Year-end Sale % OFF 
Abstract
Immune tolerance at the fetomaternal interface must be established during the processes of implantation and pregnancy. Monoclonal nonspecific suppressor factor beta (MNSFβ) is a secreted protein that possesses antigen-nonspecific immune-suppressive function. It was previously reported that intrauterine immunoneutralization of MNSFβsignificantly inhibited embryo implantation in mice. In the present study, MNSFβprotein expression was up- or downregulated by overexpression or RNA interference, respectively, in HCC-94 cells and the culture supernatants used to determine effects of MNSFβon the secretion of IL-4 and TNFαfrom mouse lymphocytes as detected by ELISA. A coculture model of mouse embryos and endometrial stromal cells was also utilized to determine the effects of a specific anti-MNSFβantibody on hatching and growth of embryosin vitro. The results show that MNSFβinduced secretion of IL-4 and inhibited secretion of TNFαfrom mouse lymphocytes. Following immunoneutralization of MNSFβprotein in the HCC-94 supernatant, the stimulatory effect of MNSFβon IL-4 secretion from mouse lymphocytes was reduced, while the inhibitory effect on secretion of TNFαwas abrogated. Expression of MNSFβwas detected in both embryonic and endometrial stromal cells, and its immunoneutralization inhibited the hatching and spreading of embryos in anin vitrococulture model. These results indicated that MNSFβmay play critical roles during the peri-implantation process by regulating cytokine secretion of lymphocytes and by mediating the crosstalk between embryonic cells and endometrial stromal cells.
Highlights
In most mammals, the process of implantation, during which an early embryo must attach to and invade the maternal endometrium, is a critical step for successful pregnancy [1]
Immunohistochemistry and western blotting demonstrated that MNSFβ expression plasmids (MNSFβ) protein was abundantly expressed by HCC-94 cells and mouse uterine endometrial stromal cells (Figure 2, HCC, En) and no positive signal was detected in the mouse lymphocytes (Figure 2, Lym)
This study demonstrates a stimulatory effect of MNSFβ on the secretion of IL-4 from mouse lymphocytes, as well as an inhibitory effect on their secretion of TNFα
Summary
The process of implantation, during which an early embryo must attach to and invade the maternal endometrium, is a critical step for successful pregnancy [1]. As the embryo is a semi-allograft to the maternal uterus, special immunotolerance must be established at the fetomaternal interface to allow the normal development of the fetus during the peri-implantation and subsequent pregnancy processes [2]. Monoclonal nonspecific suppressor factor (MNSF) was originally identified as a specific cytokine that could moderate the immune response by inhibiting the proliferation of T and B cells [6, 7] and by regulating cytokine secretion by T cells [8, 9]. Immunoneutralization of endometrial MNSFβ in vivo with a specific anti-MNSFβ antibody significantly inhibited mouse embryo implantation, potentially by disturbing fetomaternal immune tolerance, trophoblast invasion, or embryonic development [12], calling for the further investigation
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
