The progestin levonorgestrel affects sex differentiation in zebrafish at environmentally relevant concentrations

Synthetic progestins have become widespread environmental contaminants and may cause adverse effects on fish. In the present study, we investigated the effects of levonorgestrel (LNG) on sex differentiation in zebrafish (Danio rerio). Embryos were exposed to LNG at environmentally relevant concentrations (0, 1, 10, 33, and 100 ng/L) and allowed to develop until sexual maturity. Histological examination at 63 days post fertilization (dpf) caused complete sex reversal and 100% males were observed in the 10,33 and 100 ng/L treatments; gross morphological and histological examination of gonads at 142 dpf further confirmed 100% males at these exposure concentrations. The results indicate androgenic activity of LNG, and masculinization during zebrafish gonadal differentiation. The mRNA expression levels of genes involved in fish sex differentiation and gonadal development were examined at 28 and 42 dpf. Down-regulation of the mRNA expression of aromatase (e.g., cyp19a1 a, cyp19a1b), the forkhead transcription factor gene L2 (foxl2) and the Fushi tarazu factor-1d (nr5a1b) were observed. In contrast, transcription of the doublesex and mab-3-related transcription factor 1 (dmrt1) gene was up-regulated. Androgen receptor (ar) mRNA expression was significantly down-regulated at 28 and 42 dpf. Co-exposure to flutamide (an androgen antagonist) and LNG, led to a decrease in the sex inversion potency of LNG. Our study has demonstrated that environmentally relevant concentrations of LNG could alter sex differentiation and gonadal development in zebrafish. Our results also suggest a potentially high ecological risk of LNG to fish populations in LNG-contaminated aquatic environments. (C) 2015 Elsevier B.V. All rights reserved

GWAS Identifies Novel Susceptibility Loci on 6p21.32 and 21q21.3 for Hepatocellular Carcinoma in Chronic Hepatitis B Virus Carriers

Genome-wide association studies (GWAS) have recently identified KIF1B as susceptibility locus for hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC). To further identify novel susceptibility loci associated with HBV–related HCC and replicate the previously reported association, we performed a large three-stage GWAS in the Han Chinese population. 523,663 autosomal SNPs in 1,538 HBV–positive HCC patients and 1,465 chronic HBV carriers were genotyped for the discovery stage. Top candidate SNPs were genotyped in the initial validation samples of 2,112 HBV–positive HCC cases and 2,208 HBV carriers and then in the second validation samples of 1,021 cases and 1,491 HBV carriers. We discovered two novel associations at rs9272105 (HLA-DQA1/DRB1) on 6p21.32 (OR = 1.30, P = 1.13×$10^{−19}$) and rs455804 (GRIK1) on 21q21.3 (OR = 0.84, P = 1.86×$10^{−8}$), which were further replicated in the fourth independent sample of 1,298 cases and 1,026 controls (rs9272105: OR = 1.25, P = 1.71×$10^{−4}$; rs455804: OR = 0.84, P = 6.92×$10^{−3}$). We also revealed the associations of HLA-DRB1*0405 and 0901*0602, which could partially account for the association at rs9272105. The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV–related HCC, suggesting the involvement of glutamate signaling in the development of HBV–related HCC

Assessment of Water Quality Improvements Using the Hydrodynamic Simulation Approach in Regulated Cascade Reservoirs: A Case Study of Drinking Water Sources of Shenzhen, China

Water quality safety is of critical importance in environmental improvement, particularly with respect to drinking water resources worldwide. As the main drinking water sources in Shenzhen, China, the cascade reservoirs comprising the Shiyan, Tiegang, and Xili Reservoirs are highly regulated and have experienced water quality deterioration in recent years. In this study, a three-dimensional hydrodynamic and water quality model was established using the Environmental Fluid Dynamics Code (EFDC) for the cascade reservoirs. The relationships between water quality and improvement measures were quantified and the main pollution sources for individual reservoirs were identified. Results showed that the hydrodynamic and water quality model well captured the spatial and temporal variations of water level, the permanganate concentration index (CODMn), and total nitrogen (TN), with high resolution in the cascade reservoirs. The correlation coefficients between simulations and observations were close to 1.00 for water levels, and over 0.50 for CODMn and TN concentrations. The most effective methods for water quality improvement were the reduction of the runoff load for TN and transferred water load for CODMn in the Shiyan Reservoir, reduction of the transferred water load in the Tiegang Reservoir, and an increase in transfer water volume, especially in the flood season, in the Xili Reservoir. Internal pollution sources also played an important role in water pollution, and thus sedimentation should be cleaned up regularly. This study is expected to provide scientific support for drinking water source protection and promote the application of hydrodynamic model in water quality management

Endocrine disruption in Chinese rare minnow (Gobiocypris rarus) after long-term exposure to low environmental concentrations of progestin megestrol Check for acetate

Synthetic progestins are widely used pharmaceutical agents that have become common contaminants in the aquatic environment. The potential adverse effects of long-term exposure on aquatic wildlife, however, are not fully understood. The aim of this study was to investigate the endocrine disruption in Chinese rare minnow (Gobiocypris rarus) in response to megestrol acetate (MTA) exposure. Newly-hatched Chinese rare minnow larvae were exposed to MTA at a nominal concentration of either 1 ng/L (detected concentrations ranged from 0.18 to 0.93 ng/L) or 10 ng/L (detected concentrations ranged from 4.27 to 9.64 ng/L) for 6 months and the effects on growth, sex steroid hormones, gonadal histology, and steroidogenic genes expression were determined. After 6 months of exposure to a nominal concentration of 10 ng/L MTA, the body weight and condition factors were significantly increased in fish of both sexes. Exposure to a nominal concentration of 10 ng/L MTA significantly reduced plasma concentrations of estradiol and 11-ketotestosterone in female fish while also reducing testosterone and 11-ketotestosterone in male fish. Gonad histology revealed significantly reduced proportions of vitellogenic oocytes in female fish exposed to a nominal concentration of 10 ng/L MTA and induction of atretic follicles in female fish exposed to both nominal concentrations of MTA. The expression of cyp19a1a and cyp17a1 in the gonads was up-regulated in the ovaries while down-regulated in the testes. Our results indicate that MTA can induce endocrine disruption in Chinese rare minnow at the low concentrations found in contaminated environments. This indicates a potentially high ecological risk from MTA to fish populations in MTA-contaminated aquatic environments in China and may also in other regions.</p

Identification of significant gene and pathways involved in HBV-related hepatocellular carcinoma by bioinformatics analysis

Background Hepatocellular carcinoma (HCC) is a common malignant tumor affecting the digestive system and causes serious financial burden worldwide. Hepatitis B virus (HBV) is the main causative agent of HCC in China. The present study aimed to investigate the potential mechanisms underlying HBV-related HCC and to identify core biomarkers by integrated bioinformatics analyses. Methods In the present study, HBV-related HCC GSE19665, GSE55092, GSE94660 and GSE121248 expression profiles were downloaded from the Gene Expression Omnibus database. These databases contain data for 299 samples, including 145 HBV-related HCC tissues and 154 non-cancerous tissues (from patients with chronic hepatitis B). The differentially expressed genes (DEGs) from each dataset were integrated and analyzed using the RobustRankAggreg (RRA) method and R software, and the integrated DEGs were identified. Subsequently, the gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the DAVID online tool, and the protein–protein interaction (PPI) network was constructed using STRING and visualized using Cytoscape software. Finally, hub genes were identified, and the cBioPortal online platform was used to analyze the association between the expression of hub genes and prognosis in HCC. Results First, 341 DEGs (117 upregulated and 224 downregulated) were identified from the four datasets. Next, GO analysis showed that the upregulated genes were mainly involved in cell cycle, mitotic spindle, and adenosine triphosphate binding. The majority of the downregulated genes were involved in oxidation reduction, extracellular region, and electron carrier activity. Signaling pathway analysis showed that the integrated DEGs shared common pathways in retinol metabolism, drug metabolism, tryptophan metabolism, caffeine metabolism, and metabolism of xenobiotics by cytochrome P450. The integrated DEG PPI network complex comprised 288 nodes, and two important modules with high degree were detected using the MCODE plug-in. The top ten hub genes identified from the PPI network were SHCBP1, FOXM1, KIF4A, ANLN, KIF15, KIF18A, FANCI, NEK2, ECT2, and RAD51AP1. Finally, survival analysis revealed that patients with HCC showing altered ANLN and KIF18A expression profiles showed worse disease-free survival. Nonetheless, patients with FOXM1, NEK2, RAD51AP1, ANLN, and KIF18A alterations showed worse overall survival. Conclusions The present study identified key genes and pathways involved in HBV-related HCC, which improved our understanding of the mechanisms underlying the development and recurrence of HCC and identified candidate targets for the diagnosis and treatment of HBV-related HCC

Research Progress of the Gut Microbiome in Hybrid Fish

Fish, including hybrid species, are essential components of aquaculture, and the gut microbiome plays a vital role in fish growth, behavior, digestion, and immune health. The gut microbiome can be affected by various internal and/or external factors, such as host development, diet, and environment. We reviewed the effects of diet and dietary supplements on intestinal microorganisms in hybrid fish and the difference in the gut microbiome between the hybrid and their hybrids that originate. Then, we summarized the role of the gut microbiome in the speciation and ecological invasion of hybrid fish. Finally, we discussed possible future studies on the gut microbiome in hybrid fish, including the potential interaction with environmental microbiomes, the effects of the gut microbiome on population expansion, and fish conservation and management

Parental co-exposure to bisphenol A and nano-TiO2 causes thyroid endocrine disruption and developmental neurotoxicity in zebrafish offspring

The coexistence of organic toxicants and nanoparticles in the environment influences pollutant bioavailability and toxicity. Using chronic co-exposure to an adult zebrafish model, this study investigated the transfer kinetics and transgenerational effects of bisphenol A (BPA) and titanium dioxide nanoparticles (n-TiO2) exposure in F1 offspring. When single and combined exposure to BPA (0, 2, and 20 mu g/L) and n-TiO2 (100 mu g/L) were compared, combined exposure was found to reciprocally facilitate bioaccumulation in adult fish while enhancing maternal transfer to offspring. Thyroid endocrine disruption and developmental neuroloxiciLy were observed in larval offspring by parental exposure to BPA alone or in combination with n-TiO2. Exposure to 20 mu g/L BPA significantly decreased the thyroxine (T4) concentration in adult plasma, leading to less transfer info the eggs. The presence of 20 mu g/L BPA with n-TiO2 further decreased the level of T4 compared lo BPA exposure alone. Additionally, offspring larvae derived from exposed parents exhibited lethargic swimming behavior. Overall, this study examined the interactions of BPA and n-TiO2 with regard lo their bioaccumulation, maternal transfer, and developmental effects, which highlighted that co-exposure dynamics are important and need to be considered for accurate environmental risk assessment. (C) 2018 Elsevier B.V. All rights reserved.</p