Effects of Phenanthrene Stress on Gonads and Vitellogenin of Loach (Misgurnus anguillicaudatus).

Phenanthrene (PHE) as a tricyclic polycyclic aromatic hydrocarbon is one of the common pollutants in water and sediments, which can cause reproductive toxicity to aquatic organisms. In this study, enzyme-linked immunosorbent assay (ELISA) was used to detect the vitellogenin (VTG) of loach, and then to explore the estrogenic toxicity effect of PHE on loach. The results were as follows: (1) with the increase of PHE concentrations and the extension of exposure time, the gonadosomatic index (GSI) of males decreased significantly, while it increased in female loaches. In addition, males had more obvious changes than females and were more sensitive to PHE. (2) The increase of VTG contents in serum of males were stronger than that in females. Those results reveal that PHE has estrogenic effect, which can affect the generation of VTG, thus causing damage to the gonad development of loach.

Applicability of the OECD 455 in-vitro assay for determination of hERa agonistic activity of isoflavonoids.

The Organisation for Economic Co-operation and Development (OECD)-validated transactivation assay using the human estrogen receptor alpha (hERα) Hela9903 cell line is used for activity evaluation of hERα agonists and antagonists. Due to many advantages, this assay is broadly used as an initial screening process. However, response significantly higher from that of 17-ß estradiol (E2) was observed with phytoestrogens for concentrations commonly above 1 µM in previous studies. The main aim of this study was thus to ascertain the applicability of OECD protocol 455 for evaluation of estrogenic activity of natural flavonoids, including known phytoestrogens. The estrogenic activities of aglycones as well as of O-methylated and glycosylated flavonoids were evaluated. Supra-maximal luciferase activity was seen for most of the flavonoids tested at concentrations even below 1 µM. hERα-mediated luciferase expression was confirmed with the competition assay specified in OECD protocol 455. However, at concentrations above 1 µM, non-specific interactions were also observed. Instead of EC50 values, which could not be determined for most of the isoflavonoids tested, the concentrations corresponding to 10% (PC10) and 50% (PC50) of the maximum activity of the positive control, E2, were used for quantitative determination of estrogenic activities. Appropriate evaluation of the data obtained with the current OECD protocol 455 validated assay represents a valuable tool for initial screening of natural flavonoids for estrogenic activity.

Royal Jelly-A Traditional and Natural Remedy for Postmenopausal Symptoms and Aging-Related Pathologies.

Women's life stages are based on their reproductive cycle. This cycle begins with menstruation and ends with menopause. Aging is a natural phenomenon that affects all humans, and it is associated with a decrease in the overall function of the organism. In women, aging is related with and starts with menopause. Also, during menopause and postmenopausal period, the risk of various age-related diseases and complaints is higher. For this reason, researchers were pushed to find effective remedies that could promote healthy aging and extended lifespan. Apitherapy is a type of alternative medicine that uses natural products from honeybees, such as honey, propolis, royal jelly, etc. Royal jelly is a natural yellowish-white substance, secreted by both hypopharyngeal and mandibular glands of nurse bees, usually used to feed the queen bees and young worker larvae. Over the centuries, this natural product was considered a gold mine for traditional and natural medicine, due to its miraculous effects. Royal jelly has been used for a long time in commercial medical products. It has been demonstrated to possess a wide range of functional properties, such as: antibacterial, anti-inflammatory, vasodilatative, hypotensive, anticancer, estrogen-like, antihypercholesterolemic, and antioxidant activities. This product is usually used to supplement various diseases such as cardiovascular disease, Alzheimer's disease, sexual dysfunctions, diabetes or cancer. The main objective of this study is to highlight the effectiveness of royal jelly supplementation in relieving menopause symptoms and aging-related diseases. We also aimed to review the most recent research advances regarding the composition of royal jelly for a better understanding of the effects on human health promotion.

Estrogenic effects of fluorinated diiodine alkanes in MCF-7 cells, H295R cells and zebrafish embryo assays.

Fluorinated diiodine alkanes (FDIAs), important industrial intermediates in the synthesis of various perfluorinated compounds, which are distributed widely in wildlife and humans. Recent studies showed that FDIAs had in vitro estrogenic effects. However, to date, little information is available regarding the in vivo estrogenic effects of FDIAs and the mechanisms are unclear. In this study, a combination of in vitro and in vivo assays was used to investigate the estrogenic effects of FDIAs. We tested the in vitro estrogenic effects and estrogen receptor-related gene expression via MCF-7 cell assay. The hormone level of estradiol and the expression of estrogenic synthesis genes were measured in the H295R cell assay. Finally, the in vivo effects of FDIAs on development and estrogen-related gene expression were assessed in the zebrafish embryos assay. The results demonstrated that FDIAs could exhibit estrogenic activity through inducing cell proliferation (1.6-6.7-fold of the control) and estrogen receptor alpha gene expression (1.07-1.39-fold of the control), altering estradiol production (1.14-1.22-fold of the control) and the major estrogenic synthesis gene expression of CYP19 (1.22-1.31-fold of the control), disrupting the estrogen-related genes (esr1 and cyp19b) levels in zebrafish (1.52-2.99-fold and 2.95-5.00-fold of the control for esr1 and cyp19b, respectively). The current findings indicated the potential estrogenic effects of FDIAs and provided novel information for human risk assessment.

Is frying oil a dietary source of an endocrine disruptor? Anti-estrogenic effects of polar compounds from frying oil in rats.

The objective was to investigate endocrine-disrupting effects of polar compounds from oxidized frying oil. Estrogenicity of polar compounds was tested with a rat uterotrophic bioassay. Dietary oxidized frying oil (containing 51% polar compounds) or polar compounds isolated from it were incorporated into feed (in lieu of fresh soybean oil) and fed to ovariectomized rats, with or without treatment with exogenous ethynyl estradiol. Exogenous estrogen restored uterine weight, and caused histological abnormalities (stratified epithelia and conglomerate glands) as well as proliferation of uterine epithelial cells. However, tamoxifen or polar compounds reduced these effects. Furthermore, tamoxifen or polar compounds down-regulated uterine mRNA expression of estrogen receptor (ER)-target genes, implicating reduced ER activity in this hypo-uterotrophic effect. Inhibition of ER signaling and mitosis by polar compounds were attributed to reduced MAPK and AKT activation, as well as a reduced ligand binding domain-transactivity of ERα/ß. We concluded polar compounds from frying oil are potential endocrine-disrupting chemicals, with implications for food and environmental safety.

Radix Paeoniae Alba increases serum estrogen level and up-regulates estrogen receptor expression in uterus and vagina of immature/ovariectomized mice.

Radix Paeoniae Alba (RPA) is widely used in clinical treatment for gynecological diseases, particularly abnormal menstruation, menstrual pain, and breast tenderness; however, no scientific evidence base links RPA to estrogen replacement therapy. In this study, we characterize estrogenic activity of RPA using immature and ovariectomized (OVX) mice together with in vitro studies focus on estrogen receptor (ER) pathway for molecular mechanism. RPA treatments demonstrated significant estrogenic activity, as indicated by promoting the development of uterus and vagina in immature mice, reversing the atrophy of uterus and vagina in OVX mice, up-regulating the expressions of ERα and ERß at protein and mRNA level in reproductive tissues. Meanwhile, RPA significantly increased serum estradiol and clearly decreased serum luteinizing hormone and follicle-stimulating hormone of immature/OVX mice. Moreover, RPA could induce ER positive MCF-7 cell from S-phase to G2 stage and induce proliferation and no influence on ER negative MDA-MB-231 cell. RPA could bind with ERα and ERß and significantly stimulate ERα/ß-estrogen response element (ERE) luciferase reporter gene expression. All activities were inhibited by the ER antagonist ICI 182,780. This study illustrates RPA exerts estrogenic effects by stimulating biosynthesis of estrogen in circulation, up-regulating ERs in target tissues, and mimicking the estrogen through ER-ERE-dependent pathway.

Estrogenic activity of constituents from the rhizomes of Rheum undulatum Linné.

Stilbenes have been reported to be phytoestrogen compounds owing to its structural similarity to the estrogenic agent diethylstilbestrol. To find new stilbene-derivative phytoestrogens, isolation of stilbene-rich R. undulatum was performed and led to identify six new compounds (1-5 and 28), one newly determined absolute configurations compound (27) together with 21 previously reported compounds (6-26). The structures of compounds were determined on the basis of extensive spectroscopic methods including 1D and 2D NMR and CD spectra data. All the isolated compounds were tested for their estrogenic activities in HepG2 cells transiently transfected with ERα, ERß and ERE-reporter plasmid. Among them, stilbene-derivatives, piceatannol 3'-O-ß-d-xylopyranoside (12), cis-rhaponticin (16) and rhapontigenin 3'-O-ß-d-glucopyranoside (17), showed the more potent binding affinity for estrogen receptors than 17ß-estrodiol.

Perfluorinated chemicals, PFOS and PFOA, enhance the estrogenic effects of 17ß-estradiol in T47D human breast cancer cells.

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are the two most popular surfactants among perfluorinated compounds (PFCs), with a wide range of uses. Growing evidence suggests that PFCs have the potential to interfere with estrogen homeostasis, posing a risk of endocrine-disrupting effects. This in vitro study aimed to investigate the estrogenic effect of these compounds on T47D hormone-dependent breast cancer cells. PFOS and PFOA (10(-12) to 10(-4) M) were not able to induce estrogen response element (ERE) activation in the ERE luciferase reporter assay. The ERE activation was induced when the cells were co-incubated with PFOS (10(-10) to 10(-7) M) or PFOA (10(-9) to 10(-7) M) and 1 nM of 17ß-estradiol (E2). PFOS and PFOA did not modulate the expression of estrogen-responsive genes, including progesterone (PR) and trefoil factor (pS2), but these compounds enhanced the effect of E2-induced pS2 gene expression. Neither PFOS nor PFOA affected T47D cell viability at any of the tested concentrations. In contrast, co-exposure with PFOS or PFOA and E2 resulted in an increase of E2-induced cell viability, but no effect was found with 10 ng ml(-1) EGF co-exposure. Both compounds also intensified E2-dependent growth in the proliferation assay. ERK1/2 phosphorylation was increased by co-exposure with PFOS or PFOA and E2, but not with EGF. Collectively, this study shows that PFOS and PFOA did not possess estrogenic activity, but they enhanced the effects of E2 on estrogen-responsive gene expression, ERK1/2 activation and the growth of the hormone-deprived T47D cells. Copyright © 2015 John Wiley & Sons, Ltd.

Electrochemistry detection of estrogenic effect: Regulation of de novo purine synthesis and catabolism by gibberellin and fulvestrant.

The estrogenic effect of plant growth regulators has been received little attention, which leads to the lack of relevant toxicity data. In this study, the estrogenic effect induced by gibberellin with ERα-dependent manner was found by E-screen and western blot methods, and the electrochemical signals of MCF-7 cells regulated by gibberellin and fulvestrant were investigated. The results showed that the electrochemical signals of MCF-7 cells were increased by gibberellin, while reduced by fulvestrant significantly, and displayed an extremely sensitive response to the effects of estrogenic effect induced by ERα agonist and antagonist. Western blot results showed that the expressions of phosphoribosyl pyrophosphate amidotransferase and hypoxanthine nucleotide dehydrogenase in de novo purine synthesis and adenine deaminase in catabolism were more effective regulated by gibberellin and fulvestrant, resulting in significant changes of the levels of guanine, hypoxanthine and xanthine in cells, and then electrochemical signals. The results provide a theoretical basis for the establishment of new electrochemical detection method of the estrogenic effect of plant regulators.

Degradation of conjugated estrogen in visible light-driven intimately coupled photocatalysis and biodegradation system.

Visible light-driven intimately coupled photocatalysis and biodegradation (VDICPB) is an efficient technology for removing recalcitrant contaminants, but the degradation pathway on 17ß-estradiol 3-Sulfate (E2-3S) is still not clear. In this study, VDICPB based on N-doped TiO2 as a photocatalyst was established to investigate the removal and transformation of E2-3S in synthetic wastewater. VDICPB showed a satisfactory removal efficiency of 97.8 ± 0.4 %, which was much higher than that of independent photocatalysis (84.0 ± 2.2 %) or biodegradation system (71.4 ± 1.8 %). Steroid C/D-rings of E2-3S was broken in VDICPB since the transformation process reached terminal central pathway. Primary metabolites did not accumulate in VDICPB, resulting in a low expression of functional genes. E2-3S was mainly removed by cooperative interaction of photocatalysis and co-metabolism of biofilm. Photocatalysis led to deconjugation and microbes acted to mineralization. This study provides technical reference and theoretical support for the removal of new pollutants.

Can a shift in dominant species of Microcystis alter growth and reproduction of waterfleas?

The bloom-forming species Microcystis wesenbergii and M. aeruginosa occur in many lakes globally, and may exhibit alternating blooms both spatially and temporally. As environmental changes increase, cyanobacteria bloom in more and more lakes and are often dominated by M. wesenbergii. The adverse impact of M. aeruginosa on co-existing organisms including zooplanktonic species has been well-studied, whereas studies of M. wesenbergii are limited. To compare effects of these two species on zooplankton, we explored effects of exudates from different strains of microcystin-producing M. aeruginosa (Ma905 and Ma526) and non-microcystin-producing M. wesenbergii (Mw908 and Mw929), on reproduction by the model zooplankter Daphnia magna in both chronic and acute exposure experiments. Specifically, we tested physiological, biochemical, molecular and transcriptomic characteristics of D. magna exposed to Microcystis exudates. We observed that body length and egg and offspring number of the daphnid increased in all treatments. Among the four strains tested, Ma526 enhanced the size of the first brood, as well as total egg and offspring number. Microcystis exudates stimulated expression of specific genes that induced ecdysone, juvenile hormone, triacylglycerol and vitellogenin biosynthesis, which, in turn, enhanced egg and offspring production of D. magna. Even though all strains of Microcystis affected growth and reproduction, large numbers of downregulated genes involving many essential pathways indicated that the Ma905 strain might contemporaneously induce damage in D. magna. Our study highlights the necessity of including M. wesenbergii into the ecological risk evaluation of cyanobacteria blooms, and emphasizes that consequences to zooplankton may not be clear-cut when assessments are based upon production of microcystins alone.

Endocrine disrupting effect and reproductive toxicity of the separate exposure and co-exposure of nano-polystyrene and diethylstilbestrol to zebrafish.

The co-occurrence of nanoplastics and other pollutants in the environment has gotten a lot of attention, but information on the biological toxicity of their co-exposure was limited. This study aims to reveal the endocrine disrupting effect and reproductive toxicity of nano-polystyrene (NPS) and diethylstilbestrol (DES) to zebrafish under separate and combined exposure. Results indicated that NPS and DES exposure in isolation reduced the hepatosomatic index and gonadosomatic index, and altered the cell maturity in gonads in both cases. Even worse, the co-exposure of NPS and DES exacerbated the damage to the liver and gonads of fish. The two pollutants individually inhibited the secretion of sex hormones and vitellogenin. The inhibition effect of DES was especially dose-dependent, while NPS had weaker effect than DES. Their combined action on the secretion of sex hormones and vitellogenin exhibited additive effect. However, NPS did not affect the content of thyroid hormones in fish, and also had no significant effect on the reduction of thyroid hormone caused by DES exposure. Furthermore, their co-exposure decreased the cumulative eggs from 1031 to 306, and the spawning number from 12 to 8. The fertilization rate and hatchability rete of eggs were reduced by 30.9% and 40.4%, respectively. The abnormality rate of embryos was 65.0%, significantly higher than in separate DES and NPS groups (55.7% and 30.8% respectively). The abnormal development of offspring was mainly pericardial cyst, spinal curvature, and growth retardation.

Twelve natural estrogens and ten bisphenol analogues in eight drinking water treatment plants: Analytical method, their occurrence and risk evaluation.

Bisphenol analogues (BPs) and natural estrogens (NEs) as two important groups of endocrine-disrupting compounds (EDCs) in drinking water treatment plants (DWTPs) have been hardly investigated except bisphenol A (BPA) and three major NEs including estrone (E1), 17ß-estradiol (E2) and estriol (E3). In this study, a GC-MS analytical method was firstly established and validated for trace simultaneous determination of ten BPs and twelve NEs in drinking water, which included BPA, bisphenol B (BPB), bisphenol C (BPC), bisphenol E (BPE), bsiphenol F (BPF), bsiphenol P (BPP), bisphenol S (BPS), bisphenol Z (BPZ), bisphenol AF (BPAF), bisphenol AP (BPAP), E1, E2, E3, 17α-estradiol (17α-E2), 2-hydroestrone (2OHE1), 16hydroxyestrone (16α-OHE1), 4-hydroestrone (4OHE1), 2-hydroxyesstradiol (2OHE2), 4-hydroxyestradiol (4OHE2), 17-epiestriol (17epiE3), 16-epiestriol (16epiE3) and 16keto-estraiol (16ketoE2). This investigation showed that eighteen out of twenty-two targeted compounds were detected in drinking source waters of eight DWTPs with concentrations ranging from not detected to 142.8 ng/L. Although the conventional treatment process of DWTP could efficiently remove both BPs and NEs with respective removal efficiencies of 74.1%-90.9% and 74.5%-100%, BPA, BPS, BPE, BPZ, E1, 2OHE1, and 2OHE2 were found in the finished drinking waters. Chlorination could remove part of BPs and NEs, but the efficiency varied greatly with DWTP and the reason was unknown. In the finished drinking waters of eight DWTPs, the highest chemically calculated estrogen equivalence (EEQ) derived from BPs and NEs was up to 6.11 ngE2/L, which was over 22 times that could do harm to zebrafish, indicating a potential risk to human health. Given the fact that many chlorination products of BPs and NEs likely have higher estrogenic activities, the estrogenic effect of BPs and NEs in finished drinking water should be accurately examined urgently with the inclusion of BPs, NEs as well as their main chlorinated by-products. This study shed new light on the occurrence, removal, and potential estrogenic effects of BPs and NEs in DWTPs.

Estrogenic Effect Mechanism and Influencing Factors for Transformation Product Dimer Formed in Preservative Parabens Photolysis.

The environmental transformation and health effects of endocrine disruptors (EDCs) need urgent attention, particularly the formation of transformation products with higher toxicity than parent EDCs. In this paper, an important transformation product dimer (short for ethyl 4-hydroxy-3-(2-((4-hydroxybenzoyl) oxy) ethyl) benzoate) with estrogenic activity was investigated and detected in the photolysis of preservative ethyl-paraben (EPB) dissolved in actual water. The environmental factors, such as the higher initial concentration of EPB, the stronger optical power and the lower pH could stimulate the formation of the dimer. Simultaneously, the interaction of multiple environmental factors was significant, especially the initial concentration and pH using the response surface methodology. Furthermore, the relationship between the environmental factors and the formation of the product dimer was further explained and the empirical model equation was built for predicting the amount of dimer in actual water. Quantum chemical and toxicological calculations showed the estrogenic effect mechanism of the product dimer and it was revealed further that the hydrogen bonds of the dimer and ERα proteins (ARG-394, Glu-353, His-524, GYY-521) were formed, with a lowest binding energy of -8.38 Kcal/mol during molecular docking. In addition, the health effect risk of the product dimer was higher than the parent compound in the blood, cardiovascular system, gastrointestinal system, kidney and liver. In short, the present study was of great significance for the transformation product in pollution control and health effects in the photolysis of EDCs.

Activation of estrogen-related receptor: An alternative mechanism of hexafluoropropylene oxide homologs estrogenic effects.

Perfluorooctanoic acid (PFOA) alternatives such as hexafluoropropylene oxide homologs (HFPOs) cause concern due to increased occurrence in the environment as well as potential bioaccumulation and toxicity. HFPOs have been demonstrated to activate the estrogen receptor (ER) pathway. The ER pathway is homologous and connected to the estrogen-related receptor (ERR) pathway, but HFPOs effects on the ERR pathway have not been studied. Hence, we assessed the potential estrogenic effects of HFPOs via ERRγ pathway. In vitro assays revealed that HFPO dimeric, trimeric, and tetrameric acids (HFPO-DA, -TA, and -TeA, respectively), acted as ERRγ agonists, activating the transcription of both human and zebrafish ERRγ at low concentrations, but inhibiting zebrafish ERRγ at high concentrations. We also found that HFPO-TA promoted the human endometrial cancer cells (Ishikawa cells) proliferation via ERRγ/EGF, Cyclin D1 pathway. The HFPO-TA-induced proliferation of Ishikawa cells was inhibited by co-exposure with a specific antagonist of ERRγ, GSK5182. In vivo exposure of female zebrafish to HFPO-TA disturbed sex hormone levels, interfered with the gene expression involved in estrogen synthesis and follicle regulation, and caused histopathological lesions in the ovaries, which were similar to those induced by a known ERRγ agonist GSK4716. Taken together, this study revealed a new mechanism concerning the estrogenic effect of HFPOs via activation of the ERRγ pathway.

Comparative in vitro and in silico study on the estrogenic effects of 2,2-bis(4-chlorophenyl)ethanol, 4,4'-dichlorobenzophenone and DDT analogs.

DDT and its transformation products (DDTs) are frequently detected in environmental and biological media. Research suggests that DDT and its primary metabolites (DDD and DDE) could induce estrogenic effects by disturbing estrogen receptor (ER) pathways. However, the estrogenic effects of DDT high-order transformation products, and the exact mechanisms underlying the differences of responses in DDT and its metabolites (or transformation products) still remain unknown. Here, besides DDT, DDD and DDE, we selected two DDT high-order transformation products, 2,2-bis(4-chlorophenyl) ethanol (p,p'-DDOH) and 4,4'-dichlorobenzophenone (p,p'-DCBP). We aim to explore and reveal the relation between DDTs activity and their estrogenic effects by receptor binding, transcriptional activity, and ER-mediated pathways. Fluorescence assays showed that the tested 8 DDTs bound to the two isoforms (ERα and ERß) of ER directly. Among them, p,p'-DDOH exhibited the highest binding affinity, with IC50 values of 0.43 µM and 0.97 µM to ERα and ERß, respectively. Eight DDTs showed different agonistic activity toward ER pathways, with p,p'-DDOH exhibiting the strongest potency. In silico studies revealed that the eight DDTs bound to either ERα or ERß in a similar manner to 17ß-estradiol, in which specific polar and non-polar interactions and water-mediated hydrogen bonds were involved. Furthermore, we found that 8 DDTs (0.0008-5 µM) showed distinct pro-proliferative effects on MCF-7 cells in an ER-dependent manner. Overall, our results revealed not only for the first time the estrogenic effects of two DDT high-order transformation products by acting on ER-mediated pathways, but also the molecular basis for differential activity of 8 DDTs.

Assessing the toxicity of bisphenol A and its six alternatives on zebrafish embryo/larvae.

Bisphenol A (BPA) analogues are gradually replacing BPA in the plastics industry. Whether these alternatives are indeed safer than BPA itself, however, remains unclear. Here, we studied the toxicity of BPA and six of its alternatives-BPB, BPC, BPE, BPF, BPAF, and BPAP-using zebrafish embryos/larvae. According to their half lethal concentration (LC50) values, the acute toxicity of BPA and six alternative bisphenols to zebrafish embryos, from highest to lowest, was BPAP ≈ BPAF > BPC > BPB > BPA > BPE > BPF. Under nonlethal concentrations, the tested bisphenols had different toxic effects on development in terms of reducing the hatching rate, frequency of spontaneous movements, and heart rate in the embryo, as well as inducing yolk sac edema, pericardial edema, and spinal deformation in the larvae. The estrogenic activity of BPE, BPF, and BPAF was higher than that of BPA, as shown by vtg1 expression assays. Moreover, BPA and its alternatives increased SOD activity and cell apoptosis in embryos/larvae under nonlethal concentrations. Our findings indicate that BPA alternatives may not be safer than BPA in zebrafish, and that these BPA alternatives should be applied with caution.

Transgenerational effects of androstadienedione and androstenedione at environmentally relevant concentrations in zebrafish (Danio rerio).

Androgens androstadienedione (ADD) and androstenedione (AED) are predominant steroid hormones in surface water, and can disrupt the endocrine system in fish. However, little is known about the transgenerational effects of ADD and AED in fish. In the present study, F0 generation was exposed to ADD and AED from 21 to 144 days post-fertilization (dpf) at nominal concentrations of 5 (L), 50 (M) and 500 (H) ng L-1, and F1 generation was domesticated in clear water for 144 dpf. The sex ratio, histology and transcription in F0 and F1 generations were examined. In the F0 generation, ADD and AED tended to be estrogenic in zebrafish, resulting in female biased zebrafish populations. In the F1 generation, ADD at the H level caused 63.5% females, while AED at the H level resulted in 78.7% males. In brain, ADD and AED had similar effects on circadian rhythm in the F0 and F1 generations. In the F1 eleutheroembryos, transcriptomic analysis indicated that neuromast hair cell related biological processes (BPs) were overlapped in the ADD and AED groups. Taken together, ADD and AED at environmentally relevant concentrations had transgenerational effects on sex differentiation and transcription in zebrafish.

Direct Effects of Glyphosate on In Vitro T Helper Cell Differentiation and Cytokine Production.

Glyphosate (G) is the active ingredient of the most used herbicides worldwide. Its use is currently very debated, as several studies indicating its hazard and toxicity are emerging. Among them, there is evidence of adverse effects on the immune system. The aim of this work was to investigate if G could directly affect immune cells. Peripheral blood mononuclear cells (PBMC) obtained from healthy donors were used as experimental model. PBMC were expose to G and stimulated with PMA/ionomycin, T helper (Th) cell differentiation and cytokine production were assessed by flow cytometry and enzyme-linked immunosorbent assay, respectively. A reduction of Th1/Th2 ratio, mainly due to a decrease in Th1 cells, was observed following G exposure. Results show an enhancement of IL-4 and IL-17A production, and a reduction of IFN-γ. Based on literature evidence that suggest G being an endocrine disruptor, we investigated the role of nuclear estrogen receptors (ER). ERα/ERß inhibition by ICI 182,780 abolished the effects of G on IFN-γ and IL-4 release, suggesting a role of ER in the observed effects. To further characterize the mechanism of action of G, miRNAs, both in exosome and intracellular, were investigated. A statistically significant increase in miR-500a-5p was observed following G treatment. The blockage of miR-500a-5p, using a specific antagomir, prevented G-induced reduction of IFN-γ production. Finally a relationship between miR-500a-5p up-regulation and ER was observed. Overall, these results suggest that G can directly act on T cells, altering T cell differentiation and cytokines production.

Occurrence, spatial distribution, and main source identification of ten bisphenol analogues in the dry season of the Pearl River, South China.

Bisphenol analogues (BPs) including bisphenol a (BPA) have been broadly utilized as industrial feedstocks and unavoidably discharged into water bodies. However, there is little published data on the occurrence, distribution, and environmental risks of other BPs in surface water. In this study, ten BPs besides BPA were analyzed in surface water from the Pearl River, South China. Among these detected BPs, BPA, bisphenol F (BPF), bisphenol AF (BPAF), and bisphenol S (BPS) were the most frequently detected compounds. The median concentrations of the measured BPs were ranked in the order of BPA (34.9 ng/L) > BPS (24.8 ng/L) > BPAF (10.1 ng/L) > bisphenol F (BPF) (9.0 ng/L) > bisphenol B (BPB) (7.6 ng/L) > bisphenol C (BPC) (1.2 ng/L). Among them, BPA and BPS were predominant BPs, contributing 68% of the total ten BPs in surface water of the Pearl River. These results demonstrated that BPA and BPS were the most extensively utilized and manufactured BPs in this region. The source analysis of BPs suggested that the BPs may be originated from domestic wastewater, wastewater treatment plant (WWTP) effluent, and the leaching of microplastic in surface water of the Pearl River. The calculated BP-derived estrogenic activity exhibited low to medium risks in surface water, but their combined estrogenic effects with other endocrine disrupting compounds should not be ignored.