Estrogen-regulated Expression and Distribution of Id-1 in the Mouse Uterus

Id genes are involved in proliferation and differentiation in various cell types. However, it remains to be fully investigated how Id genes are regulated in highly dynamic uterine tissue. Using cDNA microarray, we previously observed that Id-1 was upregulated in uteri from ovariectomized (OVX) mice exposed to 17β-estradiol (E2). Here, we further examined the expression pattern of Id-1 and its regulation of by E2 and progesterone (P4) in the mouse uterus. Increased Id-1 transcripts in OVX mice uterus exposed to E2 were efficiently reduced by pretreatment with ICI 182,780 (an antagonist for nuclear estrogen receptor), suggesting that E2 induced expression of Id-1 is mediated via classical estrogen receptor (ER). In contrast, P4 treatment did not enhance or antagonize the action of E2 on Id-1 expression. Laser capture microdissection revealed that Id-1 is exclusively expressed in luminal epithelial cells. Notably, Id-1 was significantly upregulated at implantation sites on day 4.5 of pregnancy due to strong expression of Id-1 in blastocyst stage embryos. The present results show that the expression of Id-1 in the mouse uterus is tightly regulated by E2 via classical ER genomic pathway, not P4 suggesting an important role in uterine physiological events such as the estrous cycle and implantation process.