Pregnancy Close to the Edge: An Immunosuppressive Infiltrate in the Chorionic Plate of Placentas from Uncomplicated Egg Cell Donation

Abstract

In pregnancies achieved after egg donation (ED) tolerance towards a completely allogeneic fetus is mediated by several complex immunoregulatory mechanisms, of which numerous aspects are still unknown. A distinct lesion not described previously in the literature, was repeatedly found in the chorionic plate in a substantial portion of placentas from ED pregnancies, but never in placentas from normal term pregnancies. The aim of this study was to assess its origin and its cellular composition. The relation between the lesion, the clinical and histological parameters were assessed. In addition we investigated the relation with the number of HLA-mismatches and KIR genotype of mother and child. In ten out of twenty-six (38.5%) placentas from ED pregnancies an inflammatory lesion was present in the chorionic plate. A significantly lower incidence of pre-eclampsia was found in the group with the lesion; 0% versus 45.5%. A significant relation was found between this lesion and the presence of intervillositis, chronic deciduitis, presence of plasma cells and fibrin deposition in the decidua. Fluorescent in situ hybridisation with X/Y-chromosome probes showed that the majority of cells present in the lesion are of maternal origin. The expression of the macrophage marker CD14+ and of the type 2 macrophage (M2) marker CD163+ was significantly higher in the lesion. The incidence of a fetal HLA-C2 genotype was significantly higher in cases with a lesion compared to the group without the lesion. In conclusion, a striking relationship was observed between the presence of a not previously described inflammatory lesion in the chorionic plate and the absence of pre-eclampsia in ED pregnancies. The lesion consists of mainly maternal cells with a higher expression of the macrophage marker CD14+ and the M2 marker CD163+. These findings suggest a protective immune mechanism which might contribute to the prevention of severe clinical complications like pre-eclampsia.

Selective advantage of HLA matching in successful uncomplicated oocyte donation pregnancies

“…Intriguingly, Schonkeren et al showed a significantly higher incidence of the fetal HLA-C2 genotype in pregnancies with a distinct lesion in the chorionic plate of uncomplicated OD pregnancies. This lesion was not observed in placentas from preeclamptic OD pregnancies and an immunological protective mechanism against the allogeneic fetus was suggested (Schonkeren et al, 2012). Indeed, in the group that showed this lesion the fetal C2 was more often combined with the protective maternal haplotype KIR B (Schonkeren et al, 2012).…”

“…This lesion was not observed in placentas from preeclamptic OD pregnancies and an immunological protective mechanism against the allogeneic fetus was suggested (Schonkeren et al, 2012). Indeed, in the group that showed this lesion the fetal C2 was more often combined with the protective maternal haplotype KIR B (Schonkeren et al, 2012). However, the number of patients was small and the frequency of KIR A/fetal C2 combination should be tested in preeclamptic OD pregnancies, regardless of the chorionic plate lesion, and in spontaneously aborted OD pregnancies.…”

A new era in reproductive medicine: consequences of third-party oocyte donation for maternal and fetal health

“…3) [63]. Interestingly, when inflammatory lesions are found in the chorionic plate in OD pregnancy, the incidence of preeclampsia is very low (0 %), while preeclampsia shows a very high incidence (45.5 %) when inflammation of the chorionic plate is not detected [63].…”

Gestational Diabetes and Maternogenic Preeclampsia: By-products of the Accelerated Metabolic Syndrome in Pregnancy

“…In ovodonated mothers, unique and typical immune-adaptive changes are found in successful pregnancies, but not in those developing preeclampsia [ 44 ].…”