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Retinoic Acid Synthesis and Expression of Cellular Retinol-Binding Protein and Cellular Retinoic Acid-Binding Protein Type II Are Concurrent with Decidualization of Rat Uterine Stromal Cells¹

Departments of Biochemistry (W.L.Z., D.E.O.), Obstetrics and Gynecology (E.S.R., K.G.O.), and Cell Biology (J.L.), Vanderbilt School of Medicine, Nashville, Tennessee 37232

Address all correspondence and requests for reprints to: David E. Ong, Ph.D., Department of Biochemistry, 610 MRB-I, Vanderbilt University School of Medicine, Nashville, Tennessee 37232. E-mail: david.e.ong{at}vanderbilt.edu

Decidualization of stromal cells at the site of embryo implantation in the rat uterus is accompanied by expression of cellular retinol-binding protein and cellular retinoic acid-binding protein [CRABP(II)], whose presence has been shown to correlate with gain of ability to synthesize retinoic acid in other cells. Here we examined whether decidual cells also acquired the ability to synthesize retinoic acid, which would have important implications for understanding the implantation process. Decidual cells were isolated from the uterus on day 8 of pregnancy and cultured. When provided with retinol, they indeed synthesized and released retinoic acid to the medium. To follow acquisition of this ability more closely, artificial induction of decidualization was exploited. Ovariectomized rats were placed on a hormonal regimen that allows decidualization to occur in vivo, with oil stimulation, or in vitro, if cells are isolated on day 5 of the regimen and then cultured. Decidualization in vivo reproduced the expression of cellular retinol-binding protein and CRABP(II) seen during pregnancy. Stromal cells isolated on regimen day 2 synthesized little retinoic acid and expressed little alkaline phosphatase, a marker of decidualization. Stromal cells isolated on regimen day 5 had elevated levels of alkaline phosphatase, increasing during the 3 days of culture examined. The ability of the stromal cells to synthesize retinoic acid showed the same pattern: a substantially elevated production from that previously observed, on day 2, with production increasing significantly over the next 2 culture days. Thus, expression of CRABP(II) was correlated with gain of ability to synthesize retinoic acid. Retinoid signaling may be an important part of the process of embryo implantation.

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