| First Author | Yull S | Year | 2023 |
| Journal | Front Immunol | Volume | 14 |
| Pages | 1276979 | PubMed ID | 38022561 |
| Mgi Jnum | J:343235 | Mgi Id | MGI:7563055 |
| Doi | 10.3389/fimmu.2023.1276979 | Citation | Yull S, et al. (2023) Uterine Nodal expression supports maternal immunotolerance and establishment of the FOXP3(+) regulatory T cell population during the preimplantation period. Front Immunol 14:1276979 |
| abstractText | Pregnancy success is dependent on the establishment of maternal tolerance during the preimplantation period. The immunosuppressive function of regulatory T cells is critical to limit inflammation arising from implantation of the semi-allogeneic blastocyst. Insufficient maternal immune adaptations to pregnancy have been frequently associated with cases of female infertility and recurrent implantation failure. The role of Nodal, a secreted morphogen of the TGFbeta superfamily, was recently implicated during murine pregnancy as its conditional deletion (Nodal(Delta/Delta)) in the female reproductive tract resulted in severe subfertility. Here, it was determined that despite normal preimplantation processes and healthy, viable embryos, Nodal(Delta/Delta) females had a 50% implantation failure rate compared to Nodal(loxP/loxP) controls. Prior to implantation, the expression of inflammatory cytokines MCP-1, G-CSF, IFN-gamma and IL-10 was dysregulated in the Nodal(Delta/Delta) uterus. Further analysis of the preimplantation leukocyte populations in Nodal(Delta/Delta) uteri showed an overabundance of infiltrating, pro-inflammatory CD11b(high) Ly6C(+) macrophages coupled with the absence of CD4(+) FOXP3(+) regulatory T cells. Therefore, it is proposed that uterine Nodal expression during the preimplantation period has a novel role in the establishment of maternal immunotolerance, and its dysregulation should be considered as a potential contributor to cases of female infertility and recurrent implantation failure. |
