Oral Presentation ESA-SRB-NZSE-CaSR 2026 in conjunction with ENSA

Elevated decidual vascular remodelling and placental efficiency is elicited by maternal-fetal MHC disparity and mediated by maternal T cells (142592)

Uyen Pham 1 , Hon (Dexter) Chan 1 , Kerrie Foyle 1 , Ethel Adap 1 , Alison S Care 1 , Sarah A Robertson 1
  1. The Robinson Research Institute, School of Pharmacy and Biomedical Science, College of Health, Adelaide University, Adelaide

1.Background

Regulatory T (Treg) cells are essential for maternal immune tolerance of paternally-inherited major histocompatibility complex (MHC) and minor histocompatibility (MiHC) antigens expressed by the conceptus and also facilitate decidual vascular remodelling to support placentation and fetal growth (1). Disparity in parental MHC antigens promotes fetal growth and pregnancy outcomes, but whether decidual vascular remodelling mediates this effect is not clear.

2.Methods

C57BL/6 (T cell-replete) and Rag1-/- (T cell-deficient) female mice were mated with C57BL/6 (MHC&MiHC-matched), Balb/b (MHC-matched,MiHC-disparate) and Balb/c (MHC&MiHC-disparate) males, and pregnancy outcomes were evaluated on gestational day (gd) 17.5 (n=14-17 dams/group). In another cohort, decidual vascular adaptation was evaluated at gd10.5 by histological analysis (n=7-9 dams/group).

3.Results

Balb/b and Balb/c-mated dams had reduced fetal loss (p<0.01) and elevated fetal and placental weights than C57BL/6-mated dams (p<0.001), but the fetal-to-placental weight ratio was 11% higher in Balb/c than in Balb/b matings. Histological analysis of mid-sagittal placental sections revealed a larger labyrinth and junctional zone (p<0.05) in Balb/b than in Balb/c matings, indicating greater placental efficiency when parental MHC&MiHC are disparate. At gd10.5, greater spiral artery remodelling was evident in Balb/c-mated dams, with a 1.8- and 1.5-fold increase in lumen area compared to C57BL/6- and Balb/b-mated dams (both p<0.001). α-smooth muscle actin (α-SMA) retention was also reduced in Balb/c matings (p<0.001). However, the effects of parental MHC disparity on placental efficiency and decidual artery remodelling were absent in Balb/c-mated T cell-deficient Rag1-/- dams. 

4.Conclusion

These findings demonstrate that parental MHC disparity maximises pregnancy outcomes by optimising decidual spiral artery remodelling to improve placental efficiency, and that maternal T cells are required to elicit this benefit. This underscores the significance of maternal T cells in decidual vascular adaptation required for robust placentation and importantly shows that T cells are responsible for mediating the reproductive benefits conferred by parental MHC disparity.

  1. Hosking, S.L., Moldenhauer, L.M., Tran, H.M., Chan, H.Y., Groome, H.M., Lovell, E.A.K., Green, E.S., O’Hara, S.E., Roberts, C.T., Foyle, K.L., Davidge, S.T., Robertson, S.A. and Care, A.S. (2024) 'Treg cells promote decidual vascular remodeling and modulate uterine NK cells in pregnant mice', JCI Insight, 10(2), available: http://dx.doi.org/10.1172/jci.insight.169836.