Retinoic acid-metabolizing enzyme cytochrome P450 26a1 (cyp26a1) is essential for implantation: functional study of its role in early pregnancy.
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.
Han
Bing-Chen
BC
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Xia
Hong-Fei
HF
Sun
Jing
J
Yang
Ying
Y
Peng
Jing-Pian
JP
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D010064:Embryo Implantation / Q000502:physiology*; D004717:Endometrium / Q000166:cytology / Q000201:enzymology*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D000072516:Retinoic Acid 4-Hydroxylase; D011503:Transglutaminases / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism*; D019444:Vaccines, DNA / Q000494:pharmacology
D019138:Antibodies, Blocking; D065607:Cytochrome P-450 Enzyme Inhibitors; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D019444:Vaccines, DNA; C082927:retinoic acid binding protein I, cellular; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; C000607080:Cyp26a1 protein, mouse; D000072516:Retinoic Acid 4-Hydroxylase; D011503:Transglutaminases; C105804:transglutaminase 1