Background: The immune system is essential for remodelling reproductive tissues to support embryo implantation, placental development, and fetal growth. Seminal fluid is a key regulator of pregnancy-associated immune adaptations. We previously showed that seminal fluid rapidly expands uterine gamma delta (γδ) T cells in mice. Although γδ T cells are abundant at mucosal sites and contribute to host defence and tissue homeostasis, their role in fertility and pregnancy is poorly understood.
Methods: To determine the contribution of γδ T cells to pregnancy, transgenic Tcrd-GDL mice were administered diphtheria toxin (15 ng/g, intraperitoneally) at 0.5 and 2.5 days post-coitus (dpc) to specifically deplete γδ T cells, with PBS-treated mice as controls. Depletion was confirmed by flow cytometry at 3.5 dpc (n=5–6/group) and persisted into late gestation. Pregnancy outcomes were assessed at 17.5 dpc in another cohort (n=9–12/group).
Results: Early pregnancy γδ T cell depletion did not significantly alter pregnancy rate, litter size, fetal viability, or resorption rate. However, mean fetal weight was reduced by 11.2% in dams depleted of γδ T cells compared with controls (P<0.01), without affecting placental weight. This effect was driven by a subset of γδ T cell-depleted dams, with 3/9 pregnancies displaying marked fetal growth restriction. Overall, 34.8% of fetuses from γδ T cell-depleted dams (24/69) fell below the 10th percentile of fetal weight for the control group. Severe developmental delay was also observed in 2/8 fetuses from a γδ-depleted dam.
Conclusion: These findings provide the first evidence that γδ T cells promote optimal fetal growth. Ongoing studies are investigating how disrupting the early gestational γδ T cell response alters immune adaptation to pregnancy and whether γδ T cells contribute to maternal quality-control mechanisms that influence offspring developmental outcomes.