SPATIAL AND TEMPORAL PATTERNS OF EXPRESSION OF CELLULAR RETINOL-BINDING PROTEIN AND CELLULAR RETINOIC ACID-BINDING PROTEINS IN RAT UTERUS DURING EARLY-PREGNANCY

Retinoic acid, perhaps the most potent hormonal form of the naturally occurring retinoids (retinol and derivatives), is required in vivo for the maintenance of normal pregnancy and embryo development. However, little is known about the specific sites of action and metabolism in t he uterus during pregnancy. In this study we describe the pattern of t emporal and cell-specific expression of cellular retinol-binding prote in (CRBP) and cellular retinoic acid-binding proteins type I and type II (CRABP and CRABP[II], respectively) in the rat uterus during the pe riimplantation period (Day 1 to Day 7 of pregnancy; Day 1 presence of vaginal plug). Immunohistochemical studies showed that there were dram atic and rapid changes in expression pattern of the retinoid-binding p roteins after mating as early as Day 1, as well as a differential expr ession of these proteins when the mesometrial side and antimesometrial side of the uterus were examined during the periimplantation period. CRABP(II), whose presence has been previously shown to correlate with retinoic acid synthesis in the uterine epithelium, was specifically lo calized to the luminal epithelium at Day 1, being stronger on the meso metrial side, and then fell to lower levels. CRBP was also expressed i n the luminal epithelium on the mesometrial side at Day 1 as well as i n some stromal cells, declining at these sites over the next several d ays. CRABP was localized to some of the stromal cells at Day 1, overla pping CRBP expression. Embryonic implantation was accompanied by the a ppearance of CRBP and CRABP(II) in the decidual cells. CRBP and CRABP were also present in both smooth muscle layers of the uterus. The chan ges in the temporal and cell-specific distribution of retinoid-binding proteins imply a multifunctional role of vitamin A in uterine cell pr oliferation, differentiation, and embryonic implantation. The presence of CRABP(II) suggests that local generation of retinoic acid is impor tant in these processes.