Desmosomes are reduced in the mouse uterine luminal epithelium during the preimplantation period of pregnancy: a mechanism for facilitation of implantation.

Dynamic regulation of intercellular junctions is an essential aspect of many developmental, reproductive, and physiological processes. We have shown that expression of the desmosomal protein desmoplakin decreases in the luminal uterine epithelium during the preimplantation period of pregnancy in mice. By the time of implantation (between Days 4.5 and 5 of pregnancy), desmoplakin protein can barely be detected by SDS-PAGE and Western blotting, and by immunocytochemistry, it is restricted to well-spaced, punctate dots at the apicolateral junction. Using confocal XZ series and electron microscope quantitation, both the density and distribution of desmosomes along the lateral cell surfaces of luminal epithelial cells were observed to change during early pregnancy. On Day 1 of pregnancy, desmosomes were found at high density in the apicolateral junctional complex, being present here in 79% of ultrathin sections examined, whereas on Day 5, the density was much reduced (present in only 18% of ultrathin sections examined). Desmosomes were found along the lateral surfaces, at or below the level of the nucleus, in 15% of ultrathin sections examined on Day 1 of pregnancy but in only 1% on Day 5. Desmoplakin mRNA declined during the first 4-5 days of pregnancy, along with the protein, suggesting that these changes are controlled at the level of mRNA. This study shows that desmosomes are regulated during early pregnancy, and we propose that a reduction in desmosome adhesion facilitates penetration of the luminal epithelium by trophoblast cells at implantation.

Demonstration of oestrogenic control of H-type-1 carbohydrate antigen in the murine endometrial epithelium by use of ICI 182,780.

The carbohydrate H-type-1 antigen has been implicated in attachment of the murine blastocyst to the endometrial epithelium. Monoclonal antibody 667/9E9 was used to investigate the steroidal dependency of expression of this antigen in the murine endometrial epithelium using intact or ovariectomized mice treated with oestrogen or the pure anti-oestrogen, ICI 182,780. The effects of this anti-oestrogen were also investigated in the endometrial epithelium from intact rats. In both ovariectomized, oestrogen-supplemented and intact mice after treatment with ICI 182,780, staining with monoclonal antibody 667/9E9 was abolished in the luminal epithelium on both the apical and lateral cell surfaces, whereas basal staining remained. Glandular staining in mice was not affected in the same manner. In intact rats, where H-type-1 antigen expression has been reported to be predominantly controlled by progesterone, the anti-oestrogen had little effect, in accordance with previous reports.

Expression of carbohydrate antigens in the rat uterus during early pregnancy and after ovariectomy and steroid replacement.

Monoclonal antibodies were used to examine the expression of a number of carbohydrate antigens in the rat endometrial epithelium from day 1 to day 8 of pregnancy and in ovariectomized rats supplemented with ovarian steroids. Carbohydrate antigens based on the Gal beta 1-GlcNAc backbone structure were expressed and some of these (Le(y), Le(x), B antigen) were present at all stages of pregnancy and independent of ovarian steroids. The H-type-2 antigen was stimulated by progesterone and expressed in the sensitized and receptive uterus, but was not detected after implantation or, in ovariectomized rats, in the refractory phase. The H-type-1 antigen, which is stimulated by oestrogen in the mouse, appeared to be stimulated by progesterone in rats. It was expressed throughout the period of pregnancy but maximal expression was found on days 4-5. The histo-blood group A antigen appeared in ovariectomized rats only after treatment with progesterone followed by three daily injections of progesterone and oestrogen, and in the corresponding postimplantation period of pregnant rats. Its appearance corresponded to the loss of detectable H-type-2 antigen. This study shows that the rat endometrial epithelium expresses some carbohydrate antigens not expressed in mice (A and B antigen) or under completely different steroidal regulation (H-type-1). Moreover, the T antigen was expressed on the endometrial epithelium adjacent to decidua on days 7 and 8 of pregnancy, but not in rats given ovarian steroids to mimic the sensitized, receptive or refractory phase. Differences in expression between glandular and luminal epithelial indicated differences in steroidal regulation, as found in mice.