The observations we have reported here indicate that the local generation of retinoic acid is an important signal in the preparation of the uterus for implantation of the embryo. Although we did not determine retinoic acid production directly, we believe that we can infer, from the expression of CRABP(II) in certain cells, that those cells are producing retinoic acid as a paracrine, and perhaps, autocrine hormone. This inference is based on our previous work with the pseudopregnant rat model. We established that uterine epithelial cells synthesize retinoic acid in culture only if isolated at the time of CRABP(II) expression. That such retinoic acid synthesis also occurs in the intact animal was verified by the demonstration that high levels of retinoic acid could be extracted from isolated uteri only at the time when CRABP(II) was expressed. Thus, we assume that the same correlation between CRABP(II) expression and retinoic acid synthesis exists for the uterus of the pregnant animal. birth control pills

In the normally cycling animal, CRABP(II) is present in the uterine epithelium primarily at the estrous stage, declining quickly when estrus ends. It was interesting to see that as rapidly as 1 day after mating, retinoid processing in the uterus had already responded to the new physiological state. Instead of the decline that would have been observable by this time in an unmated animal, the level of CRABP(II) had actually increased. This increase was seen only on the mesometrial side, an asymmetry never observed for the uterus at estrus. Coincident with this was the coexpression of CRBP, the carrier of the retinol that is the precursor of retinoic acid synthesis. This suggests that the retinoic acid signal is part of the mechanism by which the uterus prepares for the coming implantation.