Zheng W L, Ong D E
Department of Biochemistry, Vanderbilt School of Medicine, Nashville, Tennessee 37232, USA.
Biol Reprod. 1998 Apr;58(4):963-70. doi: 10.1095/biolreprod58.4.963.
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 the uterus during pregnancy. In this study we describe the pattern of temporal and cell-specific expression of cellular retinol-binding protein (CRBP) and cellular retinoic acid-binding proteins type I and type II (CRABP and CRABP[II], respectively) in the rat uterus during the periimplantation period (Day 1 to Day 7 of pregnancy; Day 1 = presence of vaginal plug). Immunohistochemical studies showed that there were dramatic and rapid changes in expression pattern of the retinoid-binding proteins after mating as early as Day 1, as well as a differential expression 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 localized to the luminal epithelium at Day 1, being stronger on the mesometrial side, and then fell to lower levels. CRBP was also expressed in the luminal epithelium on the mesometrial side at Day 1 as well as in some stromal cells, declining at these sites over the next several days. CRABP was localized to some of the stromal cells at Day 1, overlapping CRBP expression. Embryonic implantation was accompanied by the appearance of CRBP and CRABP(II) in the decidual cells. CRBP and CRABP were also present in both smooth muscle layers of the uterus. The changes in the temporal and cell-specific distribution of retinoid-binding proteins imply a multifunctional role of vitamin A in uterine cell proliferation, differentiation, and embryonic implantation. The presence of CRABP(II) suggests that local generation of retinoic acid is important in these processes.
视黄酸可能是天然存在的类视黄醇（视黄醇及其衍生物）中最具活性的激素形式，在体内对于维持正常妊娠和胚胎发育是必需的。然而，关于孕期子宫内视黄酸的具体作用位点和代谢情况却知之甚少。在本研究中，我们描述了大鼠子宫在植入前期（孕期第1天至第7天；第1天 = 出现阴道栓）细胞视黄醇结合蛋白（CRBP）以及Ⅰ型和Ⅱ型细胞视黄酸结合蛋白（分别为CRABP和CRABP[II]）的时间和细胞特异性表达模式。免疫组织化学研究表明，早在交配后的第1天，类视黄醇结合蛋白的表达模式就发生了显著而迅速的变化，并且在植入前期检查子宫系膜侧和反子宫系膜侧时，这些蛋白存在差异表达。CRABP(II)的存在先前已被证明与子宫上皮中的视黄酸合成相关，在第1天特异性定位于腔上皮，在子宫系膜侧更强，随后降至较低水平。CRBP在第1天也表达于子宫系膜侧的腔上皮以及一些基质细胞中，在接下来的几天里这些部位的表达下降。CRABP在第1天定位于一些基质细胞，与CRBP的表达重叠。胚胎着床伴随着蜕膜细胞中CRBP和CRABP(II)的出现。CRBP和CRABP也存在于子宫的两层平滑肌中。类视黄醇结合蛋白在时间和细胞特异性分布上的变化意味着维生素A在子宫细胞增殖、分化和胚胎着床中具有多功能作用。CRABP(II)的存在表明视黄酸的局部生成在这些过程中很重要。
