Estradiol-regulated proline-rich acid protein 1 is repressed by class I histone deacetylase and functions in peri-implantation mouse uterus.

Secretory protein proline-rich acid protein 1 (PRAP1) is abundantly expressed in late pregnant uterus. However, regulation and function of PRAP1 in pregnant uterus is still elusive. We firstly reported differential expression of PRAP1 in peri-implantation uteri and its localization in endometrial epithelia. Expression of PRAP1 in uterus was induced by 17ß-estradiol and its expression showed a negative correlation with that of class Ihistone deacetylases (HDACs) in isolated endometrial epithelia. PRAP1 was increased by HDACs inhibitor sodium butyrate treatment, while decreased significantly by estrogen receptor inhibitor ICI182,780 via up-regulating class IHDACs. Number of implanted embryos was decreased in mice immunized with pCR3.1-PRAP1 or injected with rabbit anti-PRAP1 antibody. DNA immunization or antibody injection could affect apoptosis and expression of cytokines (IL-4, IFN-γ). In conclusion, both 17ß-estradiol and class IHDACs are involved in modulating PRAP1 expression in peri-implantation uteri. Preliminary functional research indicates that neutralizing PRAP1 protein causes reduction of implanted embryos.

Effects of TGF beta-1 on mouse embryo implantation and expression of H2-D1 and H2-DM.

We investigated the mechanism that TGF-beta1 influences the immuno-environment at maternal-fetal interface and affects embryo implantation, using mouse uterine horn injection model. The expression of MHC I antigen (H2-D1) and the chaperone of MHC II antigen (H2-DM) after anti-TGF-beta1 antibody or hrTGF-beta1 treated pregnant mice were examined by real-time PCR, western blotting and immunohistochemistry. The results showed that the number of implanted embryos of anti-TGF-beta1 antibody-treated mice was decreased compared with the control. The expression of H2-D1 and H2-DM on days 6 and 7 treated uteri was increased both at mRNA and protein levels. In hrTGF-beta1 treated group, the expression of H2-D1 and H2-DM protein was decreased, and the number of implanted embryos was slightly increased. Immunohistochemical studies revealed that H2-D1 and H2-DM were mainly localized to the primary decidual zone. The anti-TGF-beta1 antibody and exogenous hrTGF-beta1 treatment altered the intensity of H2-D1 and H2-DM signal but did not change their localization. These observations suggested that injection of anti-TGF-beta1 antibody affected the number of mouse embryo implantation, and regulated the expression of H2-DM and H2-Q10.