Parental genetic disparity can improve reproductive outcomes and could have significant implications for human reproductive health, agriculture industries, and endangered species conservation. The most polymorphic antigens expressed by the fetus and the placenta are encoded by major and minor histocompatibility complex (MHC and MiHC) genes. These paternally-derived antigens appear to interact with maternal T cells and induce expansion of the regulatory T cell pool to facilitate placental development and ultimately affect pregnancy outcomes, although the specific undelying mechanisms are undefined.
We hypothesized that maternal T cells are essential for imparting the benefits of MHC-disparity on pregnancy outcome. Utilizing T cell-sufficient C57Bl/6 and T cell-deficient Rag1-null mutant (Rag1-/-) female mice, fetal and placental development were assessed in late-gestation day 17.5 post-coitum following mating with C57Bl/6 (MHC, MiHC-matched), Balb/b (MHC-matched, MiHC-disparate), or Balb/c (MHC, MiHC-disparate) males.
When pregnancies in C57Bl/6 females were sired by either Balb/b or Balb/c males there was a 18% reduction in fetal resorption rate and increased fetal weight compared to C57Bl/6-sired pregnancies. Balb/c-mated dams exhibited 11% higher fetal:placental weight ratio compared to Balb/b-mated dams (n=15-17/group, P<0.001). This suggested a potential compensatory placental development mechanism in Balb/b-mated dams to achieve the same fetal growth as Balb/c-mated dams, indicating more efficient female reproductive resource investment with parental MHC and MiHC disparity. In T cell-deficient Rag1-/- dams, resorption rate was comparable in all mating groups. Neither fetal resorption nor fetal:placental weight ratio were attenuated by MHC disparity as observed in C57Bl/6 dams, although increased fetal and placental weight were still evident.
These findings demonstrate a crucial role for maternal T cells in imparting normal fetal and placental development in MHC/MiHC-disparate pregnancies. Additional experiments to investigate the impact of parental histocompatibility on the regulation of specific maternal T cell subsets and placentation are underway.