Retinoic Acid-Metabolizing Enzyme Cytochrome P450 26a1 (Cyp26a1) Is Essential for Implantation: Functional Study of Its Role in Early Pregnancy
Retinoic Acid-Metabolizing Enzyme Cytochrome P450 26a1 (Cyp26a1) Is Essential for Implantation: Functional Study of Its Role in Early Pregnancy
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视黄酸代谢酶细胞色素 P450 26a1 (Cyp26a1) 对于着床至关重要：其在早期妊娠中的作用的功能研究
DOI：
10.1002/jcp.22056
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发表时间：
2010-05-01
影响因子：
5.6
通讯作者：
Peng, Jing-Pian
中科院分区：
文献类型：
--
作者：
Han, Bing-Chen;Xia, Hong-Fei;Peng, Jing-Pian
维生素A（VA）是胎儿正常发育和成功怀孕所必需的。怀孕期间摄入过量的VA可能会对母体和胎儿产生不良影响。细胞色素P45026 A1（cyp 26 a1）是维甲酸（RA）的代谢酶，参与VA的代谢。研究表明cyp 26 a1在女性生殖道，尤其是子宫中表达。为探讨cyp 26 a1在妊娠中的作用，构建了cyp 26 a1基因重组质粒DNA疫苗，并将其免疫小鼠。与对照组相比，cyp 26 a1质粒免疫小鼠的妊娠率显著降低（P < 0.01）。进一步的研究结果表明，cyp 26 a1 mRNA和蛋白在着床期子宫中被特异性诱导表达，并定位于子宫腔上皮。重要的是，在妊娠第3天子宫注射cyp 26 a1特异性反义寡核苷酸或抗cyp 26 a1抗体后，着床位点的数量也显著减少（P < 0.05）。宫腔注射后，RA相关细胞维甲酸结合蛋白1和组织转氨酶的表达明显增加（P < 0.05）。这些数据表明，子宫cyp 26 a1活性是重要的维持妊娠，特别是在胚泡植入的过程中。J.细胞。223：471-479，2010。(C)2010 Wiley-Liss，Inc.
Vitamin A (VA) is required for normal fetal development and successful pregnancy. Excessive VA intake during pregnancy may lead to adverse maternal and fetal effects. Cytochrome P450 26A1 (cyp26a1), a retinoic acid (RA)-metabolizing enzyme, is involved in VA metabolism. It has been shown that cyp26a1 is expressed in female reproductive tract, especially in uterus. In order to investigate the role of cyp26a1 during pregnancy, we constructed a recombinant plasmid DNA vaccine encoding cyp26a1 protein and immunized mice with the plasmid. Compared to control groups, the pregnancy rate of the cyp26a1 plasmid-immunized mice were significantly decreased (P < 0.01). Further results showed that both cyp26a1 mRNA and protein were specifically induced in the uterus during implantation period and localized in the uterine luminal epithelium. Importantly, the number of implantation sites was also significantly reduced (P < 0.05) after the uterine injection of cyp26a1-specific antisense oligos or anti-cyp26a1 antibody on day 3 of pregnancy. Accordingly, the expression of RA-related cellular retinoic acid binding protein 1 and tissue transglutaminase was markedly increased (P < 0.05) in the uterine luminal epithelium after intrauterine injection treatments. These data demonstrate that uterine cyp26a1 activity is important for the maintenance of pregnancy, especially during the process of blastocyst implantation. J. Cell. Physiol. 223: 471-479, 2010. (C) 2010 Wiley-Liss, Inc.