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CD1d is a specific ligand for the invariant Valpha24Vbeta11-natural killer T (iNKT) cells that play an important role in placental development during early human pregnancy. The localization and regulation of placental CD1d expression remain unclear. Immunohistochemistry of human early gestational placentas revealed CD1d was present in villous and extravillous trophoblast (EVT) but not in syncytiotrophoblast or decidual cells. CD1d immunoreactivity in EVT cells decreased with EVT differentiation. Flow cytometry of primary cultured human trophoblast cells confirmed cell-surface expression of CD1d decreased with time in culture. These changes in CD1d expression occur at the level of transcription. TGF-beta1 secreted from the cultured EVT cells accumulated with time in culture and directly suppressed CD1d expression, as evidenced by monoclonal antibody neutralization of TGF-beta1 effects. Thus, trophoblast differentiation is characterized by TGF-beta1-mediated decreases in trophoblast cell CD1d expression. This effect may support appropriate activation of decidual iNKT cells at the maternal-fetal interface.

Aim Preoperative autologous blood donation ( PAD) has the advantages over allogeneic blood transfusion of theoretically no risk of viral infection and alloimmunization. However, there are some concerns regarding PAD in pregnant women, as they sometimes become anemic and adverse effects such as low blood pressure could be harmful to fetuses. In our hospital, the PAD program was implemented in 2006 and has been used in pregnant women at high risk of massive hemorrhage. In this study, the safety of PAD in pregnant women and its efficacy for avoiding allogeneic blood transfusion were investigated. Methods The hospital records of pregnant women who delivered at our hospital from January 2009 to June 2012 were reviewed and those who were enrolled in the PAD program for predicted massive hemorrhage were analyzed. Results Among the total of 3095 deliveries, 69 cases enrolled in the PAD program were analyzed. Blood donation was performed 189 times for the 69 cases. The median donated blood volume was 1200 m L (range, 400-2000). The mean blood loss during delivery was 1976 ± 1654 m L. Autologous blood was transfused in 64 cases. Allogeneic blood transfusion was required in five cases of massive blood loss exceeding 5000 m L. In the other 64 cases, no additional allogeneic blood transfusion was required. No adverse events were observed in either the pregnant women or fetuses. Conclusion For pregnant women at a high risk of massive hemorrhage, our PAD program was safe and effective for avoiding allogeneic blood transfusion. [ABSTRACT FROM AUTHOR]

Clinical outcome of confined placental mosaicism ( CPM) is varied, from normal pregnancy to intrauterine fetal death. It has been suggested that CPM for trisomy 2 is less likely to cause serious adverse effect on pregnancy. We hereby report a case of CPM for trisomy 2, which presented severe fetal growth restriction ( FGR) and placental abnormalities. A 30-year-old woman was referred to our hospital at 17+2 weeks because of marked FGR. Ultrasonography demonstrated prominent placental hypertrophy with multiple focal defects without any fetal structural abnormalities. Amniocentesis at 18+3 weeks revealed normal karyotype. Fetal growth rate worsened with gestational weeks, reaching −7 standard deviation at 36 weeks. At 37 weeks, the fetal condition suddenly deteriorated, ending in a stillbirth of a 756-g female baby. Postnatal cytogenetic analysis by array comparative genomic hybridization revealed trisomy 2 of the chorionic villi, and CPM for trisomy 2 was suggested as the cause of FGR and placental abnormalities. [ABSTRACT FROM AUTHOR]

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a cardiac disease that affects the right side of the heart and causes ventricular arrhythmias. It is considered as the most common cause of sudden cardiac death in young adults. However, risk and optimal management of ARVC during pregnancy and delivery remain unclear due to the small number of reported cases. Here we report a case of successful management of pregnancy and delivery in a patient with ARVC, who had a history of sustained ventricular tachycardia from her previous pregnancy. [ABSTRACT FROM AUTHOR]

Citation Iwasawa Y, Kawana K, Fujii T, Schust DJ, Nagamatsu T, Kawana Y, Sayama S, Miura S, Matsumoto J, Adachi K, Hyodo H, Yamashita T, Kozuma S, Taketani Y. A possible coagulation-independent mechanism for pregnancy loss involving β2glycoprotein 1-dependent antiphospholipid antibodies and CD1d. Am J Reprod Immunol 2012; 67: 54-65 Problem β2glycoprotein1 (β2GP1)-dependent antiphospholipid antibodies (aPL) increase the risk for recurrent pregnancy loss. We address whether anti-β2GP1 antibodies can interact with phosphatidylserine (PS)-bearing CD1d on trophoblast cells and induce local inflammation. Methods CD1d-bearing choriocarcinoma cells were used in flow cytometry and immunoprecipitation experiments. CD1d-mediated cytokine induction was assessed using antibody cross-linking. Cytokine production during co-culture of decidual lymphocytes with CD1d-bearing cells was also examined. Results Trophoblast surface-expressed CD1d forms a complex with PS-bound β2GP1. Anti-β2GP1 mAb cross-linking causes IL12p70 release from CD1d-bearing cells. IL12p70 release from CD1d-bearing trophoblast cells was also induced during co-culture with human decidual lymphocytes. The addition of anti-β2GP1 mAb to co-cultures resulted in a three-fold increase in IL12p70 secretion. IFNγ secretion from decidual lymphocytes was also induced during co-culture with anti-β2GP1 mAbs. Conclusions β2GP1-dependent IL12 release from CD1d-bearing trophoblast in the presence of aPL may link the antiphospholipid syndrome to pregnancy loss via an inflammatory mechanism. [ABSTRACT FROM AUTHOR]

Problem Lysophosphatidic acid (LPA) is a bioactive lipid mediator and thought to play an important role in pregnancy. Plasma LPA is produced by autotaxin (ATX), and ATX activity in plasma increases during pregnancy paralleled with gestational weeks and decreases to near the non-pregnant level soon after delivery. However, the source of increased ATX during pregnancy is still uncertain. We hypothesized that the source of increased ATX might be placenta. Method of study We investigated the protein and mRNA expression of ATX in human placenta using immunohistochemistry and RT-PCR, respectively. Results At all 3 gestational trimesters, immunohistochemical staining for placenta tissues revealed the most marked positive staining of ATX protein in trophoblasts. Real-time PCR revealed that mRNA amounts of ATX in placenta tissues paralleled with gestational weeks, i.e. ATX level in plasma. Conclusion These findings suggest that trophoblasts might produce ATX and its bioactive resultant substance, LPA, paralleled with gestational weeks. [ABSTRACT FROM AUTHOR]

Abstract: In human pregnancy, CD14+ decidual macrophages (DMs) are the dominant professional antigen-presenting cells in the decidua, comprising 20–30% of the local leukocyte population. Although the relevance of DMs to feto-maternal immune tolerance has been described, the molecular mechanisms underlying these functions have not been fully elucidated. B7-H1, a costimulatory ligand in the B7 family, negatively modulates T cell activity by binding to its corresponding receptor, PD-1. The present study aimed to investigate the functional significance of costimulatory interactions between DMs and T cells, with a particular focus on B7-H1:PD-1 signaling. An analysis of the expression profile of B7 ligands on human DMs revealed that B7-H1 was present on DMs isolated from early but not term pregnancies. B7-H1 was not expressed on the peripheral monocytes (PMs) of pregnant women. In response to IFN-γ, B7-H1 expression was induced on PMs and was enhanced on DMs, suggesting that this cytokine might be a key factor in the control of B7-H1 expression in the decidua. The majority of decidual T cells were noted to exhibit robust expression of PD-1, whereas the expression was limited to a small subpopulation of circulating T cells. Functional assays demonstrated that DMs are able to suppress T cell IFN-γ production via B7-H1:PD-1 interactions. This suppressive property was not observed for PMs, which lack B7-H1. B7-H1 on DMs may function as a key regulator of local IFN-γ production and thereby contribute to the development of appropriate maternal immune responses to the fetus in early pregnancy. [Copyright &y& Elsevier]

Abstract: Background: The bioactive lipid lysophosphatidic acid (LPA) exerts multiple effects in the female reproductive system. Serum/plasma LPA is mainly produced by the lysophospholipase D activity of autotaxin (ATX). Previous studies have suggested that ATX has critical roles in cancer, reproduction, and vascular development. In the present study, we evaluated the usefulness of serum ATX measurements in pregnant women. Methods: We measured the serum ATX antigen levels in 32 normal pregnant women, 15 patients with pregnancy-induced hypertension (PIH), and 7 patients with preterm delivery using a recently developed automated enzyme immunoassay. Results: The serum ATX antigen levels in normal pregnant women were significantly higher than those in non-pregnant women (P <0.001). The serum ATX antigen levels in normal pregnant women were significantly and positively correlated with the gestational week (r=0.809, P <0.001). During the third trimester, the serum ATX antigen levels of the patients with PIH (3.299±1.720mg/l) were significantly lower than those of the normal pregnant women (4.915±2.323mg/l) (P =0.04). Conclusions: The serum ATX antigen level increases with the progression of pregnancy. The serum ATX level may be a serological marker for the prediction of PIH. [Copyright &y& Elsevier]

Abstract: Objective: Our objective was to examine whether heart rate time series of healthy normal fetuses possess fractal properties and, if so, to determine whether consistent changes in fractal features according to gestational age exist. Design of the study: One hundred nineteen fetal heart rate (FHR) recordings in 55 singleton pregnancies between the 22nd and 41st weeks were analyzed. Fractal analysis developed by Higuchi was performed. Changes of fractal dimension were examined according to gestational age. Results: Two characteristic scaling regions were present in each FHR trace. The fractal dimension defined within 500 ms to 5 s (D S; median 1.396, range 1.273–1.642) was lower than that defined longer than 30 s (D L; median 1.933, range 1.492–2.049) in every case. These two values were significantly different (p &#60;0.001). There was a statistically significant difference in the values of D S between (22–29 weeks, mean 1.323), (30–33 weeks, mean 1.443) (p =0.004), (34–35 weeks, mean 1.418) (p =0.002), (36 weeks, mean 1.409) (p =0.030), (37–38 weeks, mean 1.394) (p =0.006), and (40–41 weeks, mean 1.452) (p =0.001), respectively. D S values between (40–41 weeks), (37–38 weeks) (p =0.012), and (39 weeks, mean 1.369) (p =0.030), respectively, were also significantly different. The values of D L decreased from 22–39 weeks (median 1.941) to 40–41 weeks (median 1.891) (p =0.008). Conclusions: Two distinct fractal structures within the FHR variation were identified. Fractal features of heart rate of healthy normal fetuses change significantly during pregnancy period. Fractal analysis may be useful for evaluating FHR variation. [Copyright &y& Elsevier]