The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Regulatory T cells protect against fetal loss in pregnancies compromised by peri-implantation disruption of progesterone signalling (#377)

Ella Green 1 , Lachlan Moldenhauer 1 , Shaun McColl 2 , Sarah Robertson 1
  1. Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia
  2. School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia

Early pregnancy is characterised by adaptations in the maternal immune system to allow development of genetically disparate embryos. Immune tolerance is mediated by a subset of anti-inflammatory, homeostatic T cells known as regulatory (Treg) cells, and is influenced by maternal hormones, through mechanisms that are not well understood. We previously demonstrated a key role for P4 in regulating Treg cell abundance and phenotype in early pregnancy, using a mouse model of peri-implantation disruption in P4 signalling with the P4-receptor antagonist, RU486. Administration of low-dose RU486 (1 mg/kg) on day (d) 1.5 and 3.5 post-coitus (pc) to allogeneically mated C57Bl6 females caused a decreased Treg cell pool in mid-pregnancy, followed by a reduced pregnancy rate in late pregnancy (d18.5 pc) along with increased fetal resorptions. Here, we investigated the effect of transferring donor Treg cells to RU486-treated females. CD4+CD25+ Treg cells (or vehicle control) isolated from pregnant females (d11.5- d14.5 pc) were transferred intravenously on d3.5 pc to mated recipients treated with RU486. Strikingly, the reduced pregnancy rate was rescued in RU486-treated females administered Treg cells. Furthermore, Treg cell transfer to RU486-treated females restored fetal viability to levels comparable to control-treated females. In another group naïve/effector T cells (CD4+CD25-) were administered, and although pregnancy rate was improved, the number of viable pups per litter was reduced and fetal resorption was elevated compared to control-treated and Treg cell-treated females. This data shows that Treg cells can rescue pregnancy outcome in females where Treg cells are insufficient due to peri-implantation P4 signalling disruption. This demonstrates that P4 is a key determinant of Treg cells in pregnancy and that Treg cells are a key effector mechanism for P4 actions. Luteal phase and early pregnancy P4 is thus essential to prime Treg cells to drive a robust anti-inflammatory immune response necessary for optimal pregnancy success.