Maternal vitamin B1 is a determinant for the fate of primordial follicle formation in offspring.

The mediation of maternal-embryonic cross-talk via nutrition and metabolism impacts greatly on offspring health. However, the underlying key interfaces remain elusive. Here, we determined that maternal high-fat diet during pregnancy in mice impaired preservation of the ovarian primordial follicle pool in female offspring, which was concomitant with mitochondrial dysfunction of germ cells. Furthermore, this occurred through a reduction in maternal gut microbiota-related vitamin B1 while the defects were restored via vitamin B1 supplementation. Intriguingly, vitamin B1 promoted acetyl-CoA metabolism in offspring ovaries, contributing to histone acetylation and chromatin accessibility at the promoters of cell cycle-related genes, enhancement of mitochondrial function, and improvement of granulosa cell proliferation. In humans, vitamin B1 is downregulated in the serum of women with gestational diabetes mellitus. In this work, these findings uncover the role of the non-gamete transmission of maternal high-fat diet in influencing offspring oogenic fate. Vitamin B1 could be a promising therapeutic approach for protecting offspring health.

Pertinence between risk of preeclampsia and the renin-angiotensin-aldosterone system (RAAS) gene polymorphisms: an updated meta-analysis based on 73 studies.

The aetiological mechanism of preeclampsia (PE) is unclear exactly, so we attempted to investigate the association between susceptibility to preeclampsia and renin-angiotensin-aldosterone system (RAAS) gene polymorphisms to explore the aetiology in terms of genetics. A systematic search was performed in electronic databases to identify relevant studies. Eventually 73 studies were enrolled, odds ratios were generated by 5 genetic models. In overall analysis, significant associations were detected for AGT M235T, AT1R A1166C and CYP11B2 C344T whereas negative correlation was shown for AGT T174M. As stratified by race and geography, AGT 235T allele and AT1R 1166C allele increased preeclampsia risk and AGT T174M was justified uncorrelated with preeclampsia. Our meta-analysis illustrated that AGT 235T allele and AT1R 1166C allele increased and CYP11B2 344T allele decreased preeclampsia risk while AGT T174M polymorphism did not change preeclampsia risk. Hence, pregnant women carrying high-risk genotypes need strengthened management to prevent and early identification of preeclampsia.

Generation of a human iPSC line CIBi008-A from amniotic fluid-derived cells of a fetus with ß-thalassemia carrying variants of -28A > G and IVS-II-654C > T in HBB.

ß-thalassemia is mostly caused by homozygous or compound heterozygous variants in HBB. We generated a human iPSC line CIBi008-A from amniotic fluid-derived cells of a fetus with ß-thalassemia major, carrying compound heterozygous -28A > G and IVS-II-654C > T variants in HBB gene. This line will be a valuable resource for disease modeling and testing gene therapies for ß-thalassemia.

Correction to: Serum fatty acid-binding protein 4 (FABP4) as a novel biomarker to predict gestational diabetes mellitus.

The title "Plasma fatty acid-binding protein 4 (FABP4) as a novel biomarker to predict gestational diabetes mellitus" should be replaced by "Serum fatty acid-binding protein 4 (FABP4) as a novel biomarker to predict gestational diabetes mellitus".

Expression and role of microRNA 18b and hypoxia inducible factor-1α in placental tissues of preeclampsia patients.

Abnormal expression of hypoxia inducible factor-1α (HIF-1α) is closely associated with various diseases. By detecting the mRNA and protein expression levels of microRNA 18b (miR-18b) and HIF-1α in placental tissues of preeclampsia (PE) patients and studying the effects of miR-18b on total cellular metabolic activity, migration and invasion in normal human trophoblast cell lines (HTR-8/SVneo), the present study aimed to investigate the effect of miR-18b on targeted regulation of HIF-1α and its clinical significance in the development of PE. Expression levels of miR-18b and HIF-1α mRNA in PE placental tissues were detected by reverse transcription-quantitative polymerase chain reaction and corresponding expression levels of HIF-1α protein were analyzed by western blotting. miR-18b overexpression and inhibited miR-18b expression in HTR-8/SVneo cells, which were constructed by transfecting miR-18b mimic and inhibitor, respectively, were investigated and the total cellular metabolic activity, migration and invasion abilities in different groups of cells were compared. Expression levels of miR-18b were significantly reduced in PE placental tissues and miR-18b inhibitor-transfected HTR-8/SVneo cells, whereas the expression levels of HIF-1α were significantly increased in PE placental tissues and significantly decreased in miR-18b mimic-transfected HTR-8/SVneo cells. Overexpression of miR-18b inhibited the expression of HIF-1α and reduced the cell invasion, migration and viability of HTR-8/SVneo cells. However, inhibition of miR-18b expression promoted the expression of HIF-1α and increased the cell invasion, migration and total cellular metabolic activity of HTR-8/SVneo cells. The present study indicated that abnormal expression of HIF-1α exhibited in PE placental tissues was regulated by miR-18b. Furthermore miR-18b expression was demonstrated to affect cell invasion, migration and viability through target regulation of HIF-1α. The results of the present study suggest that miR-18b and HIF-1α may have important roles in the development of PE.

Zinc protection in fetal rats for maternal mercury exposure-induced growth retardation is probably associated with S100B expression.

AIM: The study was conducted to investigate the effects of maternal mercury exposure on fetal rat development and zinc protection in mercury-exposed rats. METHODS: Pregnant rats were subjected to zinc sulfate pre-feeding, mercury exposure and zinc sulfate co-feeding. The control rats were administered distilled water. On day 19, the placental weight, overall weight, size and tail length of fetal rats, mercury content and S100B level in the placenta were determined using Western blot analysis. RESULTS: Compared with the control, mercury exposure at 2.0 mg/kg.d significantly reduced placental weight and fetal development, resulting in reduced fetal weight, size and tail length, while zinc pre-feeding increased placental weight and other fetal developmental parameters. Compared with mercury exposure, co-feeding with zinc significantly reduced mercury-induced injury in the fetal rats. S100B and mercury content levels were significantly elevated in rats maternally exposed to methylmercury chloride, compared with the unexposed control, while co-feeding with methylmercury chloride and zinc sulfate significantly reduced S100B and mercury levels in the placenta. CONCLUSION: Maternal exposure to mercury results in increased S100B in the placenta. Zinc sulfate feeding could reduce S100B and mercury levels, thereby protecting the rats from mercury damage. S100B level may be used to measure the antagonism between zinc and mercury during pregnancy.

Plasma fatty acid-binding protein 4 (FABP4) as a novel biomarker to predict gestational diabetes mellitus.

AIMS: Fatty acid-binding protein 4 (FABP4) is mainly expressed in adipocytes and macrophages and is demonstrated to be elevated in diabetes patients. The aim of this study was to evaluate the possible role of FABP4 in the diagnosis of GDM and to investigate the relationship between FABP4 and overweight, insulin resistance and inflammatory marker TNF-α. METHODS: A total of 46 women with GDM and 55 age-matched pregnant women without GDM (non-GDM) were eligible for the study. Demographic and biochemical parameters and fasting venous blood samples of two groups were collected from all cases. Serum concentrations of FABP4 were determined using enzyme-linked immunosorbent assay (ELISA). The predictive value of Serum FABP4 level was evaluated using receiver operating characteristic curve (ROC curve) analysis. RESULTS: We found that the serum FABP4 levels were significantly higher in GDM compared to the non-GDM group. The area under the ROC curve assay yielded a satisfactory result of 0.94 (95 % confidence interval 0.90-0.98; p < 0.001). The best compromise between 86.96 % specificity and 89.09 % sensitivity was obtained with a cutoff value of 1.96 ng/mL for GDM diagnosis. Moreover, a significant positive correlation was observed between FABP4 and overweight, insulin resistance and TNF-α in pregnant women with GDM. CONCLUSIONS: These results suggest that serum FABP4 may potentially serve as a novel biomarker for the prediction of GDM.

[Expression of glucose regulated protein 78 and the pathogenesis of gestational diabetes mellitus].

OBJECTIVE: To investigate the relationship between the expression of glucose regulated protein 78 (GRP78) in the placental trophoblast cells and the pathogenesis of gestational diabetes mellitus (GDM). METHODS: All the patients were recruited from Qingdao Municipal Hospital from May 2013 to May 2014. Among them, fifty women with GDM were assigned to the GDM group, and fifty healthy women were defined as the control group. All of them received cesarean section because of breech presentation, contracted pelvis, scarred uterus or on mother's demand. Real-time PCR was conducted to analyze the expression of GRP78 mRNA in the trophoblasts. Immunohistochemistry was performed to detect the localization of GRP78 protein in the placentasl trophoblast cells. RESULTS: (1) GRP78 mRNA expressed in the cytoplasm of trophoblasts of both the GDM group and the control group. The GRP78 mRNA levels in the GDM group and the control group were 15.6±0.4 and 6.0±0.7, respectively. The relative expression level of GRP78 mRNA in the GDM group was 2.6 times of that in the control group, with statistically significant difference (P<0.01). (2) The expression of GRP78 protein was found in the cytoplasm of the trophoblasts of the GDM group. It showed in deep, light brown or yellow after staining, according to the expression degree. The expression of GRP78 protein was also found in the cytoplasm of the trophoblasts of the control group, but it mainly showed yellow color (38/50). The strong positive rate of GRP78 protein in the GDM group (96%, 48/50) was higher than that in the control group (22%, 11/50; P<0.01). CONCLUSION: The expression of GRP78 increased in the placental trophoblast cells of GDM patients. It might suggest that GRP78 had some effect on the pathogenesis of GDM.

[Relationship of S100B protein expression and the pathogenesis of early-onset and late-onset preeclampsia].

OBJECTIVE: To investigate the relationship of S100B protein expression and the pathogenesis of early-onset and late-onset preeclampsia. METHODS: Sixty patients with preeclampsia who received caesarean section at Qingdao Municipal Hospital from October 2010 to September 2011 were enrolled in this study. Thirty cases were early-onset preeclampsia (referred as early-onset preeclampsia group, < 34 weeks), and the other 30 cases were late-onset preeclampsia (referred as late-onset preeclampsia group, ≥ 34 weeks). Thirty women who received caesarean section because of pelvic structural deformities, breech presentation, macrosomia and social factors were included as the control group. The expression of S100B mRNA in the placenta was detected by reverse transcription (RT)-PCR. The expression of S100B protein in the placenta was detected by immunohistochemistry. RESULTS: (1) S100B mRNA was expressed in the trophoblasts of preeclampsia and control groups. The expression of S100B mRNA in early-onset preeclampsia group (0.73 ± 0.11) was significantly higher than the control group (0.58 ± 0.08) and late-onset preeclampsia group (0.64 ± 0.10, P < 0.05). There was no significant difference between late-onset preeclampsia group and the control group (P > 0.05). (2) S100B protein was expressed in the plasma membrane and cytoplasm of the trophoblasts, correlated positively with the brownish yellow and brown particles inside the cells. It was expressed in all the three groups. Immunohistochemistry revealed that the expression of S100B protein in the placenta of early-onset preeclampsia group was 100% (30/30), significantly higher than those of late-onset preeclampsia group and the control group, in which the positive rate were 70% (21/30) and 63% (19/30) respectively (P < 0.05). There was no difference between late-onset preeclampsia group and the control group (P > 0.05). CONCLUSION: Early-onset and late-onset preeclampsia may have different etiology and pathogenesis. S100B may be a factor in the pathogenesis of early-onset preeclampsia.

[Effects of transient receptor potential V6 silence on proliferation and apoptosis of trophoblasts].

OBJECTIVE: To investigate the effects of the transient receptor potential V6 (TRPV6) gene silencing on the proliferation and apoptosis of trophoblasts HTR-8/SVneo cells. METHODS: siRNA sequences targeting the TRPV6 gene were constructed and then transfected into HTR-8/SVneo cells mediated by liposome. The cells were divided three groups, including blank control (add the reagent of transfenction), negative control groups (transfecting nonspecific siRNA) and experimental groups (transfecting TRPV6-siRNA). Those cells in every group were collected at 24, 48, 72 hours after transfecting. The expression levels of TRPV6 mRNA were detected by reverse transcription (RT) PCR at different times after transfecting. The effects of siRNA on the proliferation and apoptosis of the cells were assayed by methyl thiagolyl tetragolium (MTT) and flow cytometry at different times after transfecting. RESULTS: siRNA TRPV6 transfection could inhibit the expression of TRPV6 mRNA in the HTR-8/SVneo cells. The expression was decreased with the extension of time, by 0.72 ± 0.02, 0.54 ± 0.02 and 0.29 ± 0.01 after 12, 48 and 72 hours of siRNA transfection as compared with the blank control and the negative control groups (P < 0.01). The rates of proliferation inhibition were (19.29 ± 1.23)%, (32.12 ± 1.35)% and (46.51 ± 1.42)% at 24, 48 and 72 hours respectively when compared with the blank control (2.12 ± 0.03)%, (2.42 ± 0.02)%, (3.13 ± 0.04)% and the negative control groups (2.37 ± 0.01)%, (2.61 ± 0.05)%, (2.93 ± 0.03)% (P < 0.01). The apoptosis rates of HTR-8/SVneo cells was 16.21% at 48 hours after transfected with siRNA TRPV6, which were significantly higher than 3.27% in the blank control and 5.34% in the negative control groups (P < 0.05). CONCLUSION: Silenceing of TRPV6 genen could inhibit the proliferation and increase the apoptosis of extravillous trophoblas of human placenta.

Altered expression of claudin-3 and claudin-4 in ectopic endometrium of women with endometriosis.

OBJECTIVE: To investigate the expression of claudin-3 and claudin-4 in the eutopic and ectopic endometrium of women with endometriosis and to evaluate the role of claudin-3 and claudin-4 in the pathogenesis of endometriosis. DESIGN: Cross-sectional measurement of gene expression levels of claudin-3 and claudin-4 on endometriotic tissue. SETTING: Academic. PATIENT(S): Thirty-five patients with endometriosis and 35 healthy women who were free of endometriosis were recruited for the study. INTERVENTION(S): Expression of claudin-3 and claudin-4 were investigated with immunohistochemical analysis, Western blot, and real-time polymerase chain reaction. Morphologic change of tight junction was also observed in different kinds of endometria. MAIN OUTCOME MEASURE(S): The expression levels of claudin-3 and claudin-4 in epithelial cells from 35 ectopic endometrial tissues, 27 eutopic endometrial tissues from women with endometriosis, and 35 normal endometrial tissues from women without endometriosis. RESULT(S): Expression of claudin-3 and claudin-4 was significantly lower in the ectopic endometriotic tissue than in the eutopic endometrium from women with endometriosis and normal controls at both the messenger RNA and protein levels. No significant difference was found between eutopic endometrium from women with endometriosis and normal endometrium from women without endometriosis. CONCLUSION(S): Down-regulated expression of claudin-3 and claudin-4 in ectopic endometrium suggests that claudin-3 and claudin-4 might play a pathogenic role in the formation of endometriosis.

[Expression of claudin-4 in eutopic and ectopic endometrium of women with endometriosis].

OBJECTIVE: To investigate the expression of claudin-4 in the eutopic and ectopic endometrium of women with endometriosis and evaluate the role of claudin-4 in the pathogenesis of endometriosis. METHODS: Thirty-five women with endometriosis and 35 controls were studied. Expression of claudin-4 was investigated using immunohistochemistry, western blot and RT-PCR, respectively. Morphologic change of tight junction was also observed in different kinds of endometria RESULTS: (1) Glandular epithelial cells of control endometrium and eutopic endometrium showed intact tight junctions in electron micrographs, whereas the morphology of tight junctions in ovarian endometriotic tissue was disrupted and collagen bundles could be easily detected. (2) The immunohistochemical staining of claudin-4 was localized to the glandular epithelial cell membrane. Deficient or weak staining was found in ovarian endometriotic tissues. In control endometrium, eutopic and ectopic endometrium of women with endometriosis, the expression of claudin-4 protein was 89 +/- 24, 84 +/- 22 and 27 +/- 14, respectively. Relative expression of claudin-4 mRNA was 14.5 +/- 6.8, 13.8 +/- 9.5 and 2.6 +/- 2.5, respectively. Expression of claudin-4 was significantly lower in the ectopic endometriotic tissue than in the eutopic endometrium and the control at both mRNA and protein levels (P<0.05). No significant difference was found between eutopic endometrium from women with endometriosis and control endometrium from women without endometriosis (P>0.05). CONCLUSION: Down-regulated expression of claudin-4 might play a pathogenic role in the formation of endometriosis.

[Influence of 4-aminopyridine on cell proliferation through inhibiting voltage-gated K+ channel in ovarian cancer].

OBJECTIVE: To study the inhibition of cell proliferation by 4-aminopyridine (4-AP) in the human ovarian cancer cell SKOV3. METHODS: The expression of voltage-gated K(+) channel on the SKOV3 cell line was detected by reverse transcription polymerase chain reaction. Inhibition of voltage-gated K(+) current by 4-AP through the whole-cell patch-clamp technique on SKOV3 cell line was recorded. The influence on the cell-cycle of the SKOV3 cell line by 4-AP was observed by flow cytometry and the inhibition of the cell proliferation was studied using methyl thiazolyl tetrazolium (MTT) method. RESULTS: Voltage-gated K(+) channel was expressed in SKOV3 cell. Exposure of the SKOV3 cell to 5 mmol/L 4-AP reduced K(+) current by 52.5%. The 4-AP at 5 mmol/L significantly effected the progression of cell cycle with a 72 h treatment of SKOV3 cell. Exponentially growing cells without inhibitors had a distribution of 39.7% in G(0)/G(1) phase, 57.3% in S phase, and 3.0% in G(2)/M phase. In 4-AP-treated cells, the proportion of G(0)/G(1) cells increased significantly to 62.3% (P < 0.05), while there was a significant decrease in S phase cells (36.2%, P < 0.05) and G(2)/M phase (1.4%, P < 0.05). Incubation of the SKOV3 cells with 0.1, 1, 5, 10, 15, 20 mmol/L 4-AP resulted in a concentration-dependent reduction in the number of viable cells as compared with the control, and the inhibition rate was 17.5%, 35.0%, 54.6%, 69.1%, 71.2%, 72.8% respectively (vs control, P < 0.01). CONCLUSION: The voltage-gated K(+) channels expressed by SKOV3 play an important role in SKOV3 cell proliferation.