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(127) CYP26A1 IS REQUIRED FOR PLACENTAL DEVELOPMENT. Tanaka, Satoshi1, Yan, Junli1, Ohgane, Jun1, Hattori, Naka1,2, Shiota, Kunio1, 1 Animal Resource Sci/Vet Med Sci, Tokyo, Japan2 Bio-oriented Technology Research Advancement Institution, Saitama, Japan ABSTRACT- Our previous study has shown that exogenous retinoic acid (RA) direct trophoblast cells to differentiate into trophoblast giant cells, suggesting that maternal RA from decidual tissue is potentially involved in the formation of giant cells during placentation. It is noteworthy that RA was capable of obstructing the differentiation inhibitory effect of FGF4 on the maintenance of stem cells in the culture of trophoblast stem (TS) cells. This anti-proliferative and/or differentiative effect of RA on TS cells indicates that maintenance of stem cells in early placentation might require a fine control of RA distribution in trophoblastic tissue in vivo. A RA-inactivating enzyme CYP26A1 is reported to play important roles in protecting certain embryonic tissues from inappropriate RA signaling. We show here that CYP26A1 is specifically expressed in extraembryonic ectoderm, a stem cell pool for the postimplantation trophoblast during placentation. In TS cells, CYP26A1 is expressed only in stem cell conditions, and loses its expression within 12 h upon differentiation induction by removal of FGF4 and embryonic fibroblast-conditioned medium. We further show that genetic ablation of CYP26A1 results in abnormal development of trophoblastic tissues, such as an overabundance of secondary giant cells and retarded formation of the chorion. These results define a novel role for CYP26A1 in protection of trophoblast stem cells from the deleterious effects of diffusible RA during placentation. Collectively, our results suggest that endogenous RA is one of the factors regulating placental development. KEY WORDS: Trophoblast stem (TS) cells, Placentation, Retionic acid, CYP26A1 |
