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Oocyte donation (OD) is a high risk for preeclampsia because a fetus is a complete allograft to the maternal host. However the differences of immune status between preeclamptic OD cases and normotensive OD cases have not been clarified. Objective To clarify the immunological differences between preeclamptic OD cases and normotensive OD cases. Methods Deciduel CD3+Tcells, CD4+Tcells, CD8+Tcells, Foxp3+Treg cells CD56+NK cells and CD68+ macrophage were evaluated by immunohistochemistry. Peripheral blood effector Treg cells were evaluated by flow cytometry in 5 preeclamptic OD cases and 16 normotensive OD cases. Results The populations of CD3+ T cells, CD4+ T cells, CD8+ T cells, Foxp3+ Treg cells, CD56+ NK cells and CD68+ macrophage in placental bed biopsy samples of OD cases were significantly lower compare to those in normal pregnancy subjects. Those levels in preeclamptic OD cases were similar to those in normotensive OD cases. Same findings were observed in preeclamptic cases in natural conception. Vascular remodeling of spiral arteries was very poor in OD cases regardless of the presence of preeclampsia. These findings were quite similar to those in preeclampsia of natural conception. Peripheral blood-effector Treg cells was significantly decreased in preeclampsia, but these levels in OD pregnancies were not changed in preeclamptic OD cases and normotensive OD cases. Conclusion Poor vascular remodeling and some of the immunological changes were observed in uncomplicated OD pregnancy, but we have not yet identified the crucial factors that lead to preeclampsia in OD pregnancy.

Introduction The pathogenesis of preeclampsia remains largely unknown. However, many researches support the immune maladaptation hypothesis. Epidemiological findings show that first pregnancy, the use of barrier contraceptive method or short cohabitation, oocyte donation cases and obesity are the risks for preeclampsia. These factors seem to be independent. Objective We tried to explain the relationship between the epidemiological risks for preeclampsia and immune maladaptation. Method We have studied the immune system in preeclamptic cases and oocyte donation cases using flow cytometry and immunohistochemical examination. Results Human pregnancy represents a semiallograft to the maternal host, therefore tolerance system is required. In oocyte donation cases, all the MHC of the fetus are allograft to maternal host, therefore more strict tolerance system is needed. Nevertheless, our study showed the number of regulatory T (Treg) cells which induce tolerance were scare at fetomaternal interface. Moreover, macrophage, T cell and NK cells that play important roles for vascular remodeling were also scarce in placental bed biopsy samples. Importantly, vascular remodeling was inadequate in oocyte donation cases regardless of the presence or absence of preeclampsia. These findings suggest that macrophage, T cell and NK cells play an important role for vascular remodeling of spiral artery and poor placentation is present in oocyte donation pregnancy. We also showed that effector Treg cells decreased and exhausted Treg cells increased in peripheral blood of preeclampsia. Expression of Bcl-2 in Treg cells was decreased and expression of Bax in Treg cells was increased suggesting that Treg cells in preeclampsia are more likely to die by apoptosis. In our mice model, seminal plasma plays an important role for induction of paternal antigen specific Treg in the uterus. This finding explains barrier contraceptive method or short cohabitation are the risk of preeclampsia. We also showed the positive relationship between BMI and the frequencies of cytotoxic T cells and cytotoxic NK cells. Conclusion These findings support that immune maladaptation is one of the mechanisms of preeclampsia.

Objectives Allograft pregnancy such as oocyte donation and embryo donation has higher risks of placental complications including preeclampsia. Altered spiral arterial remodeling and the regional T, NK cells and monocyte population characteristics were studied in oocyte donation. Methods Decidua basalis were collected during scheduled cesarean sections from 19 women who conceived by oocyte donation (OD) and 18 women with normal gestation (CTR). Spiral arterial remodeling was studied using extra-villous trophoblastic (EVT) marker CK7 and vascular endothelium marker CD31 by immunohistochemistry. The regional T cell population was studied using CD3, CD8, Foxp3, and CD56 for T cells, cytotoxic T cells, regulatory T cells and NK cells, respectively. Macrophages were stained with CD68. The staining of P62 immunohistochemistry was also included to detect impaired response to oxidative stress by autophagy. The helper T cell count was estimated by subtracting CD8+ cells counts from CD3+ cells counts. Quantitation was done by counting immunopositive cells in 4 high power fields (×100). This study was reviewed and approved by the institutional review boards of Aiiku hospital and University of Toyama. Results When OD is compared to CTR, the vascular endothelium was incompletely replaced by EVT, indicating attenuated remodeling. The regional T cell analysis showed decreased CD3+ (8.83 vs 25.5: median), CD8+ (4.17 vs 12.0), CD4+ (4.63 vs 13.5), Foxp3+ (0.63 vs 2.00) CD56+ (4.00 vs 15.3) and CD68+ (6.25 vs 16.5). P62/CK7 ratio was four times higher in OD than CTR. Conclusions OD pregnancies have inappropriate remodeling of the spiral arteries and decreased regulatory T cell expression, macrophage, NK cells accumulation in the region. The characteristic difference coincided with a decreased autophagy, thus impaired response to oxidative stress. Our novel findings may at least in part be the etiology of the clinically well-known higher incidence of preeclampsia in the oocyte donation gestation. Disclosures Y. Nakabayashi: None. A. Nakashima: None. T. Shima: None. H. Sakamoto: None. T. Adachi: None. T. Okai: None. M. Nakabayashi: None. S. Saito: None.