Search

Zearalenone (ZEA) is a non-steroidal estrogenic mycotoxin produced by Fusarium species. The toxicity of ZEA has been evaluated for reproductive and developmental effects; however, there is little evidence about its acute toxicity or general immunotoxicity. In the present study, immune regulatory functions were investigated in mice that had been exposed to ZEA (5 or 20 mg/kg BW) daily for 14 days. Results showed that sub-populations of CD4 + , CD8 + and CD11c + cells in the spleen and CD4 + , CD8 + and F4/80 + cells in the mesenteric lymph nodes (MLN) of ZEA (20 mg/kg)-exposed hosts were decreased compared to those in the control mice. However, CD19 + and CD11c + cells were increased in the MLN of the ZEA mice and CD4 + CD25 + Foxp3 + cells were decreased in the spleen and MLN. There were differential changes in the immune cell populations of the small intestine of the ZEA mice as well, depending on small intestine location. In ex vivo experiments, ZEA treatments resulted in increased proliferative capacities of mitogen-induced splenocytes and MLN cells; such changes were paralleled by significant increases in interferon (IFN)-γ production. With regard to serum isotypes, IgM levels were decreased and IgE levels were increased in the 20 mg/kg ZEA-treated mice. Mucosal IgA levels were decreased in the duodenum and vagina of these hosts. Serum analyzes also revealed that tumor necrosis factor (TNF)-α levels were decreased and interleukin (IL)-6 levels increased as a result of ZEA exposures. ZEA treatment also led to increased apoptosis in the spleen and Peyer's patches; these changes were associated with changes in the ratios of Bax:Bcl-2. Following priming with different TLR ligands, ZEA exposure led to differentially modulated TLR signaling and variable production of pro- and anti-inflammatory cytokines in RAW 264.7 macrophage cells. Taken together, these results indicated that ZEA could alter the normal expression/function of different immune system components and this would likely lead to immunomodulation in situ.

Close relationship between polycystic ovary syndrome (PCOS) and bisphenol A (BPA) has drawn much attention in recent years, while the underlying mechanisms are poorly understood. In our study, we aim to detect BPA concentration in the follicular fluid and investigate its effect on estradiol synthesis in human granulosa cells from PCOS and non-PCOS patients. Follicular fluid and granulosa cells were collected from women who underwent controlled ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection. BPA concentration in the follicular fluid from PCOS patients (440.50 ± 63.70 pg/ml) was significantly higher than that from non-PCOS patients (338.00 ± 57.88 pg/ml). Expression of aromatase and estradiol synthesis in cultured granulosa cells was examined after treatment with BPA from 0.01 to 1 μM for 24 h. Expression of aromatase and estradiol synthesis was downregulated by BPA in a dose-dependent manner in PCOS, but no effect was observed in granulosa cells from non-PCOS patients. These findings provide evidence that increased BPA concentration in the follicular fluid of PCOS patients may play an important role in its pathogenesis by attenuating the expression of aromatase in granulosa cells.

Zearalenone (ZEN) has caused significant economic effects on swine production in China. There is growing concern that exposure to ZEN during pregnancy affects the health of the offspring due to changes in the development of the immune system. To assess the risks associated with maternal ZEN exposure, several immunological parameters were assessed in pregnant sows and their offspring. The main aim of the study was to determine if modified hallosite nanotubes (MHNTs) can be used to protect pigs against the adverse effects of ZEN. Eighteen pregnant sows (second parity Yorkshire sows) were randomly divided into three treatment groups: (1) basal diet (control group); (2) contaminated grain (instead of 50% mouldy corn); and (3) contaminated grain (instead of 50% mouldy corn) + 1% MHNTs. The pregnant sows were fed the different treated diets from days 35 to 70 of gestation. Dietary ZEN exposure decreased the organ coefficient and the mRNA expression levels of IFN-γ, TNF-α, and IL-10, and increased ZEN residues and IL-4 mRNA expression in the spleen of pregnant sows and neonatal piglets. Decreases in the serum IgA and IgG levels were observed in the pregnant sows. Maternal ZEN exposure decreased the organ coefficient and the mRNA expression levels of IFN-γ and IL-10, and increased IL-4 mRNA expression in the spleen of weaning piglets. Exposure to ZEN during pregnancy decreased the level of serum IgG in the weaning piglets. Maternal exposure to ZEN induced histopathological damage and oxidative stress in the spleens of pregnant sows and their piglets. The addition of MHNTs to ZEN-contaminated diets can mitigate the negative effects induced by ZEN in the swine.

Adverse living and nutritional conditions in utero and in early infancy may influence the risk of diseases in adult life, because fetal growth seems determined by interactions between the environment and the fetal genome and these interactions may determine the risk of postnatal disease and the capacity to react to and cope with the postnatal environment. It has been proven that massive fetal exposure to toxic agents causes an increased incidence of negative outcomes in pregnant women; of particular interest is the association between in utero exposure to toxic agents and the occurrence of endometriosis. There is evidence that exposure to dioxins can facilitate short-term survival of endometrial implants in non-human primates, but there is no solid evidence that it may lead to endometriosis in humans. In the case of diethylstilbestrol, an increased risk of developing endometriosis seems well established, although the mechanisms through which diethylstilbestrol can modify endometrial physiology remain uncertain. Finally, evidence that environmental and specific dietary factors may play a role in increasing the incidence of endometriosis and other pathologic conditions has accumulated over the years. Although the hypothesis may be valid, the most recent investigations have failed to find specific, significant correlations.

Processed and packaged food items as well as ready-to-eat snacks are neglected and poorly characterised sources of human exposure to endocrine-disrupting chemicals (EDCs). In this study we investigated the presence of xenoestrogens in commercially processed and packaged Finnish foods, arising from substances deliberately added or inadvertently contaminating the food, substances formed as a result of food processing, or substances leaching from food packaging materials. Samples were obtained in three separate batches of equivalent products from both a supermarket and a local representative of a global chain of hamburger restaurants and extracted by a solid-phase extraction method. Their endocrine-disrupting potential was determined by yeast bioluminescent assay, using two recombinant yeast strains Saccharomyces cerevisiae BMAEREluc/ERα and S. cerevisiae BMA64/luc. In this test system, the majority of samples (both foodstuffs and wrappers) analysed proved negative. However, all batches of industrially prepared hamburgers (but not those obtained from a hamburger restaurant) as well as pepper salami significantly induced luciferase activity in the BMAEREluc/ERα yeast strain indicating the presence of xenoestrogens, with estradiol equivalents of these products ranging from 0.2 to 443 pg g(-1). All three products contained soy-based ingredients, which apparently accounted for, or at least contributed to, their high estrogenic activity, since no signal in the assay was observed with extracts of the packaging material, while two different soy sauces tested yielded an intense signal (28 and 54 pg ml(-1) estradiol-equivalent). These findings imply that by and large chemicals arising in the processing or packaging of foodstuffs in Finland constitute an insignificant source of xenoestrogens to consumers. However, soy-derived ingredients in certain food items might render the entire products highly estrogenic. The estrogenic activity of soy is attributed to isoflavones whose health effects - though widely considered beneficial - are controversial. As hamburgers are a popular type of food among children, the findings are noteworthy and possibly of concern.

Background: Endocrine disrupters have been shown to affect the male and female reproductive systems and to alter potential fertility., Objectives: This study was conducted to evaluate the effect of a continuous-release pellet containing 12 mg of zeranol for 30 days on the testes and the prostate gland of mature male rats., Results: Zeranol treatment induced significant decrease of the testes and the prostate gland weights which were associated with a remarkable atrophy of the testicular seminiferous tubules and prominent regression of the glandular compartment of the prostate gland. However, zeranol treatment increased the thickness of the periductal layer of stromal cells of the prostate gland from a thin layer that express intense immunostaining of SM-actin and mild vimentin to a thicker layer of cells that exhibited intense immunostaining for both SM-actin and vimentin., Conclusion: These findings suggest that zeranol-induced changes to the prostate gland could result from either a direct effect of zeranol on the prostate gland or an indirect effect by interfering with testosterone production through disruption of testicular function.

Background and Aim: The present study was conducted to determine the abilities of the living Lactobacillus plantarum MON03 (LP) cells, Tunisian montmorillonite clay and their composites to accumulate Zearalenone (ZEA) from a liquid medium and elucidate the preventive effect of their composite in ZEA-contaminated balb/c mice showing immunotoxicity disorders., Materials and Methods: In the in vitro study, LP (2 × 10(9) CFU/mL), TM (0.5 mg) and LP+TM were incubated with 50 µg mL(-1) ZEA for 0, 12 and 24 h. For the in vivo study, the composite MT+LP was evaluated also for possible protection regarding ZEA-immunotoxicity in Balb/c mice as a sensitive model., Results: Results indicated that TM and LP+TM had a high capacity of adsorbing ZEA 87.2 ± 2.1 and 94.2 ± 2.1%, respectively. However, LP alone able to remove only 78% after 24 h of incubation. The quantity of adsorbed ZEA by LP, TM and LP+TM were 39, 43,5 and 47 µg mL(-1) of PBS, respectively. The in vivo results indicated that mice orally exposed to ZEA- (40 mg/kg bw) for 2 weeks showed severe immunotoxicity typical of fusarotoxicosis regarding thymocytes and splenocytes cell viability count, IFN-γ, IL-12, TNF-α production and B-cell activation. Mice treated with LP and TM alone, and LP+MT in combination with ZEA were comparable to the control., Conclusion: Both LP and TM are safe by themselves and their composite succeeded to exert a potential prevention by counteracting ZEA-immunotoxicity and can be implicated in the biotechnology of ZEA removal in human food and animal feed.

Objectives: We explored whether in utero DES exposure has produced consistent findings with regard to an increased risk of psychiatric disorders., Methods: We reviewed systematically the epidemiological studies investigating a possible association between prenatal DES exposure and risk of psychiatric disorders., Results: We identified 10 relevant studies reporting the psychiatric outcome of offspring with a history of in utero DES exposure compared to a control group. We classified them into four categories: (1) a mail survey in a sample from a randomized double-blind controlled trial of prophylactic DES for first pregnancy in the early 1950s reported that depression and anxiety were twice as frequent in the exposed group compared to the placebo group; (2) five small clinical samples with inconclusive results; (3) two large cohorts of DES-exposed participants: the first study reported a higher lifetime history of weight loss related to anorexia nervosa whereas the second did not found any significant difference; (4) two subsamples from general population cohorts: the first study did not found any significant difference whereas the second reported that exposed women showed a higher rate of incident depression than non-exposed women., Conclusions: The role of prenatal exposure to DES as an environmental risk factor for psychiatric disorders requires more evidence before any conclusions can be drawn. If confirmed, several explanations could be proposed: gene × environment interaction and epigenetic mechanisms, although phenocopy and gene-environment aggregation are plausible.

This study reports the findings of a supplement marketed on the Internet for prostate problems. The supplement was orally taken by a 60-year-old man with divergent hormonal levels and who was surgically treated for gynaecomastia: development of abnormally large mammary glands in males. The supplement showed a strong effect in a yeast oestrogen bioassay, expressing a yeast-enhanced green fluorescent protein (yEGFP) upon exposure to oestrogens. Using both nuclear magnetic resonance (NMR) and a gradient liquid chromatographic time-of-flight mass spectrometric (LC/TOF-MS) method, the response was shown to be caused by very high levels of diethylstilbestrol, known for causing gynaecomastia. The gynaecomastia was most probably caused by this orally taken 'natural' herbal supplement, as the patient's hormonal levels also returned to normal again when stopping the use of it. This case demonstrates that physicians need to be aware of the use of supplements with illegal components that may be responsible for unwanted side-effects.

1. Residues of commonly used growth-promoting agents found in animal meat can be hormonally active and they have been implicated as possible endocrine disruptors in man. Although these compounds could be potentially detrimental to the developing foetus, it is not clear whether and to what extent they pass through placental barrier. 2. This issue was addressed using the rabbit as an animal model. Pregnant rabbits were treated with trenbolone acetate, zeranol or melengestrol acetate beginning at gestation day 14. Levels of active substances in plasma were screened by means of specific ELISA systems. The residues of parent compounds and their metabolites were quantified in maternal and foetal tissues on gestation day 27 using validated, sensitive HPLC/ELISA methods. 3. All three compounds crossed the placental barrier and were detectable in foetal tissues. The extent of tissue concentration varied depending on the compound and tissue analysed. Gender differences were observed in some instances.

Women are exposed to xenobiotic estrogens at least to the same extent as men. These estrogenic chemicals are either from plant material in the diet (phytoestrogens) or from industrial sources. Mainly industrially derived environmental estrogens may accumulate within the food chain and persist in human adipose tissue. In contrast, phytoestrogens do not bioaccumulate and are rapidly excreted in urine. The phytoestrogens probably represent the source of most extensive exposure for humans. Epidemiological evidence suggests that diets rich in phytoestrogens are associated with reduced incidences of cardiovascular disease, breast cancer, prostate cancer and osteoporosis. The numerous bioactivities (other than just estrogenicity) of phytoestrogens and related dietary compounds make it difficult to single out the mechanisms mediating such protective effects. The possibility that the newly discovered estrogen receptor beta may be an important modulator of phytoestrogen action is opening up new lines of research. While the evidence suggests that phytoestrogens may be of positive relevance to postmenopausal women, indications that exposure of women to industrially derived xenobiotic estrogens provides risks to health remain unproven. Further work is necessary to clarify the relative importance of 'xenobiotic' estrogens to human health, but it must be emphasized that the estrogenic potency of all the xenobiotic estrogens is very low compared with that of endogenous estrogens.