized conversion of pro-hormone 25-hydroxyvitamin D3 to active 1,25-dihydroxyvitamin D3. Our aim was to investigate the expression of CYP27B1 at the fetal-maternal interface in the first trimester pregnancy and to determine whether CYP27B1 was associated with recurrent miscarriage (RM).
Expressions of CYP27B1 mRNA and protein in villi and decidua from 20 women undergoing primary miscarriage, 20 women with RM and 20 women with normal pregnancy were evaluated by western blot, and quantitative real-time PCR. The co-localization of CYP27B1 and certain cytokines including IL-10, IFN-γ, TNF-α, and IL-2 expression were examined using immunohistochemistry and confocal microscopy.
Women with RM had a significantly lower expression of CYP27B1 mRNA and protein in villous and decidual tissues compared with the normal pregnant women (P = 0.000 in villus, P = 0.002 in decidua for mRNA; P = 0.036 in villus, P = 0.007 in decidua for protein.). Compared with the normal pregnancy, immunostaining for CYP27B1 was significantly decreased in villous trophoblasts and decidual glandular epithelial cells in RM women. No significant differences in the localization of CYP27B1, IL-10, IFN-γ, TNF-α, and IL-2 expression were identified between the normal pregnant and RM women.
Women with RM have a lower level of CYP27B1 expression in chorionic villi and decidua compared with normal pregnant women, suggesting that reduced CYP27B1 expression may be associated with RM. The consistent localization of CYP27B1 and IL-10, IFN-γ, TNF-α, and IL-2 expression in villous and decidual tissues suggests the importance of the local production of 1,25(OH)2D3 at the fetal-maternal interface to regulate cytokine responses.
孕期维生素D缺乏的影响与一些不良妊娠结局有关。25-羟维生素D3-1α-羟化酶（CYP27B1）是维生素D代谢途径的关键组成部分。该酶催化激素原25-羟维生素D3局部转化为活性1,25-二羟维生素D3。我们的目的是研究孕早期胎儿-母体界面处CYP27B1的表达，并确定CYP27B1是否与复发性流产（RM）有关。
通过蛋白质免疫印迹法和定量实时聚合酶链反应，评估20例原发性流产妇女、20例RM妇女和20例正常妊娠妇女绒毛和蜕膜中CYP27B1 mRNA和蛋白的表达。采用免疫组织化学和共聚焦显微镜检查CYP27B1与某些细胞因子（包括IL-10、IFN-γ、TNF-α和IL-2）表达 的共定位情况。
与正常妊娠妇女相比，RM妇女绒毛和蜕膜组织中CYP27B1 mRNA和蛋白的表达显著降低（mRNA在绒毛中P = 0.000，在蜕膜中P = 0.002；蛋白在绒毛中P = 0.036，在蜕膜中P = 0.007）。与正常妊娠相比，RM妇女绒毛滋养层细胞和蜕膜腺上皮细胞中CYP27B1的免疫染色显著降低。正常妊娠妇女和RM妇女之间，CYP27B1、IL-10、IFN-γ、TNF-α和IL-2表达的定位没有显著差异。
与正常妊娠妇女相比，RM妇女绒毛膜绒毛和蜕膜中CYP27B1表达水平较低，提示CYP27B1表达降低可能与RM有关。CYP27B1与IL-10、IFN-γ、TNF-α和IL-2在绒毛和蜕膜组织中的表达一致，提示胎儿-母体界面处局部产生1,25(OH)2D3对调节细胞因子反应具有重要意义。
