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Citation Saito S, Nakashima A, Shima T, Ito M. Th1/Th2/Th17 and regulatory T‐cell paradigm in pregnancy. Am J Reprod Immunol 2010T‐helper (Th) cells play a central role in modulating immune responses. The Th1/Th2 paradigm has now developed into the new Th1/Th2/Th17 paradigm. In addition to effector cells, Th cells are regulated by regulatory T (Treg) cells. Their capacity to produce cytokines is suppressed by immunoregulatory cytokines such as transforming growth factor (TGF)‐β and interleukin (IL)‐10 or by cell‐to‐cell interaction. Here, we will review the immunological environment in normal pregnancy and complicated pregnancy, such as implantation failure, abortion, preterm labor, and preeclampsia from the viewpoint of the new Th1/Th2/Th17 and Treg paradigms.

The increasing use of nanomaterials has raised concerns about their potential risks to human health. Recent studies have shown that nanoparticles can cross the placenta barrier in pregnant mice and cause neurotoxicity in their offspring, but a more detailed understanding of the effects of nanoparticles on pregnant animals remains elusive. Here, we show that silica and titanium dioxide nanoparticles with diameters of 70 nm and 35 nm, respectively, can cause pregnancy complications when injected intravenously into pregnant mice. The silica and titanium dioxide nanoparticles were found in the placenta, fetal liver and fetal brain. Mice treated with these nanoparticles had smaller uteri and smaller fetuses than untreated controls. Fullerene molecules and larger (300 and 1,000 nm) silica particles did not induce these complications. These detrimental effects are linked to structural and functional abnormalities in the placenta on the maternal side, and are abolished when the surfaces of the silica nanoparticles are modified with carboxyl and amine groups.

These recommendations from the ISSHP are based upon available literature and expert opinion. It is intended that this be a 'living' document, to be updated when needed as more research becomes available to influence good clinical practice. Unfortunately there is a relative lack of high quality randomised trials in the field of Hypertension in Pregnancy compared with studies in essential hypertension outside of pregnancy and ISSHP encourages greater funding and uptake of collaborative research in this field. Accordingly, the quality of evidence for the recommendations in this document has not been graded, though relevant references and explanations are provided for each recommendation. The document will be a 'living' guideline and we hope to be able to grade recommendations in the future.Guidelines and recommendations for management of hypertension in pregnancy are typically written for implementation in an ideal setting. It is acknowledged that in many parts of the world, it will not be possible to adopt all of these recommendations; for this reason, options for management in less-resourced settings are discussed separately in relation to diagnosis, evaluation, and treatment. This document has been endorsed by the International Society of Obstetric Medicine (ISOM) and the Japanese Society for the Study of Hypertension in Pregnancy (JSSHP). 5 KEY POINTS: All units managing hypertensive pregnant women should maintain and review uniform departmental management protocols and conduct regular audits of maternal & fetal outcomes.The cause(s) of pre-eclampsia and the optimal clinical management of the hypertensive disorders of pregnancy remain uncertain; therefore, we recommend that every hypertensive pregnant woman be offered an opportunity to participate in research, clinical trials and follow-up studies. Classification1. Hypertension in pregnancy may be chronic (pre-dating pregnancy or diagnosed before 20 weeks of pregnancy) or de novo (either pre-eclampsia or gestational hypertension).2. Chronic hypertension is associated with adverse maternal and fetal outcomes and is best managed by tightly controlling maternal blood pressure (BP 110-140/85 mmHg), monitoring fetal growth and repeatedly assessing for the development of pre-eclampsia and maternal complications. This can be done in an outpatient setting.3. White-coat hypertension refers to elevated office/ clinic (≥140/90mmHg) blood pressure but normal blood pressure measured at home or work (<135/85mmHg); it is not an entirely benign condition and conveys an increased risk for pre-eclampsia. 6 4. Masked hypertension is another form of hypertension, more difficult to diagnose, characterised by blood pressure that is normal at a clinic or office visit but elevated at other times, most typically diagnosed by 24 hour ambulatory BP monitoring (ABPM) or automated home blood pressure monitoring (HBPM). 5.Gestational hypertension is hypertension arising de novo after 20 weeks' gestation in the absence of proteinuria and without biochemical or haematological abnormalities. It...

SUMMARYWe calculated the percentage of Th1, Th2, Th0 cells and the Th1:Th2 cell ratio of peripheral blood from normal pregnant subjects and preeclampsia patients using¯ow cytometry which can analyse both the surface marker, CD4, and intracellular cytokines, interleukin (IL)-4 and interferon (IFN)-g. In normal pregnancy, the percentage of Th1 cells was signi®cantly lower in the third trimester, and the ratios of Th1:Th2 were signi®cantly lower in the second and third trimester than in nonpregnant subjects. In contrast, the percentage of Th1 cells and the ratios of Th1:Th2 in preeclampsia were signi®cantly higher than in normal third trimester pregnant subjects. The percentage of Th2 cells in preeclampsia was signi®cantly lower than in third trimester of normal pregnancy. Additionally, peripheral blood mononuclear cells from these subjects and patients were cultured with phytohemagglutinin stimulation, and IL-4 and IFN-g concentrations were determined in the supernatant by enzymed linked immunosorbent assays. The percentage of Th1 and Th2, and the ratios of Th1:Th2 were correlated with cytokine (IFN-g and IL-4) secretion level. These results demonstrated that Th2 cells were predominant in the second and third trimesters of normal pregnancy, but Th1 cells predominated in preeclamptic patients.

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Summary CD4+ CD25 bright regulatory T (Treg) cells have been identified as a principle regulator of tolerance during pregnancy. In the setting of pre-eclampsia, however, little is known about the dynamics of these cells. In the current study, we determined CD4 + CD25 bright Treg cells in the peripheral blood using flow cytometry and forkhead box P3 (FoxP3 + ) cells at the placental bed using immunohistochemical staining. Peripheral blood mononuclear cells (PBMC) of 38 pre-eclamptic cases (17 cases Japanese, 21 cases Polish), 40 normal late pregnancy subjects (20 subjects Japanese, 20 subjects Polish), and 21 non-pregnant healthy controls (10 subjects Japanese, 11 subjects Polish) were included. We found the percentage of CD25 bright cells within the CD4+ T cell population in PBMC was reduced significantly in both Japanese and Polish pre-eclamptic cases than in normal pregnancy subjects (P < 0·001) and non-pregnant healthy controls (P < 0·001). Also, the percentage of FoxP3+ cells within CD3 + T cells in the placental bed biopsy samples of pre-eclamptic cases were decreased compared to those in normal pregnancy subjects. These findings suggest that a decreased number of Treg cells was present in pre-eclampsia, and these changes might break the maternal tolerance to the fetus.