Rui Hua

Chronic exposure to mono‐(2‐ethylhexyl)‐phthalate causes endocrine disruption and reproductive dysfunction in zebrafish

Phthalic acid esters are frequently detected in aquatic environments. In the present study, zebrafish were exposed to low concentrations (0 µg/L, 0.46 µg/L, 4.0 µg/L, and 37.5 µg/L) of mono-(2-ethylhexyl) phthalate (MEHP) for 81 d, and the effects on reproduction, gamete quality, plasma vitellogenin (VTG), sex steroids, and transcriptional profiles of key genes involved in steroidogenesis were investigated. The results demonstrated that egg production and sperm quality were decreased after exposure to MEHP, which also resulted in reduced egg diameter and eggshell as well as decreased egg protein content. Significant inductions in plasma testosterone and 17β-estradiol (E2) were observed in females, which might have resulted from up-regulation of CYP19a and 17β-HSD gene transcription in the ovary. A significant increase in plasma E2 along with a decrease in plasma 11-keto testosterone was also observed in males, which was accompanied by up-regulation of CYP19a and inhibition of CYP11b transcription in the testis. In addition, plasma vitellogenin levels were significantly increased after MEHP exposure in both sexes. Moreover, continuous MEHP exposure in the F1 embryos resulted in worse hatching rates and increased malformation rates compared with embryos without MEHP exposure. Taken together, these results demonstrate that MEHP has the potential to cause reproductive dysfunction and impair the development of offspring. However, it should be noted that most of the significant effects were observed at higher concentrations, and MEHP at typically measured concentrations may not have major effects on fish reproduction and development. Environ Toxicol Chem 2016;35:2117-2124.

Urinary triclosan concentrations and early outcomes of in vitro fertilization-embryo transfer

Triclosan (TCS) exists ubiquitously in the environment. Several in vitro and in vivo studies have demonstrated that TCS exerts endocrine disruptive effects on reproduction, but data from human populations are limited and conflicting. The objective of our study was to investigate whether high urinary TCS concentration is adversely associated with early reproductive outcomes in women undergoing in vitro fertilization-embryo transfer (IVF-ET). This prospective cohort study was conducted from September 2015 to June 2016, including 156 infertile women undergoing their first IVF-ET cycle. Two spot urine samples were collected prior to oocyte retrieval for TCS detection using solid-phase extraction (SPE) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Linear regression model and binary logistic regression model were used to evaluate the association between urinary TCS concentrations and IVF outcomes. The intake of aquaculture food may have positive influences on urinary TCS concentrations. After adjustment for age, body mass index (BMI), baseline follicle-stimulating hormone (FSH), antral follicle count (AFC) and smoking status, a significant decrease of top quality embryo formation and implantation rate was observed in patients with urinary TCS concentration greater than or equal to the median level (0.045 μmol/mol Cr). We concluded that TCS exposure may exert negative effects during early stages of human reproduction.

Immunotherapy against metastatic bladder cancer by combined administration of granulocyte macrophage‐colony stimulating factor and interleukin‐2 surface modified MB49 bladder cancer stem cells vaccine

In previous studies, it has been shown that the granulocyte macrophage‐colony stimulating factor (GM‐CSF) or interleukin‐2 (IL‐2) surface modified MB49 bladder cancer stem cells (MCSCs) vaccine could induce a specific antitumor immunity and against bladder cancer in mice model respectively. However, whether combined administration of GM‐CSF and IL‐2 could produce specific immune responses to cancer stem cells (CSCs) was uncertain. MCSCs were established and characterized. GM‐CSF and IL‐2 MCSCs vaccines were prepared and bioactivity was evaluated. The therapeutic, protective, specific, and memorial immune response animal experiments were designed. Tumor‐specific cytotoxic T lymphocytes assay, enzyme linked immunosorbent assay, flow cytometry assay were performed to indentify whether vaccine caused an antitumor immunity. Streptavidin (SA)‐GM‐CSF and SA‐IL‐2 MCSCs vaccines were prepared successfully. Such vaccines inhibited the volume of tumor and prolonged the survival of the mice in animal experiments. The express of IgG or IFN‐c, the portion of dendritic cells, CD8+ and CD4+ T cells were highest in the combined vaccines group than the SA‐GM‐CSF vaccine group, the SA‐IL‐2 vaccine group, the MCSCs group and the PBS group. The combined of GM‐CSF and IL‐2 vaccines could induce better antitumor immunity than a vaccine alone.

Polycyclic aromatic hydrocarbons exposure and early miscarriage in women undergoing in vitro fertilization-embryo transfer

Abstract Various factors have been reported to be associated with early miscarriages, including microbial infection, chemical toxicity, maternal disorders and genetic abnormalities. In the present study, a prospective cohort study was conducted to investigate whether urinary concentrations of hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) were associated with early pregnancy loss in women undergoing in vitro fertilization-embryo transfer (IVF-ET). Risk of spontaneous pregnancy loss in patients exposed to PAHs was analysed using 40 patients who had experienced early pregnancy loss compared to 40 who had normal live births. Single spot morning urine samples were collected from each patient 30 days after embryo transfer when clinical pregnancy was confirmed and ten urinary OH-PAHs were measured. After adjustment for age and BMI using a Log Binomial Model, only 2 + 3-PHE was found to be associated positively with early miscarriage. Using Receiver Operating Characteristic (ROC) curve analysis, the Area Under the Curve (AUC) was 0.78 (p＜0.001), suggesting that 2 + 3-PHE might provide a potential biomarker to predict the miscarriage risk in patients exposed to high level of PAHs.

Advanced oxidation protein products from the follicular microenvironment and their role in infertile women with endometriosis

Endometriosis (EM) is associated with oxidative stress. Advanced oxidation protein products (AOPPs) are novel markers of oxidative stress, which serve an important role as an inflammatory mediator in various chronic diseases. In order to examine the role of AOPPs in infertile women with EM, the present study analyzed the levels of AOPPs, estradiol (E2) and progesterone (P4) in the follicular fluid (FF) of 89 women with or without EM undergoing in vitro fertilization (IVF). The AOPP concentration in the FF of the EM group was significantly higher when compared with that of the control group (51.5±22.4 vs. 41.8±18.3 µmol/l; P<0.05). However, the FF P4 levels and blastocyst rate were significantly lower in the EM group compared with the control group (P4:1,249.6±465.4 vs. 1,752.7±565.4 ng/ml, P<0.05; blastocyst rate: 0.511±0.322 vs. 0.662±0.278; P<0.05). The AOPP concentration and P4 level in the FF presented a significant negative correlation in the EM and control groups, as well as in the total cohort of patients (EM group: r=-0.406, P=0.006; control group: r=-0.315, P=0.035; total: r=-0.421, P<0.001). In addition, there was a significant negative correlation between the FF AOPP concentrations and blastocyst rate in the EM group and in the total cohort (EM group: r=-0.376, P=0.012; total: r=-0.367, P<0.001). In conclusion, these results suggested that AOPPs may be a potentially effective marker for predicting the oocyte quality and outcomes of IVF in infertile women with EM.