Characterization of Metabolic Patterns in Mouse Oocytes during Meiotic Maturation.

Well-balanced and timed metabolism is essential for making a high-quality egg. However, the metabolic framework that supports oocyte development remains poorly understood. Here, we obtained the temporal metabolome profiles of mouse oocytes during in vivo maturation by isolating large number of cells at key stages. In parallel, quantitative proteomic analyses were conducted to bolster the metabolomic data, synergistically depicting the global metabolic patterns in oocytes. In particular, we discovered the metabolic features during meiotic maturation, such as the fall in polyunsaturated fatty acids (PUFAs) level and the active serine-glycine-one-carbon (SGOC) pathway. Using functional approaches, we further identified the key targets mediating the action of PUFA arachidonic acid (ARA) on meiotic maturation and demonstrated the control of epigenetic marks in maturing oocytes by SGOC network. Our data serve as a broad resource on the dynamics occurring in metabolome and proteome during oocyte maturation.

A metabolomic study on the effect of prenatal exposure to Benzophenone-3 on spontaneous fetal loss in mice.

Benzophenone-3 (BP-3) is widely used in a variety of cosmetics and is prevalent in drinking water or food, and women were under notable high exposure burden of BP-3. Reports show the associations between prenatal exposure to BP-3 and the risk of fetal loss, but its underlying mechanism remains largely unknown. Pregnant ICR mice were gavaged with BP-3 from gestational day (GD) 0 to GD 6 at doses of 0.1, 10 and 1000 mg/kg/day. The samples were collected on GD 12. Ultra-performance liquid chromatography coupled with mass spectrometry-based metabolomics was used to detect metabolome changes in fetal mice, the uterus and the placenta to identify the underlying mechanism. The results showed that the body weight and relative organ weights of the liver, brain and uterus of pregnant mice were not significantly changed between the control group and the treatment group. BP-3 increased fetal loss, and induced placental thrombosis and tissue necrosis with enhancement of platelet aggregation. Metabolomic analysis revealed that fructose and mannose metabolism, the TCA cycle, arginine and proline metabolism in the fetus, arginine and proline metabolism and biotin metabolism in the uterus, and arginine biosynthesis and pyrimidine metabolism in the placenta were the key changed pathways involved in the above changes. Our study indicates that exposure to BP-3 can induce placental thrombosis and fetal loss via the disruption of maternal and fetal metabolism in mice, providing novel insights into the influence of BP-3 toxicity on the female reproductive system.

Gestational diabetes mellitus is associated with the neonatal gut microbiota and metabolome.

BACKGROUND: Gestational diabetes mellitus (GDM) is a metabolic disease that occurs in pregnant women and increases the risk for the development of diabetes. The relationship between GDM and meconium microbiota and metabolome remains incompletely understood. METHODS: Four hundred eighteen mothers (147 women with GDM and 271 normal pregnant women) and their neonates from the GDM Mother and Child Study were included in this study. Meconium microbiota were profiled by 16S rRNA gene sequencing. Meconium and maternal serum metabolome were examined by UPLC-QE. RESULTS: Microbial communities in meconium were significantly altered in neonates from the GDM mothers. A reduction in alpha diversity was observed in neonates of GDM mothers. At the phylum level, the abundance of Firmicutes and Proteobacteria changed significantly in neonates of GDM mothers. Metabolomic analysis of meconium showed that metabolic pathways including taurine and hypotaurine metabolism, pyrimidine metabolism, beta-alanine metabolism, and bile acid biosynthesis were altered in GDM subjects. Several changed metabolites varying by the similar trend across the maternal serum and neonatal meconium were observed. CONCLUSION: Altogether, these findings suggest that GDM could alter the serum metabolome and is associated with the neonatal meconium microbiota and metabolome, highlighting the importance of maternal factors on early-life metabolism.

Mycobacterium tuberculosis evades macrophage defenses by inhibiting plasma membrane repair.

Induction of macrophage necrosis is a strategy used by virulent Mycobacterium tuberculosis (Mtb) to avoid innate host defense. In contrast, attenuated Mtb causes apoptosis, which limits bacterial replication and promotes T cell cross-priming by antigen-presenting cells. Here we show that Mtb infection causes plasma membrane microdisruptions. Resealing of these lesions, a process crucial for preventing necrosis and promoting apoptosis, required translocation of lysosomal and Golgi apparatus-derived vesicles to the plasma membrane. Plasma membrane repair depended on prostaglandin E(2) (PGE(2)), which regulates synaptotagmin 7 (Syt-7), the calcium sensor involved in the lysosome-mediated repair mechanism. By inducing production of lipoxin A(4) (LXA(4)), which blocks PGE(2) biosynthesis, virulent Mtb prevented membrane repair and induced necrosis. Thus, virulent Mtb impairs macrophage plasma membrane repair to evade host defenses.

Preliminary study on impacts of polystyrene microplastics on the hematological system and gene expression in bone marrow cells of mice.

Microplastics (MPs) are currently a global environmental pollutants and health hazards that caused by MPs cannot be ignored. However, studies on MP toxicity in mammals are scare. Here, we investigated the effects of two doses (0.1 mg and 0.5 mg) of 5 µm polystyrene microplastic (PS-MP) particles on the hematological system of mice through traditional toxicology experiments and assessed the related potential biological mechanisms using transcriptome sequencing analysis. The toxicological examinations showed that the 0.5 mg dose significantly decreased white blood cell count, increased Pit count, and inhibited the growth of colony-forming unit CFU-G, CFU-M and CFU-GM. Compared with the control group, there were 41 differentially expressed genes (DEGs) in the 0.1 mg-treated group and 32 significantly changed genes in 0.5 mg-treated group. Of note, eight genes were found to be significantly altered in both the PS-MP-treated groups. Gene ontology analysis showed that DEGs were mainly involved in T cell homeostasis, response to osmotic stress, extracellular matrix and structure organization, and metabolic process of NADP and nucleotides. In addition, pathway analysis revealed that the Jak/Stat pathway, pentose and glucuronate interconversions, nicotinate and nicotinamide metabolism, biosynthesis of unsaturated fatty acids, and the pentose phosphate pathway were involved in PS-MP-induced toxicity in mice. These results indicated that PS-MP exposure can cause hematotoxicity to some extent, impact gene expression, and disturb related molecular and biological pathways in mouse bone marrow cells. Our study provides fundamental data on the hematotoxicity of PS-MPs in terrestrial mammals that will help to further assess the corresponding health risks in these mammals.

Mycobacterium tuberculosis blocks crosslinking of annexin-1 and apoptotic envelope formation on infected macrophages to maintain virulence.

Macrophages infected with attenuated Mycobacterium tuberculosis strain H37Ra become apoptotic, which limits bacterial replication and facilitates antigen presentation. Here we demonstrate that cells infected with H37Ra became apoptotic after the formation of an apoptotic envelope on their surface was complete. This process required exposure of phosphatidylserine on the cell surface, followed by deposition of the phospholipid-binding protein annexin-1 and then transglutaminase-mediated crosslinking of annexin-1 through its amino-terminal domain. In macrophages infected with the virulent strain H37Rv, in contrast, the amino-terminal domain of annexin-1 was removed by proteolysis, thus preventing completion of the apoptotic envelope, which resulted in macrophage death by necrosis. Virulent M. tuberculosis therefore avoids the host defense system by blocking formation of the apoptotic envelope, which leads to macrophage necrosis and dissemination of infection in the lung.

ERp29 affects the migratory and invasive ability of human extravillous trophoblast HTR-8/SVneo cells via modulating the epithelial-mesenchymal transition.

Dysfunction of trophoblast metastasis into the endometrium is the main cause of pre-eclampsia (PE); however, the factors affecting this process are still unclear. In this study, we found that endoplasmic reticulum protein 29 (ERp29), one molecular chaperone of the endoplasmic reticulum, was aberrantly upregulated in the placenta of pre-eclamptic patients compared with healthy controls. Then, an in vitro study using human extravillous trophoblast HTR-8/SVneo cells showed that ERp29 upregulation could inhibit the migratory and invasive ability of HTR-8/SVneo cells, while ERp29 downregulation had the opposite effect. Mechanical experiments confirmed that ERp29 blocked trophoblast metastasis via inhibiting the process of epithelial-mesenchymal transition and affecting the Wnt/ß-catenin signaling pathway. In conclusion, this study revealed the important role of ERp29 in trophoblast metastasis and improved the mechanical understanding of PE occurrence.

Metabolomics study and meta-analysis on the association between maternal pesticide exposome and birth outcomes.

BACKGROUND: Pregnant women are exposed to a number of pesticides which are widely used in China. Their potential risks on reproduction and infants are still unknown. OBJECTIVE: We aimed to investigate whether infant's birth weight and length of gestation were associated with levels of various pesticides in maternal blood based on Nanjing Medical University (NMU) affiliated hospitals data and meta-analysis, and also to explore the possible intermediate metabolomics pathways. METHODS: Eligible subjects (n = 102) were included in this study from the affiliated hospitals of NMU. Gas chromatography tandem mass spectrometry (GC/MS) and Q-Exactive mass spectrometer (QE) were used to detect 37 pesticides (9 organophosphorus pesticides, 7 organochlorine pesticides, 5 carbamate pesticides, and 16 others) and 161 metabolites (53 in animo acid metabolism 47 in lipid metabolism, 18 in carbohydrate metabolism, 14 in nucleotide metabolism and 29 in other metabolisms) in maternal blood, respectively. Multi-linear regression and Bayesian kernel machine regression (BKMR) were performed to identify the association of single/mixed pesticide exposure in maternal blood with birth weight and length of gestation. Moreover, we conducted a meta-analysis including additional 2497 subjects to evaluate whether exposure to key pesticide, ß-hexachlorocyclohexane (ß-HCH) was associated with decreased birth weight globally. Mediation analysis was used to explore the metabolic alteration mediating the association between key pesticide exposure and birth outcomes. RESULTS: We found that decreased birth weight was significantly associated with increasing levels of mecarbam and ß-HCH. We did not find any association between length of gestation and these pesticides. Among pesticides with detection rate more than 50%, BKMR analysis found an overall negative association of mixed pesticides exposure with birth weight, and verified that ß-HCH was the key pesticide for such effect. Meta-analysis revealed a significantly negative association between exposure to ß-HCH and birth weight. Metabolomics identified three metabolites and five metabolites as significant mediators for the effect of mecarbam and ß-HCH, respectively, among which glyceraldehyde and its related glycerolipid metabolism and thyroxine and its related thyroid hormone metabolism were found to be the mostly enriched mediating metabolic pathway. CONCLUSIONS: Based on the comprehensive pesticide exposome and metabolome wide associational study combined with meta-analysis, we found that prenatal exposure to ß-HCH and mecarbam decreased birth weight via disrupting thyroid hormone metabolism and glyceraldehyde metabolism, providing new insights into the toxic effects of exposure to pesticides on birth outcomes.

ERp29 inhibition attenuates TCA toxicity via affecting p38/p53- dependent pathway in human trophoblast HTR-8/SVeno cells.

Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder occurred in pregnant women, and the mechanism for such disease is still unclear. The bioinformatics analysis of our previous study has revealed the abnormal expression of endoplasmic reticulum protein 29 (ERp29) in placental tissue of ICP patients. In this study, the function of ERp29 was further explored using in vitro model of ICP. The results showed that up-regulation of ERp29 occurred in TCA (taurocholic acid)-treated human trophoblast HTR-8/SVeno cells, and ERp29 inhibition reversed TCA toxicity via attenuating G2/M arrest and cell apoptosis. Mechanical study revealed ERp29 inhibition suppressed phosphorylation and kinase activity of p38, thus subsequently affecting expression and phosphorylation of p53 (ser18) as well as the transcriptional activity of p53. The conduction of this study might confirm the important role of ERp29 in ICP and which would be helpful for the development of target therapeutic method for ICP.

Prenatal exposure to the herbicide 2,4-D is associated with deficits in auditory processing during infancy.

INTRODUCTION: Despite widespread use, many herbicides and fungicides are not well studied for neurological effects. Fetal and infant brains are rapidly developing, yet the effects of early-life exposure to these classes of pesticides on visual and auditory function are unknown. Here we examined the effects of prenatal herbicide and fungicide exposure on infant grating visual acuity (VA) and auditory brainstem response (ABR). METHODS: 9 herbicides and 13 fungicides were measured in umbilical cord blood plasma from a cohort of infants in Fuyang County, China (n = 232). Grating VA and ABR latencies for waves I, III, V were measured at 3 time points: 6 weeks, 9 months, and 18 months. Outcomes included VA score, ABR wave V latency and ABR central conduction time (CCT [wave V- wave I]). Pesticides were analyzed as 3-level ordinal (non-detect [ND]/medium/high), or dichotomous (ND/detect), depending on detection rates. Linear mixed models were used to evaluate relations between pesticides and VA and ABR outcomes. RESULTS: 2,4-dichloroacetic acid (2,4-D), prometryn, simazine, and tetrahydrophthalamide (THPI, a metabolite of captan) were detected in 27%, 81%, 17%, and 16% of samples, respectively. Infants prenatally exposed to 2,4-D had slower auditory response times at 6 weeks. Infants with cord levels of 2,4-D > 1.17 ng/mL had wave V latencies that were 0.12 (95% CI: 0.03, 0.22) ms slower (p = 0.01) and overall CCTs that were 0.15 (95% CI:0.05, 0.25) ms slower (p = 0.003) than infants with non-detectable 2,4-D in their cord blood. No other statistically significant findings were observed for the other herbicides and fungicides or for the grating VA outcome. CONCLUSIONS: Prenatal exposure to the herbicide 2,4-D was associated with slower auditory signal transmission in early infancy. ABR latencies reflect auditory pathway maturation and longer latencies may indicate delayed auditory development.

A multi-method evaluation of the effects of Inflammatory cytokines (IL-1ß, IFN-γ, TNF-α) on pancreatic ß-cells.

We aimed to explore the effects of Inflammatory cytokines (IL-1ß, IFN-γ, TNF-α) on pancreatic ß-cells. CCK-8 assay showed that the cell viability decreased after 24 hr treatment of TNF-α, 48 hr of IFN-γ, and 84 hr of IL-1ß. EdU assay illustrated that after 24 hr treatment, there were significantly reduced EdU-labeled red fluorescence cells in TNF-α group while not in IFN-γ and IL-1ß groups. Flow Cytometry results displayed that TNF-α and IFN-γ groups increased apoptosis while IL-1ß group did not. Cell apoptosis results found that there was an increase in the S-phase population of IL-1ß and TNF-α groups, however, there was no significant difference in cell cycle between IFN-γ group and the control. TEM images showed that there were reduction in the number of granules and mitochondria in IL-1ß and IFN-γ groups, in particular paucity of insulin granules and mitochondria in TNF-α group. Radioimmunoassay results presented that TNF-α inhibited glucose-induced insulin secretion, while there were no significant changes in IL-1ß and IFN-γ groups when compared with the control. Metabolomic analysis found amino acid metabolism and Krebs cycle were the most robust altered metabolism pathways after inflammatory cytokines treatments. Overall, the altered amino acid metabolism and Krebs cycle metabolism might be important mechanisms of TNF-α induced mouse pancreatic ß-cells dysfuction.

The Serum microRNA Profile of Intrahepatic Cholestasis of Pregnancy: Identification of Novel Noninvasive Biomarkers.

BACKGROUND/AIMS: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disease that significantly increases the risk of fetal complications. Here, we measured serum miRNA levels in ICP patients to identify candidate biomarkers for ICP. METHODS: We used the Agilent miRNA array followed by reverse transcription-polymerase chain reaction assays to identify and validate the serum miRNA profiles of 40 pregnant women with ICP and 40 healthy pregnant controls. We used bioinformatics to identify metabolic processes related to differentially expressed miRNAs. RESULTS: The expression levels of three miRNAs (miR-371a- 5p, miR-6865-5p, and miR-1182) were significantly increased in ICP patients compared to controls; the areas under the receiver operating characteristic (ROC) curves (AUCs) were 0.771, 0.811, and 0.798, respectively. Multiple logistic regression analysis showed that a combination of the levels of the three miRNAs afforded a greater AUC (0.845), thus more reliably diagnosing ICP. The levels of all three miRNAs were positively associated with that of total bile acids. Furthermore, bioinformatics analysis indicated that the three miRNAs principally affected lipid phosphorylation, apoptosis, and the MAPK signaling pathway. CONCLUSION: This preliminary work improves our understanding of serum miRNA changes in pregnant women with ICP. The three miRNAs may serve as novel noninvasive biomarkers of ICP.

Meta-analysis on the effectiveness of team-based learning on medical education in China.

BACKGROUND: Team-based learning (TBL) has been adopted as a new medical pedagogical approach in China. However, there are no studies or reviews summarizing the effectiveness of TBL on medical education. This study aims to obtain an overall estimation of the effectiveness of TBL on outcomes of theoretical teaching of medical education in China. METHODS: We retrieved the studies from inception through December, 2015. Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Wanfang Database, Chinese Scientific Journal Database, PubMed, EMBASE and Cochrane Database were searched. The quality of included studies was assessed by the Newcastle-Ottawa scale. Standardized mean difference (SMD) was applied for the estimation of the pooled effects. Heterogeneity assumption was detected by I2 statistics, and was further explored by meta-regression analysis. RESULTS: A total of 13 articles including 1545 participants eventually entered into the meta-analysis. The quality scores of these studies ranged from 6 to 10. Altogether, TBL significantly increased students' theoretical examination scores when compared with lecture-based learning (LBL) (SMD = 2.46, 95% CI: 1.53-3.40). Additionally, TBL significantly increased students' learning attitude (SMD = 3.23, 95% CI: 2.27-4.20), and learning skill (SMD = 2.70, 95% CI: 1.33-4.07). The meta-regression results showed that randomization, education classification and gender diversity were the factors that caused heterogeneity. CONCLUSIONS: TBL in theoretical teaching of medical education seems to be more effective than LBL in improving the knowledge, attitude and skill of students in China, providing evidence for the implement of TBL in medical education in China. The medical schools should implement TBL with the consideration on the practical teaching situations such as students' education level.

Metabolome-wide association study identified the association between a circulating polyunsaturated fatty acids variant rs174548 and lung cancer.

Quantitative trait loci (QTLs) are widely used as instruments to infer causal risk factors of diseases based on the idea of mendelian randomization. Plasma metabolites can serve as risk factors of cancer, and the heritability of many circulating metabolites was high. We conducted a metabolome-wide association study (MWAS) to systematically investigate the effects of genetic variants on metabolites and lung cancer based on published genome-wide association study (GWASs) and metabolic-QTL (mQTL) study. Then we confirmed the results by subsequent genetic and metabolic validations and inferred the causal relationship between identified metabolites and lung cancer through genetic variant(s). We firstly identified six polyunsaturated fatty acids (PUFAs) represented by rs174548-linked haplotype were significantly associated with lung cancer risk in a Chinese GWAS (2311 cases and 3077 controls). Rs174548 was further confirmed to be associated with lung cancer in 13 821 Europeans and 18 471 Asians (ORmeta = 0.87, Pmeta = 1.76 × 10-15) and the effect was much stronger in females (Pinteraction = 6.00 × 10-4). We next validated rs174548-plasma PUFA association in 253 Chinese subjects (ß = -0.57, P = 1.68 × 10-3). Rs174548 was also found associated with FADS1 (the major fatty acid desaturase of identified PUFAs) expression in liver tissues. Taken together, we found that rs174548 was associated with both PUFAs and lung cancer. Because rs174548 was the only mQTL variant of PUFAs reported by previous GWASs and explained a large proportion of heritability, we proposed that plasma PUFAs could be causally associated with lung cancer based on the idea of mendelian randomization. These findings provide a diet-related risk factor and may have important implications for prevention on lung cancer.

Interaction between Y chromosome haplogroup O3* and 4-n-octylphenol exposure reduces the susceptibility to spermatogenic impairment in Han Chinese.

Certain genetic background (mainly Y chromosome haplogroups, Y-hg) may modify the susceptibility of certain environmental exposure to some diseases. Compared with respective main effects of genetic background or environmental exposure, interactions between them reflect more realistic combined effects on the susceptibility to a disease. To identify the interactions on spermatogenic impairment, we performed Y chromosome haplotyping and measurement of 9 urinary phenols concentrations in 774 infertile males and 520 healthy controls in a Han Chinese population, and likelihood ratio tests were used to examine the interactions between Y-hgs and phenols. Originally, we observed that Y-hg C and Y-hg F* might modify the susceptibility to male infertility with urinary 4-n-octylphenol (4-n-OP) level (Pinter = 0.005 and 0.019, respectively). Subsequently, based on our results, two panels were tested to identify the possible protective sub-branches of Y-hg F* to 4-n-OP exposure, and Y-hg O3* was uncovered to interact with 4-n-OP (Pinter = 0.019). In conclusion, while 4-n-OP shows an adverse effect on spermatogenesis, Y-hg O3* makes individuals more adaptive to such an effect for maintaining basic reproductive capacity.

Comparative analysis of macaque and human sperm proteomes: Insights into sperm competition.

Male macaques produce faster sperm than male humans due to a higher pressure of sperm competition in macaques. To explore the molecular basis of this biological difference, we firstly constructed macaque and human sperm proteomes using LC-MS/MS. We then detected the positively selected genes specifically on the branch of macaque based on branch-site likelihood method. We identified 197 positively selected genes specifically on the branch of macaque that are unselected in corresponding human orthologs. These genes are highly associated with mitochondria and axoneme that directly drive sperm motility. We further compared the ultrastructural differences of the midpiece between macaque and human sperms to provide evidence for our findings using transmission electron microscopy. In conclusion, our results provide potential molecular targets for explaining the different phenotypes under sperm competition between macaques and humans, and also provide resources for the analysis of male fertility.

The effects of triclosan on pluripotency factors and development of mouse embryonic stem cells and zebrafish.

Triclosan (TCS) poses potential risks to reproduction and development due to its endocrine-disrupting properties. However, the mechanism of TCS's effects on early embryonic development is little known. Embryonic stem cells (ESC) and zebrafish embryos provide valuable models for testing the toxic effects of environmental chemicals on early embryogenesis. In this study, mouse embryonic stem cells (mESC) were acutely exposed to TCS for 24 h, and general cytotoxicity and the effect of TCS on pluripotency were then evaluated. In addition, zebrafish embryos were exposed to TCS from 2- to 24-h post-fertilization (hpf), and their morphology was evaluated. In mESC, alkaline phosphatase staining was significantly decreased after treatment with the highest concentration of TCS (50 µM). Although the expression levels of Sox2 mRNA were not changed, the mRNA levels of Oct4 and Nanog in TCS-treated groups were significantly decreased compared to controls. In addition, the protein levels of Oct4, Sox2 and Nanog were significantly reduced in response to TCS treatment. MicroRNA (miR)-134, an expression inhibitor of pluripotency markers, was significantly increased in TCS-treated mESC. In zebrafish experiments, after 24 hpf of treatment, the controls had developed to the late stage of somitogenesis, while embryos exposed to 300 µg/L of TCS were still at the early stage of somitogenesis, and three genes (Oct4, Sox2 and Nanog) were upregulated in treated groups when compared with the controls. The two models demonstrated that TCS may affect early embryonic development by disturbing the expression of the pluripotency markers (Oct4, Sox2 and Nanog).

[A investigation of thirdhand smoke pollution in 3 types of places of Nanjing, 2014].

OBJECTIVE: To investigate thirdhand smoke (THS) pollution in certain places of Nanjing, as well as to analyze its distribution characteristics. METHODS: From March to May, 2014, we selected 3 types of places (residencies, public places and transportation vehicles) that were close to people's living in Jianye,Yuhua,Jiangning,Xuanwu,Gulou and Pukou districts of Nanjing city.For each of the above 3 types of places, 2-3 smoking and non-smoking (smoking ban) locations were investigated, totally 51 locations, 9-10 samples were collected each location, totally 477 samples. The surface wipe sampling method in conjunction with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was utilized to quantify the levels of nicotine that served as the tracer of THS pollution.One-way ANOVA and t-tests were employed to compare the levels of nicotine collected at different places and locations. RESULTS: Totally 477 samples were collected in this study, of which 27.0% was from residencies (129/477), 61.0% (291/477) from public places and 11.9% (57/477) from transportations. The levels of indoor surface nicotine in smoking residences, public places and transportations were (214 ± 55),(1 408 ± 177) and (1 511 ± 785) µg/m(2), respectively, which were all higher than those in the corresponding non-smoking places ((23 ± 9),(62 ± 11), and (46 ± 15) µg/m(2); t values were 13.79, 13.15, 3.45, respectively. P values were <0.001, <0.001 and 0.006, respectively).In the smoking places, the levels of surface nicotine on walls, desks, sofas, cabinets, door backsides and air conditioning openings were (171 ± 62),(232 ± 38),(373 ± 151),(903 ± 239), (978 ± 212), (1 721 ± 517) µg/m(2) (F = 7.06, P = 0.009).In the smoking condition, the levels of surface nicotine collected from public places were higher (F = 9.25, P = 0.024), while under non-smoking (smoking ban) conditions, the levels of surface nicotine collected from residences were lower (F = 7.88, P < 0.001). CONCLUSION: THS pollution was widespread in public places, residences and transportations in Nanjing city, which was more serious in the smoking environments than non-smoking (smoking ban) environments; the contamination was less serious in non-smoking (smoking ban) private residences; in the smoking condition, the levels of surface nicotine were relatively high at locations close to air conditioning openings, door backsides and cabinets.

Combined effects of urinary phytoestrogens metabolites and polymorphisms in metabolic enzyme gene on idiopathic male infertility.

Phytoestrogens are plant-derived compounds that may interact with estrogen receptors and mimic estrogenic effects. It remains unclear whether the individual variability in metabolizing phytoestrogens contributes to phytoestrogens-induced beneficial or detrimental effects. Our aim was to determine whether there is any interaction between metabolic rates (MR) of phytoestrogens and genetic polymorphisms in related xenobiotic metabolizing enzyme genes. MR was used to assess phytoestrogen exposure and individual metabolic ability. The amount of phytoestrogens in urine was measured by ultra-high performance liquid chromatography-tandem mass spectrometry in 600 idiopathic infertile male patients and 401 controls. Polymorphisms were genotyped using the SNPstream platform combined with the Taqman method. Prototypes and metabolites of secoisolariciresinol (SEC) have inverse effects on male reproduction. It was found that low MR of SEC increased the risk of male infertility (OR 2.49, 95 % CI 1.78, 3.48, P trend = 8.00 × 10(-8)). Novel interactions were also observed between the MR of SEC and rs1042389 in CYP2B6, rs1048943 in CYP1A1, and rs1799931 in NAT2 on male infertility (P inter = 1.06 × 10(-4), 1.14 × 10(-3), 3.55 × 10(-3), respectively). By analyzing the relationships between urinary phytoestrogen concentrations, their metabolites and male infertility, we found that individual variability in metabolizing SEC contributed to the interpersonal differences in SEC's effects on male reproduction.

Trophectoderm morphology predicts outcomes of pregnancy in vitrified-warmed single-blastocyst transfer cycle in a Chinese population.

PURPOSE: In this study, we estimated the effect of blastocoele expansion, ICM and TE quality after warming and culture on the rates of clinical pregnancy, live birth and miscarriage in vitrified-warmed single-blastocyst transfer cycle in a Chinese population. METHODS: A retrospective analysis of 263 cycles of vitrified-warmed single-blastocyst transfers was performed. RESULTS: The blastocysts with higher TE grade significantly increased the rates of clinical pregnancy (OR = 0.59, 95 % CI, 0.35-0.99, P = 0.045, grade (A + B) vs grade C) and live birth (OR = 0.55, 95 % CI, 0.32-0.94, P = 0.029, grade (A + B) vs grade C). And the association between TE grade and the rate of live birth didn't change after the number of repeated cycles was adjusted (OR = 0.55, 95 % CI, 0.32-0.95, P = 0.033, grade (A + B) vs grade C). The number of repeated cycles was a confounding factor significantly different between the live birth and no live birth groups. By contrast, neither blastocoele expansion nor inner cell mass was statistically related to the rates of clinical pregnancy, live birth and miscarriage. CONCLUSIONS: Our data firstly provided the evidence that TE grading, but not ICM grading, was significantly associated with the clinical pregnancy rate and live birth rate in vitrified-warmed blastocyst transfer cycles in a Chinese population. TE morphology may help predict outcomes of pregnancy in single-blastocyst transfer.