Effect of prenatal exposure to phthalates on birth weight of offspring: A meta-analysis.

Prenatal exposure to phthalates is common. However, its effect on birth weight has always been met with conflicting conclusions. To explore the effects of prenatal phthalate exposure on neonatal weight, we searched PubMed, Web of Science (WOS), Cochrane Library, and Embase databases for articles published up to October 24, 2023. Observational studies with 95% confidence intervals (CI) were included. Our findings indicate no significant association between either mixed exposure effects or single phthalate metabolites and offspring birth weight when monitoring maternal urine phthalate metabolites. When stratified by sex, ΣHMWPs and MMP significantly reduced the birth weight of female offspring (ΣHMWPs: Pooled ß = -62.08, 95%CI: -123.11 to -1.05, P = 0.046; MMP: Pooled ß = -10.77, 95%CI: -18.74 to -2.80, P = 0.008). The results of subgroup analysis showed that ΣPAEs and ΣDEHP significantly decreased birth weight in the specific gravity correction group (ΣPAEs: Pooled estimates = -29.31, 95%CI: -58.52 to -0.10, P = 0.049; ΣDEHP: Pooled estimates = -18.25, 95%CI: -33.03 to -3.47, P = 0.016), and MECPP showed a positive correlation in the creatinine correction group (MECPP: Pooled estimates = 18.45, 95%CI: 0.13 to 36.77, P = 0.048). MEP and MBzP were negatively associated with birth weight in the no adjustment for gestational age group (MEP: Pooled estimates = -7.70, 95%CI: -14.19 to -1.21, P = 0.020; MBzP: Pooled estimates = -9.55, 95%CI: -16.08 to -3.03, P = 0.004). To make the results more convincing, more high-quality studies with large samples are urgently required.

Differential expression and significance of 5-hydroxymethylcytosine modification in hepatitis B virus carriers and patients with liver cirrhosis and liver cancer.

BACKGROUND: The relationship between hepatitis B surface antigen (HBsAg)-positive carrier status and liver cancer has been extensively studied. However, the epigenetic changes that occur during progression from HBsAg-positive carrier status or cirrhosis to liver cancer are unknown. The epigenetic modification of DNA hydroxymethylation is critical in tumor development. Further, 5-hydroxymethylcytosine (5hmC) is an important base for DNA demethylation and epigenetic regulation. It is also involved in the assembly of chromosomes and the regulation of gene expression. However, the mechanism of action of 5hmC in HBsAg-positive carriers or patients with cirrhosis who develop liver cancer has not been fully elucidated. AIM: To investigate the possible epigenetic mechanism of HBsAg-positive carriers and hepatocellular carcinoma (HCC) progression from cirrhosis. METHODS: Forty HBsAg-positive carriers, forty patients with liver cirrhosis, and forty patients with liver cancer admitted to the First People's Hospital of Yongkang between March 2020 and November 2021 were selected as participants. Free DNA was extracted using a cf-DNA kit. cfDNA was extracted by 5hmC DNA sequencing for principal component analysis, the expression profiles of the three groups of samples were detected, and the differentially expressed genes (DEGs) modified by hydroxymethylation were screened. Bioinformatic analysis was used to enrich DEGs, such as in biological pathways. RESULTS: A total of 16455 hydroxymethylated genes were identified. Sequencing results showed that 32 genes had significant 5hmC modification differences between HBsAg carriers and liver cancer patients, of which 30 were upregulated and 2 downregulated in patients with HCC compared with HBsAg-positive carriers. Significant 5hmC modification differences between liver cirrhosis and liver cancer patients were identified in 20 genes, of which 17 were upregulated and 3 were downregulated in patients with HCC compared with those with cirrhosis. These genes may have potential loci that are undiscovered or unelucidated, which contribute to the development and progression of liver cancer. Analysis of gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes showed that the major signaling pathways involved in the differential genes were biliary secretion and insulin secretion. The analysis of protein interactions showed that the important genes in the protein-protein interaction network were phosphoenolpyruvate carboxykinase and solute carrier family 2. CONCLUSION: The occurrence and development of liver cancer involves multiple genes and pathways, which may be potential targets for preventing hepatitis B carriers from developing liver cancer.

The effect of ambient ozone exposure on three types of diabetes: a meta-analysis.

BACKGROUND: Ozone as an air pollutant is gradually becoming a threat to people's health. However, the effect of ozone exposure on risk of developing diabetes, a fast-growing global metabolic disease, remains controversial. OBJECTIVE: To evaluate the impact of ambient ozone exposure on the incidence rate of type 1, type 2 and gestational diabetes mellitus. METHOD: We systematically searched PubMed, Web of Science, and Cochrane Library databases before July 9, 2022, to determine relevant literature. Data were extracted after quality evaluation according to the Newcastle Ottawa Scale (NOS) and the agency for healthcare research and quality (AHRQ) standards, and a meta-analysis was used to evaluate the correlation between ozone exposure and type 1 diabetes mellitus (T1D), type 2 diabetes mellitus (T2D), and gestational diabetes mellitus (GDM). The heterogeneity test, sensitivity analysis, and publication bias were performed using Stata 16.0. RESULTS: Our search identified 667 studies from three databases, 19 of which were included in our analysis after removing duplicate and ineligible studies. Among the remaining studies, three were on T1D, five were on T2D, and eleven were on GDM. The result showed that ozone exposure was positively correlated with T2D [effect size (ES) = 1.06, 95% CI: 1.02, 1.11] and GDM [pooled odds ratio (OR) = 1.01, 95% CI: 1.00, 1.03]. Subgroup analysis demonstrated that ozone exposure in the first trimester of pregnancy might raise the risk of GDM. However, no significant association was observed between ozone exposure and T1D. CONCLUSION: Long-term exposure to ozone may increase the risk of T2D, and daily ozone exposure during pregnancy was a hazard factor for developing GDM. Decreasing ambient ozone pollution may reduce the burden of both diseases.

Pyridoxal 5'-phosphate alleviates prenatal pyridaben exposure-induced anxiety-like behaviors in offspring.

Pyridaben (PY) is a widely used organochlorine acaricide, which can be detected in the peripheral blood of pregnant women. Available evidence suggests that PY has reproductive toxicity. However, it remains uncertain whether prenatal PY exposure impacts neurobehavioral development in offspring. Here, we administered PY to pregnant mice at a dose of 0.5 and 5 mg kg-1 day-1 via gavage and observed anxiety-like behaviors in PY offspring aged five weeks. We then integrated the metabolome and transcriptome of the offspring's brain to explore the underlying mechanism. Metabolome data indicated that the vitamin B6 metabolism pathway was significantly affected, and the pyridoxal 5'-phosphate (PLP) concentration and the active form of vitamin B6 was significantly reduced. Moreover, the transcriptome data showed that both PLP generation-related Pdxk and anxiety-related Gad1 were significantly down-regulated. Meanwhile, there was a decreasing trend in the concentration of GABA in the hippocampal DG region. Next, we supplemented PLP at a dose of 20 mg kg-1 day-1 to the PY offspring via intraperitoneal injection at three weeks. We found up-regulated expression of Pdxk and Gad1 and restored anxiety-like behaviors. This study suggests that prenatal exposure to PY can disrupt vitamin B6 metabolism, reduce the concentration of PLP, down-regulate the expression levels of Pdxk and Gad1, inhibit the production of GABA, and ultimately lead to anxiety-like behaviors in offspring.

Feasibility analysis of incorporating infertility into medical insurance in China.

In recent years, the incidence of infertility has been increasing gradually, while the natural rate of population growth is declining or even at zero growth. China is observed to enter a depth of aging society, leading to more severe infertility. Infertility patients face many predicaments, and many unreasonable behaviors existed in seeking medical diagnosis and treatment, of which the main influencing factor is economic condition. In China, Beijing has taken the lead in providing medical insurance for 16 assisted reproductive technology items. Assuming that all infertile couples with the option of assisted reproduction are treated, there would be a huge market gap. The reimbursement rate can be adjusted based on some factors within the affordable range of the medical insurance fund. Progress on infertility coverage in other countries was also reviewed. This paper cited the data of medical insurance funds in China in the recent 4 years as a reference. Based on the data, it is not currently able to cover all the costs of infertility diagnosis and treatment during the research period, but it is feasible to access selective reimbursement and subsidies for those in particular need as well as to develop some commercial insurances. There is a big gap in the application of assisted reproductive technology between China and developed countries. More comprehensive and constructive policies should be formulated countrywide to standardize the market. Assisted reproduction-related technologies and acceleration of the domestic medical apparatus and instrument replacement should be improved to reduce the cost.

Serum CHI3L1 as a diagnostic marker and risk factor for liver fibrosis in HBeAg-negative chronic hepatitis B.

Chronic hepatitis B (CHB) as the major inducement of hepatocellular carcinoma and cirrhosis, imposes a heavy health burden upon patients. This research aims to investigate the diagnostic value of serum chitinase 3-like 1 (CHI3L1) in hepatitis B e antigen (HBeAg)-negative CHB liver fibrosis (LF) and to analyze the risk factors. We selected 78 patients with HBeAg-negative CHB admitted to our hospital between October 2018 and October 2019, and grouped them (F0,1 group, n=38; F2-4 group, n=40) based on their stages evaluated by the METAVIR scoring system. Cubital venous blood was collected from patients in both groups to quantify the content of CHI3L1 after serum extraction. The correlation of CHI3L1 in CHB with LF diagnostic markers fibrosis 4 (FIB-4) and γ-glutamyltranspeptidase (GGT) to platelet (PLT) ratio (GPR) as well as LF staging was analyzed. The diagnostic value of serum CHI3L1 in HBeAg-negative CHB fibrosis staging was analyzed by receiver operating characteristic (ROC) curve, and the multivariate analysis of the risk factors for FB in HBeAg-negative CHB patients was performed using the Logistic regression model. This study found that serum CHI3L1 was positively correlated not only with LF markers (FIB-4, GPR), but also with LF staging. Serum CHI3L1 had high diagnostic efficiency for LF staging, with the sensitivity and specificity of 80.00% and 71.05%, respectively. In addition, CHI3L1, FIB-4, and GPR were identified to be the risk factors for LF in HBeAg-negative CHB. In conclusion, serum CHI3L1 can be used as a diagnostic marker and risk factor for LF in patients with HBeAg-negative CHB.

Environmental chemical exposure dynamics and machine learning-based prediction of diabetes mellitus.

BACKGROUND: With dramatically increasing prevalence, diabetes mellitus has imposed a tremendous toll on individual well-being. Humans are exposed to various environmental chemicals, which have been postulated as underappreciated but potentially modifiable diabetes risk factors. OBJECTIVES: To determine the utility of environmental chemical exposure in predicting diabetes mellitus. METHODS: A total of 8501 eligible participants from NHANES 2005-2016 were randomly assigned to a discovery (N = 5953) set and a validation (N = 2548) set. We applied random forest (RF) and least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation in the discovery set to select features, and built an optimal model to predict diabetes mellitus, blood insulin, fasting plasma glucose (FPG) and 2-h plasma glucose after oral glucose tolerance test (2-h PG after OGTT). RESULTS: The machine learning model using LASSO regression predicted diabetes with an area under the receiver operating characteristics (AUROC) of 0.80 and 0.78 in the discovery set and validation set, respectively. The linear model predicted blood insulin level with an R2 of 0.42 and 0.40 in the discovery set and validation set, respectively. For FPG, the discovery set and validation set yielded an R2 of 0.16 and 0.15, respectively. For 2-h PG after OGTT, the discovery set and validation set yielded an R2 of 0.18 and 0.17, respectively. CONCLUSION: We used environmental chemical exposure, constructed machine learning models and achieved relatively accurate prediction for diabetes, emphasizing the predictive value of widespread environmental chemicals for complicated diseases.

Effects of glufosinate-ammonium on male reproductive health: Focus on epigenome and transcriptome in mouse sperm.

Glufosinate-ammonium (GLA) is a widely used herbicide with emerging concern over its neural and reproductive toxicity. To uncover potential effects of GLA on male reproductive health in mammals, adult male C57BL/6J mice were administered 0.2 mg/kg·d GLA for 5 weeks. After examination on fertility, testis histology and semen quality in the GLA group, we performed deep sequencing to identify repressive epigenetic marks including DNA methylation and histone modifications (H3K27me3 and H3K9me3), together with mRNA transcript levels in sperm. Then, we integrated multi-omics sequencing data to comprehensively explore GLA-induced epigenetic and transcriptomic alterations. We found no significant difference either on fertility, testis histology or semen quality-related indicators. As for epigenome, the protein level of H3K27me3 was significantly increased in GLA sperm. Next generation sequencing showed alterations of these epigenetic marks and extensive transcription inhibition in sperm. These differential repressive marks were mainly distributed at intergenic regions and introns. According to results by Gene Ontology enrichment analysis, both differentially methylated and expressed genes were mainly enriched in pathways related to synapse organization. Subtle differences in genomic imprinting were also observed between the two groups. These results suggested that GLA predominantly impaired sperm epigenome and transcriptome in mice, with little effect on fertility, testis histology or semen quality. Further studies on human sperm using similar strategies need to be conducted for a better understanding of the male reproductive toxicity of GLA.

Evaluation of atrazine neurodevelopment toxicity in vitro-application of hESC-based neural differentiation model.

Atrazine is one of the widely used herbicides in the world and most of the current researches on atrazine neurodevelopment toxicity have focused on rodents or zebrafish models in vivo, resulting in relatively high cost, time consumption, and lower translational value to identify its hazard for the developing brain. Major international initiatives have pushed forward to convert the traditional animal-based developmental toxicity tests to in vitro assays using human cells to detect and predict chemical health hazards. In this study, we presented a human neural differentiation model based on human embryonic stem cells (hESC) that can be used to test toxicity at different stages of neural differentiation in vitro. hESC were differentiated into neural stem cells (NSC) and then terminally differentiated towards mixed neurons and glial cells for 21 days. Cell survival, proliferation, cell cycle, apoptosis, and gene expression levels were examined. Our results demonstrated that atrazine inhibited the proliferation of hESC and NSC, and showed different toxic sensitivity on these two kinds of cells. Also, atrazine blocked the NSC cell cycle G1 phase via down-regulating CCND1, CDK2, and CDK4, with no obvious effect on apoptosis. In addition, atrazine curbed EB spontaneous differentiation and NSC-induced neurons and glia cells differentiation. Atrazine altered genes expression levels of PAX6, TUBB3, NCAM1, GFAP, TH, NR4A1, and GRIA1. From the data we obtained, we recognized that the dopaminergic system was not the only target of atrazine neurotoxicity, glutamatergic neurons and astrocytes were also adversely affected.

Effects of exposure to urban particulate matter SRM 1648a during pregnancy on the neurobehavioral development of offspring mice.

The development of the nervous system is crucial to a child's health. However, the nervous system is also susceptible to a variety of factors during development. To date, epidemiological studies have reported controversial results on the relationship between prenatal exposure to particulate matter (PM) and neurobehavioral development. Thus, we investigated the effect of PM exposure during pregnancy on the neurobehavioral development of offsprings. Adult C57BL/6 mice were exposed to PM from gestation day (GD) 0.5-21 by the intratracheal instillation. The daily exposure doses were 250 µg/kg.b.w and 2500 µg/kg.b.w respectively. The offspring mice began behavioral tests at the 5th week. We assessed neurobehavioral development, and the gene expression level changes in the mouse hippocampus using RNA-seq. In the open field test, the movement distance in the central area was significantly decreased in the high-dose group. Serum free triiodothyronine (FT3) levels were significantly increased in male offspring mice with prenatal high-dose PM exposure. The RNA-seq results suggested that the Prkca, Med12l, Ep300, and Slc16a10 in the thyroid hormone signaling pathway were significantly decreased in offspring mice in the high-dose group. Our data showed that prenatal PM exposure caused the offspring mice's anxiety-like behaviors and increased serum FT3 levels. The changes in thyroid hormone pathway-related genes might be the causes of the above series of changes.

Multiple 'omics'-analysis reveals the role of prostaglandin E2 in Hirschsprung's disease.

The etiology and pathogenesis of Hirschsprung's disease (HSCR) remain largely unknown. We examined colon tissues from three independent populations with a combined analysis of metabolomics, transcriptomics and proteomics to understand HSCR pathogenesis, according to which mouse model was used to examine prostaglandin E2 (PGE2) induced clinical presentation of HSCR. SH-SY5Y and SK-N-BE(2) cell lines were studied for PGE2 inhibited cell migration through EP2. Our integrated multiple 'omics'-analysis suggests that the levels of PGE2, the expression of the gene encoding PGE2 receptor (EP2), and PGE2 synthesis enzyme genes (PTGS1 and PTGES) increased in HSCR colon tissues, together with a decreased synthesis of PGE2-related byproducts. In vivo, the pregnant mice treated with PGE2 gave birth to offspring with the decrease of ganglion cells in their colon and gut function. In in vitro study, when EP2 was blocked, the PGE2-inhibited cell migration was recovered. Our study identified a novel pathway highlighting the link between expression of PTGS1 and PTGES, levels of PGE2, expression of PTGER2, and neural crest cell migration in HSCR, providing a novel strategy for future diagnosis and prevention of HSCR.

Associations of maternal exposure to fine particulate matter constituents during pregnancy with Apgar score and duration of labor: A retrospective study in Guangzhou, China, 2012-2017.

BACKGROUND: Limited evidence is available for demonstrating effects of prenatal PM2.5 and its components exposure on Apgar score and duration of labor. OBJECTIVE: We sought to investigate the associations between PM2.5 constituents, Apgar score and duration of labor, and evaluated the potential mediating role of duration of labor. METHODS: This study included 5396 participants. The V4·CH.02 was applied to assessing exposure to PM2.5 constituents. The associations between PM2.5 constituents Apgar score and duration of labor were examined by multivariate linear regression. Mediation analysis was conducted to estimate the potential mediation effect of duration of labor. RESULTS: Trimester-specific exposure to soil dust was significantly associated with 1-min Apgar score (1st trimester: OR: 1.03, 95% CI:0.97, 1.10; 2nd trimester: OR: 1.07, 95% CI: 1.01, 1.14; 3rd trimester: OR: 1.07, 95% CI: 1.01, 1.13), duration of first stage of labor (1st trimester: ß: 0.32, 95% CI: 0.07, 0.58; 2nd trimester: ß: 0.27, 95% CI: 0.04, 0.51; 3rd trimester: ß: 0.37, 95% CI: 0.13, 0.61) and duration of second stage of labor (1st trimester: ß: 0.04, 95% CI: -0.00, 0.09; 2nd trimester: ß: 0.05, 95% CI: 0.01, 0.10; 3rd trimester: ß: 0.05, 95% CI: 0.00, 0.09). The duration of labor mediated the relationship between soil dust and 1-min Apgar score. CONCLUSION: This study demonstrated that prenatal exposure to soil dust was significantly associated with the risk of abnormal 1-min Apgar score and extended stage of labor.

Glufosinate-Ammonium Induced Aberrant Histone Modifications in Mouse Sperm Are Concordant With Transcriptome in Preimplantation Embryos.

Glufosinate-ammonium (GLA) is a widely used herbicide with emerging concern over its male reproductive toxicity. Abnormalities in sperm histone modification induced by GLA exposure observed in our previous study aroused our interest in whether such alterations could further affect embryonic gene expression. Here we administered adult male mice with 0.2 mg/kg⋅day of GLA for 5 weeks to collect their sperm or 4-cell embryos after copulation. Cleavage Under Targets and Tagmentation (CUT&Tag) sequencing showed alterations of sperm H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 acetylation (H3K27ac), which are active histone modification marks involved in embryo development, while RNA sequencing identified differentially expressed genes in 4-cell embryos. Differentially H3K4me3 and H3K27ac occupied regions were mainly distributed at the gene promoters and putative enhancers, and were enriched in pathways related to the immune system and nervous system. Integrative analysis of these sequencing data showed that genes such as Mgl2 with increased H3K4me3 and H3K27ac in sperm were up-regulated in embryos, and vice versa for genes such as Dcn. Additionally, differentially occupied H3K4me3 and H3K27ac in sperm were linked to gene expression changes in both paternal and maternal alleles of 4-cell embryos. In conclusion, GLA-induced changes in sperm H3K4me3 and H3K27ac are concordant with gene expression in preimplantation embryos, which might further affect embryo development and offspring health.

Degradation of polycarbonate to produce bisphenol A catalyzed by imidazolium-based DESs under metal-and solvent-free conditions.

Bisphenol A (BPA) is an important chemical raw material, but the traditional preparation process of BPA is costly and complicated, so it is necessary to find an efficient and environmentally friendly method for the production of BPA. Deep eutectic solvents (DESs) have attracted widespread attention due to their low cost, low toxicity, low melting point, non-volatilization, easy preparation, recyclablility and biodegradability. In this work, a series of imidazolium-based DESs were synthesized and used for the degradation of polycarbonate (PC), and BPA was obtained from the methanolysis of PC catalyzed by DESs under metal- and solvent-free conditions. It was found that imidazolium-based DES [EmimOH]Cl-2Urea showed excellent catalytic activity and reusability. Under the optimized reaction conditions (the mass ratio of DES to PC is 0.1 : 1, the molar ratio of CH3OH to PC is 5 : 1, 120 °C, reaction time 2 h), the PC conversion and BPA yield were almost 100% and 98%, respectively. Moreover, the kinetics of methanolysis catalyzed by [EmimOH]Cl-2Urea was investigated in the temperature range 100-120 °C, and the results indicated that it is a pseudo-first order reaction with an activation energy of 133.59 kJ mol-1. In addition, a possible catalytic mechanism of PC methanolysis is proposed.

Effects of Microbiota on the Treatment of Obesity with the Natural Product Celastrol in Rats.

Background: Obesity has become one of the most serious issues threatening the health of humankind, and we conducted this study to examine whether and how celastrol protects against obesity. Methods: We fed male Sprague-Dawley rats a high-fat diet and administered celastrol to obese rats for 3 weeks. By recording body weight (BW) and other measures, we identified the effective dose of celastrol for obesity treatment. Feces were collected to perform 16S rRNA sequencing, and hypothalami were extracted for transcriptome sequencing. We then treated leptin knockout rats with celastrol and explored the changes in energy metabolism. Male Institute of Cancer Research (ICR) mice were used to test the acute toxicity of celastrol. Results: We observed that celastrol reduced BW and promoted energy expenditure at a dose of 500 µg/kg BW but that food intake was not changed after administration. The diversity of the gut microbiota was improved, with an increased ratio of Bacteroidetes to Firmicutes, and the gut microbiota played an important role in the anti-obesity effects of celastrol. Hypothalamic transcriptome analysis showed a significant enrichment of the leptin signaling pathway, and we found that celastrol significantly enhanced energy expenditure, which was mediated by the leptin signaling pathway. Acute lethal toxicity of celastrol was not observed at doses ranging from 0 to 62.5 mg/kg BW. Conclusion: Our study revealed that celastrol decreased the BW of obese rats by enhancing energy expenditure but not by suppressing food intake and that this effect was mediated by the improvement of the gut microbiota and the activation of the hypothalamic leptin signaling pathway.

Increased risk of gestational diabetes mellitus in women with higher prepregnancy ambient PM2.5 exposure.

BACKGROUND: Air pollution is a serious environmental problem in China. This study was designed to investigate whether exposure to particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM2.5) before pregnancy is associated with gestational diabetes mellitus (GDM) and fasting glucose in China. METHODS: We recruited subjects and collected clinical data from the Nanjing Maternity and Child Health Care Hospital from July 2016 to October 2017. A series of validated land-use regression (LUR) models were built to assess individual exposure to PM2.5 in a 1 × 1 km area at both work and home addresses following a time-weighted pattern. Multiple linear regression and logistic regression analyses were performed to examine the association between PM2.5 exposure and GDM and fasting glucose. RESULTS: In total, 11,639 of 16,995 women were included in the final analysis. Among the 11,639 women, 2776 (23.85%) had GDM. Individual exposure to PM2.5 within three months before pregnancy ranged from 21.58 to 85.92 µg/m3. Positive associations were observed among the interquartile ranges (IQRs) of exposure to PM2.5 within three months before pregnancy and GDM (OR = 2.61, 95% CI: 1.40-4.93, p < .01) as well as fasting glucose levels (ß = 0.57, 95% CI: 0.45-0.68, p < .01). The diabetogenic effects of PM2.5 gradually increased from the first month before pregnancy, peaked in the second month and then gradually decreased until the third month when the week-specific exposure were analyzed to identify the sensitive time window. CONCLUSION: Our study confirmed that higher exposure to PM2.5 within three months before pregnancy is significantly associated with increased risk of GDM and elevated fasting glucose levels, reflecting the importance of preconceptional environmental exposure in the development of maternal GDM.

Prenatal exposure to glufosinate ammonium disturbs gut microbiome and induces behavioral abnormalities in mice.

Glufosinate ammonium (GLA) is a widely used organophosphate herbicide, which could be commonly detected in body fluids of both pregnant women and newborns. Existing evidences indicate that GLA has reproductive toxicity, while data concerning the effects of prenatal GLA exposure on neurodevelopment is rather limited. Here we employed a mouse model exposed to GLA prenatally. Reduced locomotor activity, impaired memory formation and autism-like behaviors were observed in the treatment group. Marked alteration in gut microbiome of the treatment offspring mice could be found at 4th week, and seemed to recover over time. Fecal metabolomics analysis indicated remarkable changes in microbiome-related metabolism in the treatment group, which could be the cause of behavioral abnormality in mice. Present study suggested that prenatal exposure to GLA disturbed gut microbiome and metabolism, and thereby induced behavioral abnormalities in mice.

Glycylglycine plays critical roles in the proliferation of spermatogonial stem cells.

Glial cell line­derived neurotrophic factor (GDNF) is critical for the proliferation of spermatogonial stem cells (SSCs), but the underlying mechanisms remain poorly understood. In this study, an unbiased metabolomic analysis was performed to examine the metabolic modifications in SSCs following GDNF deprivation, and 11 metabolites were observed to decrease while three increased. Of the 11 decreased metabolites identified, glycylglycine was observed to significantly rescue the proliferation of the impaired SSCs, while no such effect was observed by adding sorbitol. However, the expression of self­renewal genes, including B­cell CLL/lymphoma 6 member B, ETS variant 5, GDNF family receptor α1 and early growth response protein 4 remained unaltered following glycylglycine treatment. This finding suggests that although glycylglycine serves an important role in the proliferation of SSCs, it is not required for the self­renewal of SSCs.

Association between exposure to a mixture of phenols, pesticides, and phthalates and obesity: Comparison of three statistical models.

BACKGROUND: The evaluation of the chemical impact on human health is usually constrained to the analysis of the health effects of exposure to a single chemical or a group of similar chemicals at one time. The effects of chemical mixtures are seldom analyzed. In this study, we applied three statistical models to assess the association between the exposure to a mixture of seven xenobiotics (three phthalate metabolites, two phenols, and two pesticides) and obesity. METHODS: Urinary levels of environmental phenols, pesticides, and phthalate metabolites were measured in adults who participated in the U.S.-based National Health and Nutrition Examination Survey (NHANES) from 2013 to 2014. Body examination was conducted to determine obesity. We fitted multivariable models, using generalized linear (here both logistic and linear) regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models to estimate the association between chemical exposures and obesity. RESULTS: Of 1269 individuals included in our final analysis, 38.5% had general obesity and 58.0% had abdominal obesity. In the logistic regression model established for each single chemical, bisphenol S (BPS), mono (carboxyoctyl) phthalate (MCOP), and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP) were associated with both general and abdominal obesity (fourth vs. first quartile). In linear regression, MCOP was associated with BMI and waist circumference. In WQS regression analysis, the WQS index was significantly associated with both general obesity (OR = 1.63, 95% CI: 1.21-2.20) and abdominal obesity (OR = 1.66, 95% CI: 1.18-2.34). MCOP, bisphenol A (BPA), bisphenol S (BPS), and mono ethyl phthalate (MEP) were the most heavily weighing chemicals. In BKMR analysis, the overall effect of mixture was significantly associated with general obesity when all the chemicals were at their 60th percentile or above it, compared to all of them at their 50th percentile. MCOP, BPA, and BPS showed positive trends. By contrast, MECPP showed a flat and modest inverse trend. CONCLUSION: When comparing results from these three models, MCOP, BPA, and BPS were identified as the most important factors associated with obesity. We recommend estimating the joint effects of chemical mixtures by applying diverse statistical methods and interpreting their results together, considering their advantages and disadvantages.

Transcriptome and DNA Methylome Dynamics during Triclosan-Induced Cardiomyocyte Differentiation Toxicity.

Cardiac development is a dynamic process and sensitive to environmental chemicals. Triclosan is widely used as an antibacterial agent and reported to transport across the placenta and affect embryonic development. Here, we used human embryonic stem cell- (hESC-) derived cardiomyocytes (CMs) to determine the effects of TCS exposure on cardiac development. After TCS treatment, the differentiation process was significantly blocked and spontaneous beating rates of CMs were also decreased. Transcriptome analysis showed the dysregulation of genes involved in cardiogenesis, including GATA4 and TNNT2. Additionally, DNA methylation was also altered by TCS exposure, especially in those regions with GATA motif enrichment. These alterations of transcriptome and DNA methylation were all associated with signaling pathways integral to heart development. Our findings indicate that TCS exposure might cause cardiomyocyte differentiation toxicity and provide the new insights into how environmental factors regulate DNA methylation and gene expressions during heart development.