Oocyte donation pregnancies with high fetal-maternal immunogenetic dissimilarity show alterations in the maternal peripheral immunoregulatory response

Oocyte donation (OD) pregnancies result in increased fetal-maternal immunogenetic dissimilarity due to paternal and donor-derived genes. Higher fetal-maternal HLA mismatches are correlated with preeclampsia. Therefore, this study explored the maternal immune response, focusing on regulatory T cells (Tregs) during low versus high allogeneic pregnancies, and healthy versus preeclamptic OD pregnancies. Ten healthy and five preeclamptic OD pregnancies were included. Maternal peripheral blood was collected at different stages of pregnancy. Fetalmaternal HLA mismatches were determined, and immunophenotyping of peripheral blood mononuclear cells was conducted using a 22-colour spectral flow cytometry panel. Cytokines and hormones were detected in maternal plasma using ELISA and Luminex assays. The findings show similarities, but also distinct differences between low and high allogeneic healthy OD pregnancies. Early high allogeneic OD pregnancy showed reduction in Tregs, and CD8+ T cells, alongside lower percentage of effector/memory Tregs expressing PD-1 and Helios. Additionally, high allogeneic OD pregnancies showed increased IL-6 and progesterone in the first trimester. These variations suggest a different mode of immune regulation in early high allogeneic OD pregnancies, possibly to maintain healthy pregnancy. Further comparative analyses revealed reduced CD45RO+CTLA-4+ Tregs and increased latent TGF-(31 and -(32 levels in early preeclamptic compared to healthy OD pregnancy. Latestage preeclamptic OD pregnancies exhibited higher frequencies of CD45RO+TIGIT+ Tregs and higher levels of TNF alpha, indicating both a regulatory and pro-inflammatory environment. Overall, this study sheds light on the course of various immunoregulatory key players in OD pregnancy, and expands knowledge on maternal tolerance in this particular type of pregnancy.