Peripheral monocyte subsets are altered during gestation in oocyte donation pregnancy complicated with pre-eclampsia.

Abstract

Oocyte donation (OD) pregnancies show a higher fetal-maternal incompatibility and a higher risk of developing pre-eclampsia (PE) than autologous pregnancies. As maternal monocytes play a role in the tolerization of the allogeneic fetus, the aim of this study was to analyse monocyte phenotypes in healthy and PE OD pregnancies. We collected maternal peripheral blood at different gestational time points in healthy (n = 10) and PE (n = 5) OD pregnancies. Fetal-maternal human leukocyte antigen (HLA) mismatches were calculated. We used a 35-colour antibody panel for Aurora spectral flow cytometry to analyse the composition and surface marker expression of monocyte subsets. Expression of CD38 on intermediate monocytes significantly increased throughout gestation in healthy OD pregnancies. Compared with the healthy group, the PE group exhibited even higher CD38 expression on monocyte subsets, with statistical significance. Immune inhibiting receptors CD85j (LILRB1) and CD85d (LILRB2), as well as monocyte recruitment regulating molecules CCR2 and CD91, also showed significantly enhanced expression on monocyte subsets during PE. When comparing healthy and PE OD only in pregnancies with high HLA mismatches, the different CD38 and CD85j expression in monocyte subsets was still significant. In conclusion, in healthy OD pregnancies, the upregulated CD38 expression might reflect a proinflammatory condition specifically at the third trimester. In PE OD pregnancies, expression of both inflammatory and immune regulatory markers is increased in maternal peripheral monocyte subsets. The elevated expression of CCR2 and CD91 on these subsets might reflect monocyte chemotaxis and the effect from systemic vascular dysfunction at the late stage of PE.