Retinoic acid metabolizing enzyme CYP26A1 is implicated in rat embryo implantation
Retinoic acid metabolizing enzyme CYP26A1 is implicated in rat embryo implantation
复制标题
视黄酸代谢酶 CYP26A1 与大鼠胚胎着床有关
DOI：
10.1093/humrep/deq268
复制
发表时间：
2010-12-01
影响因子：
6.1
通讯作者：
Peng, Jing-Pian
中科院分区：
文献类型：
--
作者：
Xia, Hong-Fei;Ma, Jing-Jing;Peng, Jing-Pian
视黄酸代谢酶Cyp 26 a1在脊椎动物胚胎发育中起着关键作用。Cyp 26 a1以前的特点是作为一个差异表达的基因在围着床期大鼠子宫通过抑制消减杂交分析。本研究采用北方印迹、真实的时间PCR、原位杂交、Western印迹和免疫荧光染色等方法检测了Cyp 26 a1在大鼠早孕子宫、假孕子宫和人工蜕膜化子宫中的表达。采用原位末端标记法（TUNEL）和Hoechst染色观察Cyp 26 a1对大鼠子宫内膜间质细胞（ESCs）凋亡的影响。免疫印迹法检测凋亡相关蛋白的表达，Cyp 26 a1在胚胎和子宫中的表达在围着床期有明显差异，在着床期（妊娠第5.5-6.5天），Cyp 26 a1的mRNA和蛋白表达均显著增加（与第4-5天相比P < 0.01）。CYP 26 A1特异性定位于腺上皮、腔上皮和基底蜕膜。人工蜕膜化组子宫组织中CYP 26 A1蛋白水平显著高于对照组（P < 0.01）。Cyp 26 a1过度表达显著降低了ESCs对依托泊苷诱导的凋亡的敏感性，（P < 0.01）和Fas（P < 0.05）蛋白质与对照相比，而相反，FasL（P < 0.01）和增殖细胞核抗原Cyp 26 a1在胚胎着床和蜕膜化过程中的表达存在时空差异。Cyp 26 a1的过表达可能通过下调p53和FasL的表达而减弱子宫间质细胞的凋亡过程。
The retinoic acid metabolizing enzyme Cyp26a1 plays a pivotal role in vertebrate embryo development. Cyp26a1 was characterized previously as a differentially expressed gene in peri-implantation rat uteri via suppressive subtracted hybridization analysis. However, the role of Cyp26a1 in rat embryo implantation remained elusive.The expression of Cyp26a1 in the uteri of early pregnancy, pseudopregnancy and artificial decidualization was detected by northern blotting, real time-PCR, in situ hybridization, western blotting and immunofluorescent staining. The effect of Cyp26a1 on apoptosis of endometrial stromal cells (ESCs) isolated from rat uteri was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and Hoechst staining. Apoptosis-related proteins in ESCs were detected by western blotting.Cyp26a1 showed distinctive expression patterns in embryos and uteri during the peri-implantation period, with a remarkable increase (P < 0.01 versus Days 4-5) in mRNA and protein in the implantation phase (Days 5.5-6.5 of pregnancy). CYP26A1 was specifically localized in glandular epithelium, luminal epithelium and decidua basalis. The level of CYP26A1 protein was significantly increased in uteri of artificial decidualization (P < 0.01 versus control). Forced Cyp26a1 overexpression significantly reduced the sensitivity of ESCs to etoposide-induced apoptosis, with reductions in p53 (P < 0.01) and Fas (P < 0.05) proteins versus control, while in contrast, FasL (P < 0.01) and proliferating cell nuclear antigen (P < 0.05) proteins increased.Cyp26a1 is spatiotemporally expressed in the uterus during embryo implantation and decidualization. Overexpression of Cyp26a1 attenuates the process of uterine stromal cell apoptosis, probably via down-regulating the expression of p53 and FasL.