International audience | Polycyclic aromatic hydrocarbons (PAHs) have been shown to influence endogenous hormones levels in animal models, but little is known about the effects of their mixtures. For hormone measurements, hair analysis is a promising approach to provide information on long-term status of hormones. Herein we used hair analysis to assess the combined effects of 13 PAHs on steroid and thyroid hormones levels in a rat model. The PAH mixture was administered orally three times per week to female rats at doses of 0, 10, 20, 40, 80, 200, 400 and 800 μg/kg of body weight for each compound over a 90-day exposure period. Fourteen out of 36 analyzed hormones were detected in rat hair, including pregnenolone (P5), 17α-hydroxyprogesterone (17-OHP4), corticosterone (CORT), dehydroepiandrosterone (DHEA), androstenedione (AD), 3,3'-diiodo-L-thyronine (T2), 3,3',5-triiodo-L-thyronine (T3), and 3,5,3',5'-triiodo-L-thyronine (T4). The PAH mixture significantly elevated P5 and DHEA levels at the doses of 200 and 400 μg/kg but reduced T2 and T3 levels at the highest dose as compared to the control. While P5, DHEA, 17-OHP4 and AD concentrations exhibited inverted U-shaped dose responses, T2, T3 and T4 concentrations exhibited inverse linear dose responses, which are further confirmed by their relationships with hair hydroxylated PAHs (OH-PAHs) concentrations. Likewise, there were significant nonmonotonic relationships of hormone molar ratios (e.g., AD/17-OHP4 and DHEA/CORT ratios) with exposure intensity and OH-PAHs. Overall, our results demonstrate the capability of PAH mixtures to interfere with steroid and thyroid hormones in female rats.

Insufficient evidence exists regarding the visible physiological toxic endpoints of MPs exposures on zebrafish larvae due to their small sizes. Herein, the impacts of micro-polystyrene particles (μ-PS) and 100 nm polystyrene particles (n-PS) on the toxicity of cadmium (Cd) through altering neutrophil expressions were identified and quantified in the transgenic zebrafish (Danio rerio) larvae Tg(lyz:DsRed2), and the effects were size-dependent. When exposed together with μ-PS, the amount of neutrophils in Cd treated zebrafish larvae decreased by 25.56% through reducing Cd content in the larvae. By contrast, although n-PS exposure caused lower Cd content in the larvae, the expression of neutrophils under their combined exposure remained high. The mechanism of immune toxicity was analyzed based on the results of metabonomics. n-PS induced high oxidative stress in the larvae, which promoted taurine metabolism and unsaturated fatty biosynthesis in n-PS + Cd treatment. This observation was accordance with the significant inhibition of the activities of superoxide dismutase and catalase enzymes detected in their combined treatment. Moreover, n-PS promoted the metabolic pathways of catabolic processes, amino acid metabolism, purine metabolism, and steroid hormone biosynthesis in Cd treated zebrafish larvae. Nanoplasctis widely coexist with other pollutants in the environment at relatively low concentrations. We conclude that more bio-markers of immune impact should be explored to identify their toxicological mechanisms and mitigate the effects on the environment.

Perfluorooctane sulfonate (PFOS), an artificial perfluorinated compound, has been associated with male reproductive disorders. Histone modifications are important epigenetic mediators; however, the impact of PFOS exposure on testicular steroidogenesis through histone modification regulations remains to be elucidated. In this study, we examined the roles of histone modifications in regulating steroid hormone production in male rats chronically exposed to low-level PFOS. The results indicate that PFOS exposure significantly up-regulated the expressions of StAR, CYP11A1 and 3β-HSD, while CYP17A1 and 17β-HSD were down-regulated, thus contributing to the elevated progesterone and testosterone levels. Furthermore, PFOS significantly increased the histones H3K9me2, H3K9ac and H3K18ac while reduced H3K9me3 in rat testis. It is known that histone modifications are closely involved in gene transcription. Therefore, to investigate the association between histone modifications and steroidogenic gene regulation, the levels of these histone marks were further measured in steroidogenic gene promoter regions by ChIP. It was found that H3K18ac was augmented in Cyp11a1 promoter, and H3K9ac was increased in Hsd3b after PFOS exposure, which is proposed to result in the activation of CYP11A1 and 3β-HSD, respectively. To sum up, chronic low-level PFOS exposure activated key steroidogenic gene expression through enhancing histone acetylation (H3K9ac and H3K18ac), ultimately stimulating steroid hormone biosynthesis in rat testis.

Natural and synthetic steroid hormones and many persistent organic pollutants are of concern for their endocrine-disrupting activities observed in receiving surface waters. Apart from the demonstrated presence of estrogen- and estrogen-mimicking compounds in surface waters, antagonistic (anti-estrogenic) responses originating from wastewater effluent have been reported but are less known. Estrogenicity and anti-estrogenicity were assessed using recombinant yeast estrogen receptor binding assays (YES/YAES) at ten South African wastewater treatment works (WWTWs) and receiving rivers in two separate sampling campaigns during the summer- and winter periods in the area. Four WWTWs were then further investigated to show daily variation in estrogenic endocrine-disrupting activities during the treatment process. Although estrogenicity was notably reduced at most of the WWTWs, some treated effluent and river water samples were shown to be above effect-based trigger values posing an endocrine-disrupting risk for aquatic life and potential health risks for humans. Furthermore, estrogenicity recorded in samples collected upstream from some WWTW discharge points also exceeded some calculated risk trigger values, which highlights the impact of alternative pollution sources contributing towards endocrine disrupting contaminants (EDCs) in the environment. The YAES further showed variable anti-estrogenic activities in treated wastewater. The current study highlights a variety of factors that may affect bioassay outcomes and conclusions drawn from the results for risk decision-making. For example, mismatches were found between estrogenic and anti-estrogenic activity, which suggests a potential masking effect in WWTW effluents and highlights the complexity of environmental samples containing chemical mixtures having variable endocrine-disrupting modes of action. Although the recombinant yeast assay is not without its limitations to show endocrine-disrupting modulation in test water systems, it serves as a cost-effective tier-1 scoping assay for further risk characterisation and intervention.

Difenoconazole, a typical triazole fungicide, inhibits lanosterol-14R-demethylase (CYP51) to prevent fungal sterol synthesis and its residues are frequently detected in the environment due to its wide application. Previous studies have demonstrated that difenoconazole altered the triglyceride levels, and gene expression relevant to cholesterol biosynthesis in zebrafish. However, endocrine-disruption in the hypothalamus-pituitary-gonadal-liver (HPGL) axis, the effects of transferring to offspring, and the underlying mechanisms of difenoconazole in aquatic organisms are still unknown. In this study, we defined the effects of difenoconazole at environmental concentrations on endocrine disturbance using zebrafish as an experimental model. The results indicated that difenoconazole induced a significant change in the somatic index, and pathological variations in tissues, and steroid hormone levels. RT-PCR experiments further confirmed that difenoconazole significantly induced expression alteration of lhr, hsd3β, hsd11β, cyp19a in the ovary and star, cyp19a, cyp3c1 in the testis, and erα genes in livers. In addition, difenoconazole exposure in parental zebrafish affected the hatchability and length of its offspring. Moreover, the burdens of difenoconazole and difenoconazole alcohol in females were higher than in males. These findings highlighted that difenoconazole exposure at environmentally relevant concentrations elicited estrogenic endocrine-disruption effects via altering homeostasis of sex steroid hormones in the HPGL axis and the adverse effects can be transferred to the offspring.

This work forwards new insights into the risk-assessment of multi-walled carbon-nanotubes (MWCNTs) while analysing the role of quantum-mechanical interactions between the electrons in the adsorption of probe compounds and biomolecules by MWCNTs. For this, the quantitative models are developed using quantum-chemical descriptors and their electron-correlation contribution. The major quantum-chemical factors contributing to the adsorption are found to be mean polarizability, electron-correlation energy, and electron-correlation contribution to the absolute electronegativity and LUMO energy. The proposed models, based on only three quantum-chemical factors, are found to be even more robust and predictive than the previously known five or four factors based linear free-energy and solvation-energy relationships. The proposed models are employed to predict the adsorption of biomolecules including steroid hormones and DNA bases. The steroid hormones are predicted to be strongly adsorbed by the MWCNTs, with the order: hydrocortisone > aldosterone > progesterone > ethinyl-oestradiol > testosterone > oestradiol, whereas the DNA bases are found to be relatively less adsorbed but follow the order as: guanine > adenine > thymine > cytosine > uracil. Besides these, the developed electron-correlation based models predict several insecticides, pesticides, herbicides, fungicides, plasticizers and antimicrobial agents in cosmetics, to be strongly adsorbed by the carbon-nanotubes. The present study proposes that the instantaneous inter-electronic interactions may be quite significant in various physico-chemical processes involving MWCNTs, and can be used as a reliable predictor for their risk assessment.

In this study we evaluate and demonstrate the occurrence of nine natural and one synthetic steroid hormone, including estrogens, androgens and progestagens in biogas final digestate byproduct (digestion liquid) commonly used as an agricultural fertilizer. We investigated two biogas sites that utilize different anaerobic digestion technologies (mesophilic and thermophilic) from swine manure and other organic wastes. Individual hormone concentration levels were observed up to 1478 ng g−1 dry weight or 22.5 mg kg−1 N with estrone and progesterone reaching highest concentration levels. Evaluation of the potential environmental burden through the application in agriculture was also assessed on the basis of predicted environmental concentrations. This study indicates that the biogas digestion process does not completely remove steroid hormones from livestock manure and use of final digestate byproduct on croplands contributes to the environmental emission of hormones.

Guadipyr, which combines neonicotinoid and semicarbazone functional groups in one molecule, exhibits good activity on several pests and high acute and chronic toxicity to silkworms (Bombyx mori). In this report, the effects of low-dose guadipyr on the midgut microbiota and immune system of silkworms were studied. Results showed that the structure and richness of the midgut microbiota of silkworms were altered after being treated with 5.25 mg/L (1/10 of LC₅₀) of guadipyr. The abundance of Pseudomonas was evidently increased, whereas Curvibacter was substantially reduced, which might be related to the growth and immunity of silkworms. The expression of key genes in the Toll, IMD, and JAK/STAT pathways, which ultimately led to the downregulation of antimicrobial peptide genes (AMPs), such as CecA, Defensin1, Leb, and glv2, was reduced upon guadipyr exposure. Simultaneously, the suppression of steroid hormone 20-hydroxyecdysone receptor and response genes, such as BR-C Z4, was detected in the exposed groups. The decreased expression of these immune regulatory pathway-related and 20-hydroxyecdysone signal pathway-related genes indicated that the immune system of silkworms was affected by low-dose guadipyr. Our results revealed the negative effects of guadipyr on silkworms and highlighted the unneglectable toxicity of low-dose guadipyr to this economic insect. Given the risk, it is necessary to control the application of guadipyr in or around the mulberry fields.

Fluoride mediated disruption of sex steroid hormones has been demonstrated in animals. However, evidence from humans was limited and contradictory, especially for children and adolescents. Based on data of the National Health and Nutrition Survey (NHANES) 2013–2016, a total of 3392 subjects aged 6–19 years were analyzed in this cross-sectional study. Both plasma and water fluoride levels were quantified electrometrically using the ion-specific electrode. Sex steroid hormones of total testosterone, estradiol and sex hormone-binding globulin (SHBG) were tested in serum. Percent changes and 95% confidence intervals (CIs) in sex steroid hormones associated with tertiles of fluoride levels (setting the first as reference) were estimated using adjusted linear regression models by stratification of gender and age. Compared with subjects at the first tertile of plasma fluoride, percent changes (95% CIs) in testosterone were −8.08% (−17.36%, 2.25%) and −21.65% (−30.44%, −11.75%) for the second and third tertiles, respectively (P ₜᵣₑₙd <0.001). Male adolescents at the third tertile of plasma fluoride had decreased levels of testosterone (percent change = −21.09%, 95% CIs = −36.61% to −1.77%). Similar inverse associations were also found when investigating the relationships between plasma fluoride and estradiol. Besides, the data indicated decreased levels of SHBG associated with water and plasma fluoride among the male adolescents (percent change of the third tertile = −9.39%, 95% CIs = −17.25% to −0.78%) and female children (percent change of the second tertile = −10.78%, 95% CIs = −17.55% to −3.45%), respectively. The data indicated gender- and age-specific inverse associations of fluoride in plasma and water with sex steroid hormones of total testosterone, estradiol and SHBG in U.S. children and adolescents. Prospective cohort studies are warranted to confirm the causality.

Glufosinate-ammonium (GLA) is a spectrum herbicide that is widely used in agriculture. The toxic effects of GLA on plants and mammals have been extensively studied; however, little is known about its effects on reptiles. In this study, male lizards (Eremias argus) were exposed to GLA contaminated soil for 60 days. Physical conditions, organ coefficients, antioxidant enzyme activity, tissue distribution, histopathological damage, steroid hormones levels, and related gene expression of sex steroids were evaluated. In contrast to unexposed control lizards, the body mass index of the GLA group was decreased, which elucidated that GLA adversely affected the physical condition of E. argus. Changes in antioxidant enzyme activities in response to elevated malondialdehyde levels in lizard testis indicated that testes were strongly affected by oxidative damage, and the increased testis index was associated with severe testis lesions. Moreover, alterations of plasma sex hormone levels and related gene expression levels of sex steroids were also observed, and the mechanism underlying the induction of reproductive toxicity was clarified. The activity of glutamine synthetase was severely inhibited in the liver of the GLA exposure group. Based on the results of liver index and histopathology examinations, the hepatotoxicity effect of GLA was confirmed.