Expression and steroid hormonal control of Muc-1 in the mouse uterus

Abstract

Previous studies from our laboratory established that large M(r) mucin glycoproteins are major apically disposed components of mouse uterine epithelial cells in vitro. The present studies demonstrate that Muc-1 represents one of the apically disposed mucin glycoproteins of mouse uterine epithelia, and that Muc-1 protein and messenger RNA (mRNA) expression are regulated in the periimplantation mouse uterus by ovarian steroids. Muc-1 expression is exclusive to the epithelial cells of the uterus under all conditions examined. Muc-1 expression is high in the proestrous and estrous stages and decreases during diestrous. Both Muc-1 protein and mRNA decline to barely detectable levels by day 4 of pregnancy, i.e. before the time of blastocyst attachment. In contrast, Muc-1 expression in the cervix and vagina is maintained during this same period. Delayed implantation was established in pregnant mice by ovariectomy and maintained by the administration of exogenous progesterone (P). Initiation of implantation was triggered by coinjection of P-maintained mice with a nidatory dose of 17 beta-estradiol (E2). Muc-1 levels in the uterine epithelia of P-maintained mice declined to low levels similar to those observed on day 4 of normal pregnancy. Coinjection of E2 did not alter Muc-1 expression, suggesting that down-regulation of Muc-1 is a P-dominated event. This was confirmed in ovariectomized nonpregnant mice, which displayed stimulation of Muc-1 expression after 6 h of E2 injection. E2-Stimulated Muc-1 expression was inhibited by the pure antiestrogen, ICI 164,384. Although P alone had no effect on Muc-1 expression, it antagonized the action of E2. Injection of pregnant mice with the antiprogestin, RU486, a known implantation inhibitor, on day 3 of pregnancy restored high level expression of Muc-1 mRNA on day 4, indicating that down-regulation of Muc-1 is P receptor mediated. Collectively, these data indicate that Muc-1 expression in mouse uterine epithelium is strongly influenced by ovarian steroids. It is suggested that the loss of Muc-1 contributes to generation of a receptive uterine state.

Assessment of endometrial receptivity

“…In the mouse (and most mammals) MUC1 is considered a barrier to implantation and disappears at the time of implantation (81,82). MUC1 is expressed throughout the WOI in humans, and unique glycosylation patterns have been suggested as the explanation as to how MUC1 might be involved in endometrial receptivity (83)(84)(85) and are actively studied today.…”

MUC16 Is Lost from the Uterodome (Pinopode) Surface of the Receptive Human Endometrium: In Vitro Evidence That MUC16 Is a Barrier to Trophoblast Adherence1

“…Studies in mice report that the mucin disappears from the uterine surface at the receptive phase [15,17] and that the removal of the ectodomain of the mucin may be by the proteolytic action of TNF-converting enzyme (TACE), an extracellular metalloprotease-disintegrin tumor necrosis factor (TNF)-converting enzyme, also known as ADAM 17 [18]. In humans, there are contradictory reports that MUC1 is increased during the receptive phase [19], is lost from the uterodome surface [20,21] or, as shown using an in vitro technique, is lost locally in the region of the implanting blastocyst [22].…”

Progesterone regulation of glutathione S-transferase Mu2 expression in mouse uterine luminal epithelium during preimplantation period

“…Several antiadhesion molecules have been identified, including Muc1, Msx1, and Ihh. Muc1 is expressed in the mouse uterine epithelium before implantation (17). Msx1 is transiently expressed in the mouse uterine epithelium during the receptive period, but disappears at the time of blastocyst attachment or when the uterus enters the nonreceptive phase (26).…”

“…Pregnant mice on day 3 morning were subcutaneously injected with progesterone antagonist RU486 (0.4 mg/0.1 mL sesame oil) as described by Surveyor et al (17). Control mice received 0.1 mL sesame oil.…”