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Pregnancy is a critical stimulator of bone mineral resorption. We used to find the MTHFR gene polymorphisms are related with blood lead levels among pregnant women. Pregnancy-stimulated bone turnover may be associated with MTHFR gene polymorphisms too. In this article, we aimed to determine the relationship between MTHFR gene polymorphisms and bone turnover rates among the pregnant women. The participants including pregnant and non-pregnant women were selected and recruited during their routine prenatal or physical examination from July to October in 2012. A total of 1000 participants, including 250 pregnant women in the first, second, and third trimesters and 250 non-pregnant women, were enrolled in the study. Finally, after excluding 27 participants unable to provide blood samples, 973 eligible participants (i.e., 234,249, and 248 pregnant women in the first, second, and third trimesters, respectively, and 242 non-pregnant women) were included in the research. The MTHFR gene 1298CC homozygote carriers were more susceptible to yield higher plasma homocysteine levels than the 1298AA/AC carriers, with standardized coefficients of 0.086 (P

BackgroundPregnancy is an important stimulus of bone lead release. Elevated blood lead levels (BLLs) may cause adverse pregnancy outcomes for mothers and harmful lead effects on fetuses. However, the reports about maternal BLL changes during pregnancy are conflicting to some extent. This article is to explore the variations in BLLs among pregnant women. The relationships of BLLs with methylenetetrahydrofolate reductase (MTHFR) gene C677T, A1298C, and G1793A polymorphisms, which are associated with bone resorption, were also studied. A total of 973 women, including 234, 249, and 248 women in their first, second, and third trimesters, respectively, and 242 non-pregnant women, were recruited at the Wuhan Women and Children Medical Health Center.MethodsBLLs were determined using a graphite furnace atomic absorption spectrometer. Single-nucleotide polymorphisms of MTHFR were identified with the TaqMan probe method.ResultsThe geometric mean (geometric standard deviation) of BLLs was 16.2 (1.78) μg/L for all participants. All the studied MTHFR alleles were in Hardy-Weinberg equilibrium. Multiple-linear regression analysis revealed the following results. Among the pregnant women, those that carried MTHFR 677CC (i.e. wild-genotype homozygote) and 1298CC (i.e. mutant-genotype homozygote) exhibited higher BLLs than those that carried 677CT/TT (standardized β = 0.074, P = 0.042) and 1298AC/AA (standardized β = 0.077, P = 0.035) when other covariates (e.g., age, no. of children, education and income, etc.) were adjusted. The BLLs of pregnant women consistently decreased during the pregnancy and these levels positively correlated with BMI (standard β = 0.086-0.096, PConclusionsThe 1298CC mutant-type homozygote in the MTHFR gene is a risk factor for high BLLs among low-level environmental lead-exposed Chinese pregnant women, whose BLLs consistently decreased during gestation.

To investigate the distribution of human leukocyte antigen (HLA)-G and E on human first trimester placenta and its relationship with unexplained recurrent spontaneous abortion (RSA).Fifteen women with normal first trimester pregnancy and fifteen patients with RSA were included in this study. In situ hybridization and immunohistochemical staining were employed to detect the mRNA and protein of HLA-G, E in first trimester placenta.The HLA-G, E mRNA were detected in all trophoblasts, including syncytiotrophoblast, villous and extravillous cytotrophoblast. HLA-G protein was only found at extravillous trophoblast by mAb 4H84 specific to HLA-G. The same expression sites were observed for both HLA- E protein and its mRNA. The expression of HLA-G, E mRNA in the RSA group were much lower than those in the control group. The HLA-G, E protein were also expressed at low level in RSA group.The inconsistency of the distribution of HLA-G mRNA and protein was probably due to the monoclone antibody 4H84. There is strong correlation between lack of the mRNA and protein expression of HLA-G, E found in the trophoblasts at the fetal-maternal interface and RSA.

To investigate the expression of human leucocyte antigen G (HLA-G) on human placenta and its gene polymorphism in relation to intrahepatic cholestasis of pregnancy (ICP).Immunohistochemistry was utilized to detect the HLA-G protein expression on third trimester placenta of fifteen normal pregnant women (control group 1), fifteen ICP patients treated with dexamethasone (ICP group with dexamethasone treatment) and ten ICP patients treated without dexamethasone (ICP group without dexamethasone treatment). We used polymerase chain reaction with sequence-specific primer (PCR-SSP) method to detect the 14 bp deletion polymorphism in exon 8 of HLA-G gene of thirty normal pregnant women and their babies (control group 2), thirty ICP patients and their babies (ICP group).(1) The positive expression of HLA-G on placenta extravillous cytotrophoblast and its mean optical density of ICP group without dexamethasone treatment 56 +/- 8 was significantly lower than those of normal control group 70 +/- 10 and ICP group with dexamethasone treatment 66 +/- 9 (P0.05). No significant differences were found between normal control group and ICP group with dexamethasone treatment (P0.05). (2) There were no statistical differences between the control group and the ICP group with regard to the allele and genotype of the 14 bp deletion polymorphism in exon 8 of HLA-G gene (P0.05).The reduced expression of HLA-G on placenta in ICP patients may alter the maternal-fetal immune response and thus be involved in the pathogenesis of this disorder. Dexamethasone can upregulate the expression of HLA-G on placenta. The 14 bp deletion polymorphism in exon 8 of HLA-G gene might not have a significant influence on the development of ICP.

To study the clinical features and diagnosis of intrahepatic cholestasis of pregnancy (ICP).During the last 10 years 1241 cases of ICP stayed in our hospital. Their clinical data were retrospectively reviewed.5.2% of all the maternity patients had ICP. It occurred more in winter and 3.5% of ICP occurred in multiple pregnancies. The recurrence rate of ICP was 30.2%. On the average, it occurred at gestational week 32.6. Skin pruritus was the characteristic manifestation and the presenting symptom in 1201 patients (96.8%). The other presenting features included elevated serum ALT and AST (2.3%), jaundice (8 patients), diarrhea (3 patients), deep yellow urine (2 patients) and right upper abdominal pain (1 patient). The serum transaminases levels were elevated, of which 60% were between 50-200 IU/L. Serum total bile acid (TBA) levels were elevated in 82.4% of the patients and bilirubin levels in 33.4%. The elevated bilirubin levels were 30 to 90 micromol/L in 85% of those patients with this condition, and it was never higher than 170 micromol/L.The basic diagnostic points of ICP are pruritus and abnormal liver function characterized by increased transaminases and TBA. Therefore paying attention to typical pruritus and other atypical features such as elevated serum transaminases, jaundice, diarrhea, deep yellow urine and right upper abdominal pain during antenatal care is important for an early diagnosis of ICP.

To investigate the expression of corticotropin-releasing hormone and its receptor type-1 in human placental tissues during caesarian operations.IHC-SP staining and ISH methods were adopted to identify the expression patterns of CRH and its receptor CRH-R1 in the placenta taken from the women who had uncomplicated pregnancies. The placental tissues were collected after caesarian operations on the women with threatened labor.Positive expressions of both CRH and CRH-R1 messenger ribonucleic acid and peptide were found in the placental tissues, but the later was stronger (P0.05).The elevated level of placental CRH may be a trigger of the transcription of its own receptor CRH-R1 during caesarian operations. This positive feedback of CRH on its own receptor may represent a functional adaptation of human utero-plcental-fetal unit in responding to stress.

To explore effect of fetal lymphocyte on pathogenesis of intrahepatic cholestasis of pregnancy (ICP).Twenty pregnant women with ICP and 20 normal pregnant women were enrolled in the study. The single mixed lymphocyte culture/reaction (MLC/MLR) was conducted using inactive lymphocyte obtained from maternal peripheral blood and lymphocyte of cord blood from fetus. Antigen-induced-lymphocyte-proliferation-reaction was used for dermic soluble antigen and decidual soluble antigen obtained from maternal blood and cord blood from fetus. The intense of proliferation was calculated and compared between normal and ICP-complicated pregnancies.(1) The level of intense of proliferation of fetal lymphocyte was significantly increased in ICP group 2.75 +/- 0.36 than those of normal control group 1.45 +/- 0.19 in single mixed lymphocyte culture (P0.05). (2) The level of intense of proliferation of fetal lymphocyte was significantly increased in ICP group 1.45 +/- 0.19 than those of normal control group 0.67 +/- 0.24 in decidual soluble antigen induced lymphocyte proliferation reaction (P0.05). (3) The level of intense of proliferation of fetal lymphocyte was significantly increased in ICP group (1.22 +/- 0.44) than those of normal control group (0.66 +/- 0.27) in dermic soluble antigen induced lymphocyte proliferation reaction.(1) The fetal lymphocyte may be one of the effector cells in pathogenesis of ICP. (2) The disturbance of fatal-maternal immune-tolerance is one of the important mechanisms underlying ICP.

To investigate the kinds of ERa, ERbeta mRNA and the localization of ERa, ERbeta on normal human placenta.The expression and localization of ERa,ERbeta on normal human placenta were detected by reverse transcription-ploymerase chain reaction (RT-PCR) and immunhistochemistry (SP-assay).There was mRNA expression of ERalpha and ERbeta on human term placenta, and ERbeta was identified with ERbeta5. The ERa immunoreactivity on human term placenta was in villous cytotrophoblastic nucleus, and that of ERbeta was in syncytiotrophoblastic cytoplasm.The findings indicate that ERbeta5 is the kind of ERbeta on placenta. It is localizated in the cytoplasm of syncytiotrophoblast and is probably connected with the production of estrogen.

To explore the relationship between human leukocyte antigen-DQA1 (HLA-DQA1) allele gene polymorphism and intrahepatic cholestasis of pregnancy (ICP).Forty-five patients with ICP, eighteen ICP families, forty-five normal pregnant women and eighteen normal control families were tested for HLA-DQA1 allele gene polymorphism by polymerase chain reaction with sequence-specific primer (PCR-SSP) method.The frequency of HLA-DQA1*0301 in normal pregnant women was markedly higher than that in the ICP group (P0.05). No significant differences were observed between the frequencies of other detected HLA-DQA1 alleles in both groups. The analysis of feto-maternal or couples sharing of the HLA-DQA1 alleles showed that no significant differences were observed between the two groups.The above findings suggest that there is no significant association between the genetic polymorphisms in HLA-DQA1 and ICP in Chengdu district; HLA-DQA1*0301 may be a protective gene against ICP. It may prevent the development of ICP.

To investigate the expression pattern of vascular cell adhesion molecule-1(VCAM-1) and endothelial selectin (E-selectin) in the placental bed extravillous cytotrophoblast (EVCT) as well as its relationship with preeclampsia.Placentas from severe preeclampsia (n=20) and gestional age-matched normal pregnancies (n=20) were studied. The staining intensity and the Mean Optical Density (MOD) of VCAM-1 and E-selectin in EVCT of placental bed deciduas were measured by immunohistochemistry.The staining intensity and MOD of VCAM-1 and E-selectin on placental bed EVCT in severe preeclampsia were significantly lower than those in the control group respectively (P0.05, P0.01).The decreased EVCT expression of vascular adhesion phenotype VCAM-1 and E-selectin may account for the shallow trophoblast invasion in preeclampsia, which is the major pathological change of this disease.

To study the expression of corticotropin-releasing hormone(CRH) and its receptor type-1 in the placental cotyledon vessels at term.IHC-SP staining and ISH methods were used to investigate the expression patterns of CRH and its receptor CRH-R1 in the placental cotyledon vessels at term from women who had undergone uncomplicated pregnancies. Placental tissues were collected after cesarian section before threatened labor.This study revealed for the first time that endothelial cells and even smooth muscle cells of the cotyledon vessel expressed CRH messenger ribonucleic acid and peptide as well as the CRH-R1.The novel findings disclosed that the CRH derived from endothelial cells and even smooth muscle cells of the cotyledon vessel may represent the main source of CRH levels in fetal plasma, thus indicating the capability of mobilizing the compensation mechanism for adapting to the acute stress.

To investigate the influence of transforming growth factor-beta2 (TGF-beta2) on production of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) from placenta of patients with intrahepatic cholestasis of pregnancy (ICP).Villous explants from 10 ICP patients (ICP group) and 10 normal gravidae (control group) were cultured in vitro. The concentrations of TNF-alpha and IFN-gamma in the culture medium were determined by enzyme linked immunoadsorbent assay (ELISA) after incubation with different concentrations of TGF-beta2 for 1, 24 and 48 hours.(1) After cultured for 1, 24 and 48 hours, TNF-alpha level in ICP group was (771 +/- 187) pg/g, (2 490 +/- 575) pg/g, and (3339 +/- 1106) pg/g, respectively, while IFN-gamma level was (931 +/- 148) pg/g, (1888 +/- 545) pg/g, and (3027 +/- 667) pg/g, respectively. All were significantly higher than those in the normal group (P0.001). (2) TGF-beta2 could inhibit the release of above cytokines in a time- and dose-dependent manner: TNF-alpha level was (2490 +/- 575) pg/g, (1806 +/- 502) pg/g, and (1231 +/- 238) pg/g after 24 h, (3339 +/- 1106) pg/g, (2168 +/- 794) pg/g, and (1047 +/- 183) pg/g after 48 h, respectively; IFN-gamma level was (1888 +/- 545) pg/g, (1 347 +/- 405) pg/g, and (913 +/- 303) pg/g after 24 h, and (3027 +/- 667) pg/g, (2062 +/- 795) pg/g, and (1001 +/- 301) pg/g after 48 h, respectively.(1) The excessive production of TH1 type cytokines TNF-alpha and IFN-gamma may involve in the pathogenesis of ICP; (2) TGF-beta2 may exert immunoprotection effect through inhibiting the production of TNF-alpha and IFN-gamma.

To investigate the clinical characteristics of intrahepatic cholestasis of pregnancy (ICP).Totally 1241 cases of ICP during the 10 years from Jan 1991 to Dec 2000 in our hospital were retrospectively reviewed.Forty-four (3.5%) patients were multiple gestation. One hundred and one (8.1%) patients had pregnancy induced hypertension. ICP recurred in 30.2% multipara (38/126). On average, it occurred at gestational week of 32.6. Pruritus was the first symptom in 1201 (96.8%) patients while 8 (0.6%) patients had jaundice and 28 (2.3%) patients had abnormal liver function at the onset. Serum total bile acid (TBA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were usually mild or moderately elevated, while some patients had normal TBA (17.7%), ALT (15.6%), or AST (17.1%) level. The albumin/globulin ratio was reversed in 35 (3.2%) patients.ICP tends to recur in subsequent pregnancy. It is more likely to develop in multiple gestation. Pruritus is the most common and prominent manifestation. Elevated TBA and ALT or AST level is helpful for diagnosis. It should be noted that the above manifestations might not be typical in some patients.