title: Cytochrome P450 26A1 modulates natural killer cells in mouse early pregnancy.
abstract: Cytochrome P450 26A1 (CYP26A1) has a spatiotemporal expression pattern in the uterus, with a significant increase in mRNA and protein levels during peri-implantation. Inhibiting the function or expression of CYP26A1 can cause pregnancy failure, suggesting an important regulatory role of CYP26A1 in the maintenance of pregnancy. However, little is known about the exact mechanism involved. In this study, using a pCR3.1-cyp26a1 plasmid immunization mouse model and a Cyp26a1-MO (Cyp26a1-specific antisense oligos) knockdown mouse model, we report that the number of Dolichos biflorus agglutinin (DBA) lectin-positive uterine natural killer (uNK) cells was reduced in pCR3.1-cyp26a1 plasmid immunized and Cyp26a1-MO-treated mice. In contrast, the percentage of CD3-CD49b+NK cells in the uteri from the treatment group was significantly higher than that of the control group in both models. Similarly, significantly up-regulated expression of CD49b (a pan-NK cell marker), interferon gamma, CCL2, CCR2 (CCL2 receptor) and CCL3 were detected in the uteri of pCR3.1-cyp26a1- and Cyp26a1-MO-treated mice. Transcriptome analysis suggested that CYP26A1 might regulate NK cells through chemokines. In conclusion, the present data suggest that silencing CYP26A1 expression/function can decrease the number of uNK cells and significantly increase the percentage of CD3-CD49b+NK cells in the uteri of pregnant mice. These findings provide a new line of evidence correlating the deleterious effects of blocking CYP26A1 in pregnancy with the aberrant regulation of NK cells in the uterus.
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Chao-Yang
authors.initials: CY
authors.lastname: Meng
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Zhong-Yin
authors.initials: ZY
authors.lastname: Li
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Wen-Ning
authors.initials: WN
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Zhi-Hui
authors.initials: ZH
authors.lastname: Song
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Li
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Jing-Pian
authors.initials: JP
authors.lastname: Peng
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D002452:Cell Count; D018925:Chemokines / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D007114:Immunization; D007694:Killer Cells, Natural / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D060172:Morpholinos / Q000494:pharmacology; D010957:Plasmids / Q000378:metabolism; D011247:Pregnancy; D015203:Reproducibility of Results; D000072516:Retinoic Acid 4-Hydroxylase / Q000378:metabolism*; D014599:Uterus / Q000166:cytology
chemical_list: D000906:Antibodies; D018925:Chemokines; D060172:Morpholinos; D000072516:Retinoic Acid 4-Hydroxylase
keywords: CYP26A1; chemokines; implantation; natural killer cells