Regulation of sialomucin complex/Muc4 in the female rat reproductive tract

Sialomucin complex (SMC/rat Muc4) is a hetero-dimeric glycoprotein complex composed of an anti-adhesive mucin subunit ascites sialoglyco-protein (ASGP)-1 and a transmembrane subunit ASGP-2. SMC expression is tightly regulated in the uterus, and its expression appears to block blastocyst implantation. Expression is controlled by steroid hormone levels in the uterine luminal epithelium, but not the uterine glandular epithelium, oviduct, cervix or vagina. Increased progesterone levels lead to downregulation of SMC in the uterine luminal epithelium at the time of receptivity for implantation. Transforming growth factor β (TGF-β) has been implicated as a factor in uterine progesterone responses. Studies on primary rat uterine luminal epithelial cells showed that both SMC protein and transcript are downregulated by TGF-β1, although SMC expression is not altered by treatments with oestrogen or progesterone. SMC is also down-regulated when epithelial cells are co-cultured with isolated uterine stromal cells. Oestradiol and anti-TGF-β block the stromal cell effect. These data indicate that uterine epithelial cells respond to hormones to downregulate SMC via an indirect effect on stromal cells involving paracrine action of TGF-β.