Specific effects of prenatal DEHP exposure on neuroendocrine gene expression in the developing hypothalamus of male rats.

Endocrine disrupting chemicals may disrupt developing neuroendocrine systems, especially when the exposure occurs during a critical period. This study aimed to investigate whether prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP), a major component of plasticizers used worldwide, disrupted the development of a network of genes important for neuroendocrine function in male rats. Pregnant rats were treated with corn oil (vehicle control), 2, 10 or 50 mg/kg DEHP by gavage from gestational day 14 to 19. The neuroendocrine gene expressions were quantified using a 48-gene Taqman qPCR array in the whole hypothalamus of neonatal rats (postnatal day 1) and in the anteroventral periventricular nucleus (AVPV), medial preoptic nucleus (MPN) and arcuate nucleus (ARC) of adult rats (postnatal day 70). Immunofluorescent signals of ERα and CYP19 were detected using the confocal microscopy in adult AVPV, MPN and ARC. The results showed that prenatal DEHP exposure perturbed somatic and reproductive development of offspring. Eleven genes were down-regulated in neonatal hypothalamus and showed non-monotonic dose-response relationships, that the 10 mg/kg DEHP dosage was associated with the greatest number of gene expression changes. Different from this, 14 genes were altered in adult AVPV, MPN and ARC and most of alterations were found in the 50 mg/kg DEHP group. Also, 50 mg/kg DEHP reduced ERα expression in the ARC, but no alterations were observed in CYP19 expression. These results indicated that prenatal DEHP exposure may perturb hypothalamic gene programming and the influences are permanent. The effects showed dependence on developmental stages and nuclei region.

Application prospective of nanoprobes with MRI and FI dual-modality imaging on breast cancer stem cells in tumor.

Breast cancer (BC) is a serious disease to threat lives of women. Numerous studies have proved that BC originates from cancer stem cells (CSCs). But at present, no one approach can quickly and simply identify breast cancer stem cells (BCSCs) in solid tumor. Nanotechnology is probably able to realize this goal. But in study process, scientists find it seems that nanomaterials with one modality, such as magnetic resonance imaging (MRI) or fluorescence imaging (FI), have their own advantages and drawbacks. They cannot meet practical requirements in clinic. The nanoprobe combined MRI with FI modality is a promising tool to accurately detect desired cells with low amount in tissue. In this work, we briefly describe the MRI and FI development history, analyze advantages and disadvantages of nanomaterials with single modality in cancer cell detection. Then the application development of nanomaterials with dual-modality in cancer field is discussed. Finally, the obstacles and prospective of dual-modal nanoparticles in detection field of BCSCs are also pointed out in order to speed up clinical applications of nanoprobes.

Expression of Vesicular Glutamate Transporter 2 (vGluT2) on Large Dense-Core Vesicles within GnRH Neuroterminals of Aging Female Rats.

The pulsatile release of GnRH is crucial for normal reproductive physiology across the life cycle, a process that is regulated by hypothalamic neurotransmitters. GnRH terminals co-express the vesicular glutamate transporter 2 (vGluT2) as a marker of a glutamatergic phenotype. The current study sought to elucidate the relationship between glutamate and GnRH nerve terminals in the median eminence--the site of GnRH release into the portal capillary vasculature. We also determined whether this co-expression may change during reproductive senescence, and if steroid hormones, which affect responsiveness of GnRH neurons to glutamate, may alter the co-expression pattern. Female Sprague-Dawley rats were ovariectomized at young adult, middle-aged and old ages (~4, 11, and 22 months, respectively) and treated four weeks later with sequential vehicle + vehicle (VEH + VEH), estradiol + vehicle (E2 + VEH), or estradiol + progesterone (E2+P4). Rats were perfused 24 hours after the second hormone treatment. Confocal microscopy was used to determine colocalization of GnRH and vGluT2 immunofluorescence in the median eminence. Post-embedding immunogold labeling of GnRH and vGluT2, and a serial electron microscopy (EM) technique were used to determine the cellular interaction between GnRH terminals and glutamate signaling. Confocal analysis showed that GnRH and vGluT2 immunofluorescent puncta were extensively colocalized in the median eminence and that their density declined with age but was unaffected by short-term hormone treatment. EM results showed that vGluT2 immunoreactivity was extensively associated with large dense-core vesicles, suggesting a unique glutamatergic signaling pathway in GnRH terminals. Our results provide novel subcellular information about the intimate relationship between GnRH terminals and glutamate in the median eminence.

A comprehensive assessment of human exposure to phthalates from environmental media and food in Tianjin, China.

A total of 448 samples including foodstuffs (rice, steamed bun, vegetables, meat, poultry, fish, milk and fruits), ambient PM10, drinking water, soil, indoor PM10 and indoor dust samples from Tianjin were obtained to determine the distribution of six priority phthalates (PAEs) and assess the human exposure to them. The results indicated that DBP and DEHP were the most frequently detected PAEs in these samples. The concentrations of PAEs in environmental media were higher than those in food. We estimated the daily intake (DI) of PAEs via ingestion, inhalation and dermal absorption from five sources (food, water, air, dust and soil). Dietary intake was the main exposure source to DEP, BBP, DEHP and DOP, whereas water ingestion/absorption was the major source of exposure to DBP, DEHP and DOP. Although food and water were the overwhelmingly predominant sources of PAEs intake by Tianjin population, contaminated air was another important source of DMP, DEP and DBP contributing to up to 45% of the exposure. The results of this study will help in understanding the major pathways of human exposure to PAEs. These findings also suggest that human exposure to phthalate esters via the environment should not be overlooked.

[Study on the association between maternal urinary phthalate metabolites and testicular steroid hormones in the cord blood in a Chinese population].

OBJECTIVE: The purposes of our study were to investigate the association between maternal urinary phthalate metabolites and the levels of inhibin B (INHB) and insulin-like factor 3 (INSL3) in the cord blood in a Chinese pregnant population. METHODS: Maternal urine samples in the third trimester of pregnancy of 69 participants were collected and stored, and the samples of cord blood (10 ml) were collected at delivery between June 2011 and September 2012 in a comprehensive hospital of gynecology and obstetrics in Tianjin, China.Four phthalate metabolites, monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), and mono-2-ethylhexyl phthalate (MEHP) were measured in the urine samples using liquid chromatography-tandem mass spectrometry. The levels of INHB, INSL3 in the cord blood were tested by ELISA. Associations of phthalate exposure with INHB and INSL3 levels were determined by spearman correlation and multiple regression model analysis. RESULTS: The median concentrations of observed metabolites in descending order were 49.74 µg/L for MMP, 24.96 µg/L for MEHP, 19.52 µg/L for MEP and 17.73 µg/L for MBP. The median concentrations of INHB and INSL3 were 89.09 and 106.21 ng/L.Significant negative associations between INHB and MMP(ß' = -0.252), MEP(ß' = -0.363) or the sum value (∑PAEs) (ß' = -0.346) were found by the multiple regression model analysis. For INSL3, only the sum value (ß' = -0.313) was inversely significantly associated with the levels of INSL3 in the cord blood. CONCLUSIONS: Maternal urinary phthalate metabolites were associated with INHB and INSL3 in the cord blood in a Chinese population.

Long-term exposure to high particulate matter pollution and cardiovascular mortality: a 12-year cohort study in four cities in northern China.

Epidemiologic studies have demonstrated that long-term exposure to relatively low levels of particulate air pollution is associated with adverse cardiovascular outcomes in Europe and North America. However, few studies have assessed the association with high level air pollutants. We aimed to assess the cardiovascular effects of long-term exposure to high level concentrations of inhalable particulate and to identify the characteristics of the Chinese population that are susceptible to the health effects. A retrospective cohort, containing 39,054 subjects from four cities in northern China, was followed for mortality of all cause and specific cardiovascular diseases from 1998 to 2009. Information on concentrations of PM10 (particulate matter<10 µm in aerodynamic diameter) was collected from the local Environmental Monitoring Centers. The estimated exposure for the study participants was the mean concentration of PM10 over their surviving years during the cohort period. Relative risk values were obtained using Cox proportional hazards regression models after adjusting for potential confounding factors. For each 10 µg/m(3) increase in PM10, the relative risk ratios (RRs) of all-cause mortality, cardiovascular disease mortality, ischemic heart disease mortality, heart failure disease mortality, and cerebrovascular disease mortality were 1.24 (95% CI, 1.22-1.27), 1.23 (95% CI, 1.19-1.26), 1.37 (95% CI, 1.28-1.47), 1.11(95% CI, 1.05-1.17), and 1.23(95% CI:1.18-1.28), respectively. Results from stratified analyses suggest that the effects of PM10 on cardiovascular mortality were more pronounced in males, smokers and people with a higher socioeconomic status. Long-term exposure to PM10 increases mortality from cardiovascular disease, especially from ischemic heart disease and this association seemed to be modified by other factors. Further research that focuses on exploring dose-response relationship and inter-population comparisons is warranted.

Effects of di(n-butyl) and monobutyl phthalate on steroidogenesis pathways in the murine Leydig tumor cell line MLTC-1.

Di(n-butyl) phthalate (DBP) and its active metabolite monobutyl phthalate (MBP) have been shown to disrupt reproductive organ growth. The objective of this study was to evaluate the effects of DBP/MBP on steroidogenesis in the murine Leydig tumor cell line MLTC-1 in vitro. MLTC-1 cells were incubated with various concentrations of DBP (100, 1, 0.01, and 0µmol/l in DMSO) and MBP (1000, 10, 0.1, and 0µmol/l in DMSO) for 24h. Testosterone secretion was stimulated at the lowest doses and inhibited at higher treatment doses of DBP and MBP. The mRNA levels of the side-chain cleavage enzyme (P450scc), cytochrome p450c17 (P450c17) and 3ß-hydroxy-steroid dehydrogenase (3ßHSD) were significantly reduced in the phthalate-exposed groups, whereas, the transcription and translation of insulin-like hormone 3 (INSL3) was affected by DBP and MBP. Alterations of the steroidogenic enzymes and INSL3 in MLTC-1 cells may be involved in the biphasic effects of DBP/MBP on androgen production.

Diversities of phthalate esters in suburban agricultural soils and wasteland soil appeared with urbanization in China.

The distribution of six priority phthalic acid esters (PAEs) in suburban farmland, vegetable, orchard and wasteland soils of Tianjin were obtained with gas chromatography-mass spectrometer analysis in 2009. Results showed that total PAEs varied from 0.05 to 10.4 µg g(-1), with the median value as 0.32 µg g(-1). Di-(2-ethylhexyl) phthalate and di-n-butyl phthalate are most abundant species. PAEs concentrations for the four types of soils exhibited decreasing order as vegetable soil > wasteland soil > farmland soil > orchard soil. PAEs exhibited elevated levels in more developed regions when compared with other studies. The agricultural plastic film could elevate the PAEs contents in soils. Principal component analysis indicated the emission from cosmetics and personal care products and plasticizers were important sources for PAEs in suburban soils in Tianjin. The higher PAEs contents in wasteland soils from suburban area should be paid more attention owing to large amounts of solid wastes appeared with the ongoing urbanization.