Maternal intake of paracetamol during pregnancy and biomarkers of male fecundity in young adult sons.

Paracetamol is suggested to have endocrine disrupting properties possibly affecting fetal programming of reproductive health that might lead to impaired semen quality and changes in reproductive hormones. In this longitudinal study, we included 1058 young adult men born 1998-2000 into the Danish National Birth Cohort with follow-up at 18-21 years of age. The exposure, maternal intake of paracetamol, was modelled in three ways: dichotomized, trimester-specific, and as duration of exposure categorized into: short (1-2 weeks), medium (3-9 weeks) or long duration (>9 weeks) vs. no intake. Outcomes included semen characteristics, self-measured testis volume, and reproductive hormone levels. We used negative binominal regression to estimate the percentage difference and 95% confidence interval (CI) for each outcome. In total, 547 (48%) sons were prenatally exposed to paracetamol due to maternal intake at least once. Maternal intake of paracetamol during pregnancy was not associated with any of the biomarkers in the dichotomized or trimester-specific exposure models. For duration of exposure, sons of mothers with long duration of maternal intake of paracetamol showed tendencies towards lower semen concentration (-14% [95% CI: -31%; 8%]), a higher proportion of nonprogressive and immotile spermatozoa (8% [95% CI: -4%; 21%]) and higher DNA Fragmentation Index (16% [95% CI: -1%; 36%]) compared to son of mothers with no intake. Maternal intake of paracetamol during pregnancy was not clearly associated with biomarkers of male fecundity in adult sons. However, it cannot be ruled out that long duration of maternal intake of paracetamol might be associated with impaired semen characteristics.

The research landscape concerning environmental factors in neurodevelopmental disorders: Endocrine disrupters and pesticides-A review.

In recent years, environmental epidemiology and toxicology have seen a growing interest in the environmental factors that contribute to the increased prevalence of neurodevelopmental disorders, with the purpose of establishing appropriate prevention strategies. A literature review was performed, and 192 articles covering the topic of endocrine disruptors and neurodevelopmental disorders were found, focusing on polychlorinated biphenyls, polybrominated diphenyl ethers, bisphenol A, and pesticides. This study contributes to analyzing their effect on the molecular mechanism in maternal and infant thyroid function, essential for infant neurodevelopment, and whose alteration has been associated with various neurodevelopmental disorders. The results provide scientific evidence of the association that exists between the environmental neurotoxins and various neurodevelopmental disorders. In addition, other possible molecular mechanisms by which pesticides and endocrine disruptors may be associated with neurodevelopmental disorders are being discussed.

Enhanced biodegradation of microplastic and phthalic acid ester plasticizer: The role of gut microorganisms in black soldier fly larvae.

Hermetia illucens larvae are recognized for their ability to mitigate or eliminate contaminants by biodegradation. However, the biodegradation characteristics of microplastics and phthalic acid esters plasticizers, as well as the role of larval gut microorganisms, have remained largely unrevealed. Here, the degradation kinetics of plasticizers, and biodegradation characteristics of microplastics were examined. The role of larval gut microorganisms was investigated. For larval development, microplastics slowed larval growth significantly (P < 0.01), but the effect of plasticizer was not significant. The degradation kinetics of plasticizers were enhanced, resulting in an 8.11 to 20.41-fold decrease in degradation half-life and a 3.34 to 3.82-fold increase in final degradation efficiencies, compared to degradation without larval participation. The depolymerization and biodeterioration of microplastics were conspicuously evident, primarily through a weight loss of 17.63 %-25.52 %, variation of chemical composition and structure, bio-oxidation and bioerosion of microplastic surface. The synergistic effect driven by larval gut microorganisms, each with various functions, facilitated the biodegradation. Specifically, Ignatzschineria, Paenalcaligenes, Moheibacter, Morganella, Dysgonomonas, Stenotrophomonas, Bacteroides, Sphingobacterium, etc., appeared to be the key contributors, owing to their xenobiotic biodegradation and metabolism functions. These findings offered a new perspective on the potential for microplastics and plasticizers biodegradation, assisted by larval gut microbiota.

Removal characteristics of 53 micropollutants during ozonation, chlorination, and UV/H2O2 processes used in drinking water treatment plant.

The removal of 53 emerging micropollutants (MPs), including 10 per- and polyfluorinated substances (PFASs), 25 pharmaceuticals and personal care products (PPCPs), 7 pesticides, 5 endocrine disrupters (EDCs), 3 nitrosamines, and 3 taste and odor compounds (T&Os), by chlorination, ozonation, and UV/H2O2 treatment was examined in deionized water and surface waters used as the raw waters in drinking water treatment plants (DWTPs) in South Korea. The UV/H2O2 treatment was effective in the removal of most MPs, whereas chlorination was selectively effective for 19 MPs, including EDCs (>70 %). MPs containing aromatic ring with electron-donating functional group, or primary and secondary amines were effectively removed by chlorination immediately upon reaction initiation. The removal of MPs by ozonation was generally lower than that of the other two processes at a low ozone dose (1 mg L-1), but higher than chlorination at a high ozone dose (3 mg L-1), particularly for 16 MPs, including T&Os. Compared in deionized water, the removals of MPs in the raw water samples were lower in all three processes. The regression models predicting the rate constants (kobs) of 53 MPs showed good agreement between modeled and measured value for UV/H2O2 treatment (R2 = 0.948) and chlorination (R2 = 0.973), despite using only dissolved organic carbon (DOC) and oxidant concentration as variables, whereas the ozonation model showed a variation (R2 = 0.943). Our results can provide the resources for determining which oxidative process is suitable for treating specific MPs present in the raw waters of DWTPs.

Using Hepatic Gene Expression Assays in English Sole (Parophrys vetulus) to Investigate the Effects of Metro Vancouver Wastewater Effluents.

The present study has investigated the effects of Metro Vancouver's wastewater treatment plant (WWTP) effluents on English sole (Parophrys vetulus) hepatic gene expression using novel targeted gene expression assays to complement the 2017 Burrard Inlet Ambient Monitoring Program conducted by Metro Vancouver. Seven locations of varying distance to the WWTPs were included. Twelve genes involved in xenobiotic defense (CYP1A, HSP70), thyroid function (DIO1), lipid and glucose metabolism (FABP1, FASN, GLUT2, PPARδ, PPARγ), protein synthesis (18S rRNA, RPS4X), and reproduction (ERα, VTG) revealed several differences between these impacted sites. A key finding of the present study was that males exhibited VTG transcript levels either equivalent or exceeding female levels of this gene at all sites investigated, indicating widespread exposure of estrogenic contaminants throughout Burrard Inlet. Furthermore, the induction of hepatic CYP1A was observed due to possible downstream sites being subjected to a larger influx of certain planar halogenated and non-halogenated hydrocarbons from multiple industrial contributors. This study also revealed significant differences between the sites examined and in genes involved in transcriptional regulation and synthesis of proteins, lipids and glucose metabolism, and thyroid hormone metabolism. Collectively, this study demonstrates the potential of molecular biomarkers of urban contaminant exposure in wild caught English sole for use in diagnosing a broader range of adverse health effects when combined with conventional whole organism health indicators.

2,3,7,8-tetrachlorodibenzo-p-dioxin induces multigenerational testicular toxicity and biosynthetic disorder of testosterone in BALB/C mice: Transcriptional, histopathological and hormonal determinants.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent environmental contaminant, is an endocrine disrupter with a proven reproductive toxicity in mammals. However, its effects on male fertility across generations are still elusive. The current work evaluates the toxicity of dioxin on male reproductive system in two separate groups of BALB/C mice; a group of pubertal males directly exposed to TCDD (referred to as DEmG), and a group of indirectly exposed males (referred to as IDEmG) comprises of F1, F2 and F3 males born from TCDD-exposed pregnant females. Both groups were exposed to 25 µg TCDD/kg body weight for a week. Our data show that males of TCDD-DEmG exhibited significant alterations in the expression of certain genes involved in the detoxification of TCDD and the biosynthesis of testosterone. This was accompanied with testicular pathological symptoms, including a sloughing in the germinal epithelium and a congestion of blood vessels in interstitial tissue with the presence of multinuclear cells into seminiferous tubule, with a 4-fold decline in the level of serum testosterone and reduced sperm count. Otherwise, the male reproductive toxicity across F1, F2 and F3 generations from TCDD-IDEmG was mainly characterized by: i) a reduce in body and testis weight. ii) a decrease in gene expression of steriodogenesis enzyme, e.g., AhR, CYP1A1, CYP11A1, COX1, COX2, LOX5 and LOX12. iii) a remarked and similar testicular histopathology that found for DEmG, iv) a serious decline in serum testosterone. v) a decreased male-to-female ratio. vi) a low sperm count with increasing abnormalities. Thus, pubertal or maternal exposure to TCDD provokes multigenerational male reproductive toxicity in mice, ultimately affecting the spermatogenesis and suggesting that the hormonal alternation and sperm abnormality are the most marked effects of the indirect exposure of mammalian male to TCDD.

TRIAC disrupts cerebral thyroid hormone action via negative feedback and heterogenous distribution among organs.

As 3,3',5-triiodothyroacetic acid (TRIAC), a metabolite of thyroid hormones (THs), was previously detected in sewage effluent, we aimed to investigate exogenous TRIAC's potential for endocrine disruption. We administered either TRIAC or 3,3',5-triiodo-L-thyronine (LT3) to euthyroid mice and 6-propyl-2-thiouracil-induced hypothyroid mice. In hypothyroid mice, TRIAC administration suppressed the hypothalamus-pituitary-thyroid (HPT) axis and upregulated TH-responsive genes in the pituitary gland, the liver, and the heart. We observed that, unlike LT3, TRIAC administration did not upregulate cerebral TH-responsive genes. Measurement of TRIAC contents suggested that TRIAC was not efficiently trafficked into the cerebrum. By analyzing euthyroid mice, we found that cerebral TRIAC content did not increase despite TRIAC administration at higher concentrations, whereas serum levels and cerebral contents of THs were substantially decreased. Disruption by TRIAC is due to the additive effects of circulating endogenous THs being depleted via a negative feedback loop involving the HPT axis and heterogeneous distribution of TRIAC among different organs.

A novel co-culture model of human prostate epithelial and stromal cells for androgenic and antiandrogenic screening.

The risk assessment of endocrine-disrupting chemicals (EDCs) greatly relies on in vitro screening. A 3-dimensional (3D) in vitro prostate model that can reflect physiologically-relevant prostate epithelial and stromal crosstalk can significantly advance the current androgen assessment. This study built a prostate epithelial and stromal co-culture microtissue model with BHPrE and BHPrS cells in scaffold-free hydrogels. The optimal 3D co-culture condition was defined, and responses of the microtissue to androgen (dihydrotestosterone, DHT) and anti-androgen (flutamide) exposure were characterized using molecular and image profiling techniques. The co-culture prostate microtissue maintained a stable structure for up to seven days and presented molecular and morphological features of the early developmental stage of the human prostate. The cytokeratin 5/6 (CK5/6) and cytokeratin 18 (CK18) immunohistochemical staining indicated epithelial heterogeneity and differentiation in these microtissues. The prostate-related gene expression profiling did not efficiently differentiate androgen and anti-androgen exposure. However, a cluster of distinctive 3D image features was identified and could be applied in the androgenic and anti-androgenic effect prediction. Overall, the current study established a co-culture prostate model that provided an alternative strategy for (anti-)androgenic EDC safety assessment and highlighted the potential and advantage of utilizing image features to predict endpoints in chemical screening.

Differences in Age-Related Changes in the Thymus in Rats Developmentally Exposed to Endocrine Disrupter Dichlorodiphenyltrichloroethane.

We studied features of age-related changes in the thymus of mature male Wistar rats developmentally exposed to the endocrine disruptor dichlorodiphenyltrichloroethane (DDT). The study was carried out at the stage of early thymus involution. Differences in the thymus morphology associated with imbalance of morphogenetic processes in the cortex and medulla were observed after puberty in rats developmentally exposed to DDT. Increased proliferation of thymocytes, higher content of lymphoblasts, and concomitant decrease in T-cell migration in comparison with the control were found. Our findings indicate lower functional maturity of the thymus and prolonged disorders in the program of postnatal thymus development induced by the endocrine disruptor DDT.

Quantitative structure activity relationship studies of androgen receptor binding affinity of endocrine disruptor chemicals with index of ideality of correlation, their molecular docking, molecular dynamics and ADME studies.

Endocrine disrupter chemicals (EDCs) are both natural and man-made chemicals that mimic, block or interfere with human hormonal system. In the present manuscript, QSAR modeling was performed for the androgen disruptors that interfere with biosynthesis, metabolism or action of androgens that causes adverse effects on male reproductive system. A set of 96 EDCs that exhibited affinity towards androgen receptors (Log RBA) in rats were employed for carrying out QSAR studies using Hybrid descriptors (combination of HFG and SMILES) through Monte Carlo Optimization. Using index of ideality of correlation (TF2), five splits were formed and predictability of five models resulting from these splits was assessed by various validation parameters. Models resulted from first split was the top most one with R2validation = 0.7878. Structural attributes responsible for change in endpoint were studied by employing correlation weights of structural attributes. In order to further validate the model, new EDCs were designed using these attributes. In silico molecular modelling studies were performed to assess the detailed interactions with the receptor. The binding energies of all the designed compounds were observed to be better than lead and are in the range of -10.46 to -14.80. Molecular dynamics simulation of 100 ns was performed for ED01 and NED05. The results revealed that the protein-ligand complex bearing NED05 was more stable than lead ED01 exhibiting better interactions with the receptor. Further, in an attempt to assess their metabolism, ADME studies were evaluated using SwissADME. The developed model enables to predict the characteristics of designed compounds in an authentic way.Communicated by Ramaswamy H. Sarma.

Awareness Regarding Sex Hormone Disruptors in Everyday Products Among Females of Reproductive Age in Al-Jouf, the Kingdom of Saudi Arabia.

Background and objective Endocrine-disrupting chemicals (EDCs) are natural or synthetic molecules that can alter and affect the operations of the hormonal system of an organism. These compounds include plastic consumer products and food containers such as phytoestrogen, which is also naturally present in food. EDCs can be found in the cord blood and maternal blood of pregnant women, as well as colostrum. Hence, they may affect not only the mother but also the offspring. In this study, we aimed to evaluate the awareness among females of reproductive age regarding the nature, source, as well as physiological and psychological burden associated with sex hormones disruptors. Methods A descriptive cross-sectional study was conducted among females between the age of 15-45 years in the Al-Jouf region, Saudi Arabia. A self-administrated questionnaire was used as the data collection tool; it consisted of multiple-choice questions to obtain information on the awareness among the females. In this study, females were classified into those with good knowledge and those with poor knowledge based on their level of knowledge by using a scoring system with a total score of 12. IBM SPSS Statistics version 24 (IBM Corp., Armonk, NY) was used to analyze the collected data. Results The study included 491 females; 6.6% of them had been using soya-containing products for a long time, and 32.5% reported using oatmeal for a long time. The majority (86.2%) did not use any other hormonal therapy. There were significant differences in the knowledge about sex hormone disruptors among the participants, and women with poorer knowledge about sex hormone disruptors were significantly less likely to report the long-time usage of soya-containing food when compared to women with greater knowledge (2.2% vs. 4.2%, p<0.001). The results showed that women with poorer knowledge were also significantly less likely to report the usage of hormonal therapies when compared to women with greater knowledge (6.7% vs. 7.2%, p<0.001), indicating that the usage of these chemicals is higher in women with greater knowledge although they are aware of their effects. Conclusion The study showed that females had good knowledge about the nature and usage of EDCs but poor knowledge about their impact. The knowledge of females was associated with their behavior regarding the usage of such products.

Long-term effect of PBDE-99 prenatal exposure on spermatogenic injuries via the dysregulation of autophagy.

Although it has been reported that perinatal, especially prenatal exposure to polybrominated diphenyl ethers (PBDEs) alters offspring's fertility, but little is known regarding their longitudinal effects over time. In the current study, we determined the associations between prenatal exposure to 2,2',4,4',5-pentabromodiphenyl ether (PBDE-99) of environmentally relevant levels in pregnant ICR mice and spermatogenic impairments in male offspring on postnatal day 70. Then, we monitored functional injuries in spermatogenic cells (GC-1 spg) exposed to PBDE-99 in vitro. Furthermore, transcriptome sequencing and bioinformatic analysis were used to investigate the underlying mechanism of PBDE-99 exposure to GC-1 spg. Additionally, the expression levels of key genes in the relevant pathways were quantified. Our findings indicated that exposure to PBDE-99 caused significantly spermatogenic injuries, which partly owing to the accumulation of reactive oxygen species, dysregulation of autophagy, and finally induced spermatogenic cell apoptosis. Rescue validation experiments showed that stimulating autophagy could alleviate spermatogenic cell injury induced by PBDE-99. In conclusion, our findings indicated that the dysfunction of autophagy played a significant role in long-term reproductive toxicity following prenatal exposure to environmental concentrations of PBDE-99.

Wild fish responses to wastewater treatment plant upgrades in the Grand River, Ontario.

Municipal wastewater treatment plant (WWTP) effluent is one of several point sources of contaminants (nutrients, pharmaceuticals, estrogens, etc.) which can lead to adverse responses in aquatic life. Studies of WWTP effluent impacts on rainbow darter (Etheostoma caeruleum) collected downstream of WWTPs in the Grand River, Ontario have reported disruption at multiple levels of biological organization, including altered vitellogenin gene expression, lower levels of in vitro steroid production, and high frequency of intersex. However, major upgrades have occurred at treatment plants in the central Grand River over the last decade. Treatment upgrades to the Waterloo WWTP were initiated in 2009 but due to construction delays, the upgrades came fully on-line in 2017/2018. Responses in rainbow darter have been followed at sites associated with the outfall consistently over this entire time period. The treatment plant upgrade resulted in nitrification of effluent, and once complete there was a major reduction in effluent ammonia, selected pharmaceuticals, and estrogenicity. This study compared several key responses in rainbow darter associated with the Waterloo WWTP outfall prior to and post upgrades. Stable isotopes signatures in fish were used to track exposure to effluent and changed dramatically over time, corresponding to the effluent quality. Disruptions in in vitro steroid production and intersex in the darters that had been identified prior to the upgrades were no longer statistically different from the upstream reference sites after the upgrades. Although annual variations in water temperature and flow can potentially mask or exacerbate the effects of the WWTP effluent, major capital investments in wastewater treatment targeted at improving effluent quality have corresponded with the reduction of adverse responses in fish in the receiving environment.

Effects of dioxins on animal spermatogenesis: A state-of-the-art review.

The male reproductive system is especially affected by dioxins, a group of persistent environmental pollutants, resulting in irreversible abnormalities including effects on sexual function and fertility in adult males and possibly on the development of male offspring. The reproductive toxicity caused by dioxins is mostly mediated by an aryl hydrocarbon receptor (AhR). In animals, spermatogenesis is a highly sensitive and dynamic process that includes proliferation and maturation of germ cells. Spermatogenesis is subject to multiple endogenous and exogenous regulatory factors, including a wide range of environmental toxicants such as dioxins. This review discusses the toxicological effects of dioxins on spermatogenesis and their relevance to male infertility. After a detailed categorization of the environmental contaminants affecting the spermatogenesis, the exposure pathways and bioavailability of dioxins in animals was briefly reviewed. The effects of dioxins on spermatogenesis are then outlined in detail. The endocrine-disrupting effects of dioxins in animals and humans are discussed with a particular focus on their effects on the expression of spermatogenesis-related genes. Finally, the impacts of dioxins on the ratio of X and Y chromosomes, the status of serum sex hormones, the quality and fertility of sperm, and the transgenerational effects of dioxins on male reproduction are reviewed.

New combination of pulsed light and iron (II) for carbonate radical production to enhanced degradation of bisphenol A: Parameter optimization and degradation pathway.

Bisphenol A(BPA) is a common industrial chemical with significant adverse impacts on Environment and human health. The present work evaluates the efficacy of pulsed light (PL) and Fe2+ ions in activation of sodium percarbonate (SPC) to produce hydroxyl (OH•) and carbonate (CO3•-) radicals for efficient degradation of BPA. The effects of operational parameters such as solution pH, SPC and Fe2+ dose as well as the mixture composition were analyzed and the decomposition pathway of BPA proposed. The BPA was successfully degraded at the initial concentration of 15.0 mg/L and optimized conditions by the PL/Fe2+/SPC process (99.67 ± 0.29%). A rapid reduction in the degradation of BPA was observed with increasing pH due to OH• radicals quenching and also the precipitation of Fe2+. Under the optimized conditions, degradation of BPA by PL/Fe2+/SPC process was five-times faster than the individual process. The quenching experiments revealed that radical and non-radical pathways on BPA degradation was accomplished with OH•, CO3•-, O2•-, and 1O2, while OH• and CO3•- radicals (as a dominant radicals) have the contributions of 80.23% and 8.30%, respectively. Based on the detected byproducts, ring cleavage can be considered as the main transformation mechanism of BPA by the PL/Fe2+/SPC process.

Toxicity alleviation and metabolism enhancement of nonylphenol in green algae Dictyosphaerium sp. by NaHCO3.

Nonylphenol (NP) toxicity limits the improvements in its algal remediation efficiency. This study comprehensively investigated the performance and mechanism of NaHCO3-driving effects on NP-exposed algae. The results showed that NaHCO3 enhanced algal resistance to NP and the corresponding EC50 values increased 1.31-4.25 times. Further, the toxicological effects of NP reduced with increasing pyrenoid volume and chlorophyll and carotenoids production, and decreasing cellular damage degree. Moreover, the concentration of extracellular polymeric substances was enhanced and more NP adsorption sites were formed. Consistently, RNA-seq demonstrated significant expression alterations in genes related to energy metabolism, cellular synthesis, photosynthesis, and carbon fixation. Besides, NP biodegradation rate was increased by 15.2 % and 11.1 % in the 1, and 4 mg/L NP treatments, respectively. Identification of degradation intermediates and their toxicity via Ecological Structure Activity Relationship program showed that NaHCO3 accelerated sequential α-C removal from NP in algae with faster generation of less toxic metabolites, namely, 4-ethylphenol, 4-cresol and 4-hydroxybenzoic acid. This study provides new insights into the role of NaHCO3 in toxicity alleviation and metabolism enhancement of NP in algae and can assist NP bioremediation efforts in aquatic environment.

Feasibility and potential of laccase-based enzyme in wastewater treatment through sustainable approach: A review.

The worldwide increase in metropolitan cities and rise in industrialization have resulted in the assimilation of hazardous pollutants into the ecosystems. Different physical, chemical and biological techniques have been employed to remove these toxins from water bodies. Several bioprocess applications using microbes and their enzymes are utilized to achieve the goal. Biocatalysts, such as laccases, are employed explicitly to deplete a variety of organic pollutants. However, the degradation of contaminants using biocatalysts has many disadvantages concerning the stability and activity of the enzyme. Hence, they are immobilized on different supports to improve the enzyme kinetics and recyclability. Furthermore, standard wastewater treatment methods are not effective in eliminating all the contaminants. As a result, membrane separation technologies have emerged to overcome the limitations of traditional wastewater treatment methods. Moreover, enzymes immobilized onto these membranes have generated new avenues in wastewater purification technology. This review provides the latest information on laccases from diverse sources, their molecular framework and their mode of action. This report also gives information about various immobilization techniques and the application of membrane bioreactors to eliminate and biotransform hazardous contaminants. In a nutshell, laccases appear to be the most promising biocatalysts for green and cost-efficient wastewater treatment technologies.

Assessment of endocrine disruptive properties of PFOS: EFSA/ECHA guidance case study utilising AOP networks and alternative methods.

Endocrine disruptors (EDs) are chemical substances that interfere with the endocrine system, adversely affecting human health and environment. Legislation with aim to eliminate and ban EDs have been introduced in EU, but the identification of EDs remains challenging and crucial step towards regulation and risk management. A guidance for ED assessment has been recently established for pesticides and biocides in the EU, which heavily relies on traditional toxicological testing in vivo. Most notably lacking mechanistic methods for some ED modalities and not covering many other modalities that might be affected by EDs. In this project, we focus on the ED assessment according to the valid legislation and explore the possibility to employ alternative methods to bolster the mechanistic understanding of the ED effects and eventually decrease the need for in vivo testing. We selected a well-studied industrial chemical perfluorooctanesulfonic acid (PFOS) to be a model compound in a case study for ED assessment where the EU criteria were applied in the frame of human health risk assessment with focus on thyroid disruption and developmental neurotoxicity. A systematic literature review has been conducted for these effects (Scopus, Pubmed, Embase), and relevant studies were selected by title/abstract screening (RAYYAN) and full-text examination. Selected studies were assessed for reliability (SciRAP), and all relevant data were extracted into a database and assessed by Weight of Evidence (WoE) approach. The initial analysis showed potential endocrine adverse effects and endocrine activity, meeting the ED criteria. The use of mechanistic and alternative methods enhanced the outcomes of WoE assessment. Also, the study provides a great hands-on experience with the most up-to-date development in the area of risk assessment and EDs.

Effect of BPA on CYP450s expression, and nicotine modulation, in fetal rat brain.

Human exposure to bisphenol A (BPA) is mainly due to migration from plastic packaging into food and beverages. Studies reported BPA endocrine disruptions through interactions with different nuclear receptors, including the arylhydrocarbon receptor (AhR). AhR mediates xenobiotic responses and regulates expression of drug-metabolizing enzymes (DMEs), including many CYP450s. This study aimed to assess the effects of BPA maternal exposure on CYP450s expression in fetal brain. Sprague-Dawley dams were exposed to BPA concentrations of 0, 0.5, 5, and 50 mg/L in drinking water, individually, and with nicotine. Fetal brains were isolated at gestational days GD14 and GD19, and protein expression was assessed by Western blotting. Results showed a BPA-induced significant decrease in CYP1B1 expression levels at GD14 (p = 0.001), and CYP19A1 (aromatase) expression at both mid- and late-stage development (p < 0.001). In addition, nicotine individually decreased expression levels of all examined protein targets, significantly for CYP1B1 (p < 0.001), CYP19A1 (p = 0.010), AhRR (p = 0.042), and ARNT (p < 0.001), compared to control. When combined with BPA, nicotine suppressive effects were attenuated at both GD14 and GD19. In conclusion, BPA suppresses CYP1B1 and CYP19A1 expression in fetal brain, and attenuates the suppressive effects of nicotine. Observed effects may be mediated by AhR-ARNT independent mechanisms that need further examination.

The effect of nonylphenol exposure on the stimulation of melanomacrophage centers, estrogen and testosterone level, and ERα gene expression in goldfish.

The present study tried to measure the formation of melanomacrophage centers (MMCs) in various organs of male and female goldfish exposed to nonylphenol (NP) and aimed to assess its relationship with the main sexual hormones, estrogen receptor expression, and the pigment content of the MMCs. Immature goldfish were exposed to 10-6 and 10-7 M NP for 25 days. After obtaining blood for measuring testosterone and estrogen (E2) levels, tissue samples were collected from various organs for histological studies, quantifying pigments using ImageJ software and chemical analysis, and measuring ERα gene expression. Results showed that the order of forming MMCs in various organs exposed to NP was liver > spleen > kidney, and the order of ERα gene expression was liver > testes > spleen > kidney in the male, and liver > spleen > kidney > ovaries in the female. Among the three pigments present in MMCs after exposure to the two doses of NP, melanin was more obvious (especially in the liver) and increased mostly in a dose-dependent manner in both sexes (especially in the male). Chemical analyses confirmed these results. Measurement of testosterone and E2 level in male and female goldfish showed that NP had more effect on the concentration of these hormones in male fish, indicating more endocrine-disrupting potential of NP against the male fish. Generally, the increase of melanin content of melanomacrophage centers coincided with the increase of ERα gene expression and decrease of testosterone level in goldfish after exposure to NP.