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Journal of Hazardous Materials Aug 2023The broad utilization of betamethasone in medical treatments may pose a significant ecotoxicological risk to aquatic organisms, yet its potential reproductive toxicity...
The broad utilization of betamethasone in medical treatments may pose a significant ecotoxicological risk to aquatic organisms, yet its potential reproductive toxicity remains unclear. The present study examined the impacts of environmental exposure on male reproduction using Japanese medaka (Oryzias latipes). After 110 days of betamethasone exposure at environmentally relevant concentrations (0, 20 and 200 ng/L), LH/FSH synthesis and release in the pituitary was inhibited, and the production of sex hormones and their signaling pathways in the gonads of male medaka were greatly influenced. This synthetic glucocorticoid restrained testosterone (T) synthesis and gave rise to a significant increase in E/T and E/11-KT ratios. Furthermore, chronic betamethasone exposure (20 and 200 ng/L) led to the suppression of androgen receptor (AR) signaling and enhancement of estrogen receptors (ERs) signaling. An increase in hepatic vitellogenin contents was also detected, and testicular oocytes were observed in both 20 and 200 ng/L betamethasone-treated groups. It showed that 20 and 200 ng/L betamethasone could induce male feminization and even intersex, triggering abnormal spermatogenesis in medaka males. With its adverse effects on male fertility, betamethasone could potentially influence the fishery productivity and population dynamics in aquatic ecosystems.
Topics: Animals; Male; Oryzias; Betamethasone; Ecosystem; Gonads; Reproduction; Disorders of Sex Development; Water Pollutants, Chemical
PubMed: 37156043
DOI: 10.1016/j.jhazmat.2023.131493 -
Environmental Toxicology and Chemistry Dec 2023The US Environmental Protection Agency (USEPA) is faced with long lists of chemicals that require hazard assessment. The present study is part of a larger effort to...
The US Environmental Protection Agency (USEPA) is faced with long lists of chemicals that require hazard assessment. The present study is part of a larger effort to develop in vitro assays and quantitative structure-activity relationships applicable to untested chemicals on USEPA inventories through study of estrogen receptor (ER) binding and estrogen-mediated gene expression in fish. The present effort investigates metabolic activation of chemicals resulting in increased estrogenicity. Phenolphthalin (PLIN) was shown not to bind rainbow trout (Oncorhynchus mykiss) ER (rtER) in a competitive binding assay, but vitellogenin (Vtg) expression was induced in trout liver slices exposed to 10 and 10 M PLIN. Phenolphthalein (PLEIN), a metabolite of PLIN, was subsequently determined to be formed when slices were exposed to PLIN. It binds rtER with a relative binding affinity to 17β-estradiol of 0.020%. Slices exposed to PLEIN expressed Vtg messenger RNA (mRNA) at 10 , 10 , and 10 M, with no detectable PLIN present. Thus, Vtg expression noted in PLIN slice exposures was explained by metabolism to PLEIN in trout liver slices. A second model chemical, 4,4'-methylenedianiline (MDA), was not shown to bind rtER but did induce Vtg mRNA production in tissue slices at 10 , 10 , and 10 M in amounts nearly equal to reference estradiol induction, thus indicating metabolic activation of MDA. A series of experiments were performed to identify a potential metabolite responsible for the observed increase in activity. Potential metabolites hydroxylamine-MDA, nitroso-MDA, azo-MDA, and azoxy-MDA were not observed. However, acetylated MDA was observed and tested in both ER-binding and tissue slice Vtg induction assays. Environ Toxicol Chem 2023;42:2747-2757. © 2023 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Topics: Humans; Animals; Activation, Metabolic; Xenobiotics; Estradiol; Vitellogenins; Oncorhynchus mykiss; RNA, Messenger
PubMed: 37712519
DOI: 10.1002/etc.5748 -
Frontiers in Endocrinology 2023Bursicon, a neuropeptide hormone comprising two subunits-bursicon (burs) and partner of burs (pburs), belongs to the cystine-knot protein family. Bursicon heterodimers...
Bursicon, a neuropeptide hormone comprising two subunits-bursicon (burs) and partner of burs (pburs), belongs to the cystine-knot protein family. Bursicon heterodimers and homodimers bind to the lucine-rich G-protein coupled receptor (LGR) encoded by s to regulate multiple physiological processes in arthropods. Notably, these processes encompass the regulation of female reproduction, a recent revelation in . In this study we investigated the role of burs/pburs/rickets in mediating female vitellogenesis and reproduction in a hemipteran insect, the whitefly, . Our investigation unveiled a synchronized expression of and , with their transcripts persisting detectable in the days following eclosion. RNAi-mediated knockdown of , or significantly suppressed the transcript levels of () and in the female whiteflies. These effects also impaired ovarian maturation and female fecundity, as evidenced by a reduction in the number of eggs laid per female, a decrease in egg size and a decline in egg hatching rate. Furthermore, knockdown of , or led to diminished juvenile hormone (JH) titers and reduced transcript level of . However, this impact did not extend to genes in the insulin pathway or target of rapamycin pathway, deviating from the results observed in . Taken together, we conclude that burs/pburs/rickets regulates the vitellogenesis and reproduction in the whiteflies by coordinating with the JH signaling pathway.
Topics: Animals; Female; Hemiptera; Invertebrate Hormones; Juvenile Hormones; Vitellogenesis; Neuropeptides; Rickets
PubMed: 37854192
DOI: 10.3389/fendo.2023.1277439 -
The Science of the Total Environment Aug 2023Neonicotinoids are among the most widely used insecticides in the world and are recognized as a potential cause of pollinator decline. Previous studies have demonstrated...
Neonicotinoids are among the most widely used insecticides in the world and are recognized as a potential cause of pollinator decline. Previous studies have demonstrated that the neonicotinoid thiacloprid has adverse effects on foraging and memory behaviors. However, there is no direct evidence linking thiacloprid-induced neuronal cell damage in the brains of honeybees to learning and memory dysfunction. Adult honeybee (Apis mellifera L.) workers were chronically exposed to sub-lethal concentrations of thiacloprid. We discovered that thiacloprid negatively affected their survival, food consumption, and body weight. In addition, sucrose sensitivity and memory performance were impaired. We evaluated the apoptosis of honeybee brain cells using TUNEL (Terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling) and Caspase-3 assays, which revealed that thiacloprid increases the dose-dependent apoptosis of neurons in the mushroom bodies (MB) and antennal lobes (AL). We also determined the abnormal transcripts of multiple genes, including vitellogenin (Vg), immune system genes (apidaecin and catalase), and memory-associated genes (pka, creb, Nmdar1, Dop2, Oa1, Oa-2R, and Oa-3R). These results indicate that exposure to sublethal concentrations of thiacloprid cause abnormal expression of memory-related genes and apoptosis of brain cells in the AL and MB, which may contribute to the memory disorder induced by thiacloprid exposure.
Topics: Bees; Animals; Neonicotinoids; Learning; Insecticides; Apoptosis
PubMed: 37142029
DOI: 10.1016/j.scitotenv.2023.163820 -
Journal of Xenobiotics Feb 2024Pyriproxyfen is an insecticide currently employed in numerous countries for the management of agricultural and indoor pests. Several studies indicate that this...
Pyriproxyfen is an insecticide currently employed in numerous countries for the management of agricultural and indoor pests. Several studies indicate that this insecticide has been detected in multiple rivers, with concentrations reaching as high as 99.59 ng/L in the Júcar River in Spain. Therefore, the determination of some biochemical and genetic effects of this insecticide on aquatic organisms could serve as an early warning mechanism to identify potential disruptions in various biomarkers. Based on this, organisms were exposed to pyriproxyfen sublethal concentrations for 21 days. Some biochemical parameters, including cholesterol, triglycerides, glucose, lactate, and LDH activity, were determined. Additionally, some genetic biomarkers associated with oxidative stress, heat shock proteins, lipid metabolism, hemoglobin, metallothioneins, and vitellogenin synthesis were evaluated in daphnids exposed to the insecticide for 21 days. LDH activity increased significantly in those daphnids exposed to the highest insecticide concentration (14.02 µg/L), while cholesterol levels decreased significantly. In contrast, glucose, total proteins, and triglycerides remained unaffected in exposed to pyriproxyfen. On the other hand, exposure to the insecticide led to notable alterations in gene expression among individuals. Specifically, genes associated with lipid metabolism and reproduction exhibited a significant reduction in gene expression. F expression was decreased by approximately 20% in exposed daphnids, while expression was suppressed as much as 80% when compared to control values. Furthermore, it was observed that the and genes, associated with hemoglobin synthesis, exhibited significant overexpression. Notably, the dysfunction observed in both hemoglobin genes was linked to an increase in pigmentation in during the course of the experiment. These alterations in gene expression could serve as effective indicators of early contamination even at low pesticide concentrations.
PubMed: 38390993
DOI: 10.3390/jox14010013 -
Journal of Toxicology and Environmental... Oct 2023In applying bioanalytical approaches, the aim of this study was to determine the toxicity of contaminants derived from a solid waste dumpsite in Calabar (Nigeria), by...
A bioanalytical approach for assessing the effects of soil extracts from solid waste dumpsite in Calabar (Nigeria) on lipid and estrogenic signaling of fish hepatocellular carcinoma-1 cells and African catfish ().
In applying bioanalytical approaches, the aim of this study was to determine the toxicity of contaminants derived from a solid waste dumpsite in Calabar (Nigeria), by investigating the alterations of lipid and estrogen signaling pathways in hepatocellular carcinoma-1 (PLHC-1) cells and compared to African catfish (), using polar, nonpolar and elutriate extraction methods. Cells were exposed for 48 hr period to different concentrations of the contaminant extracts. The PLHC-1 cells were evaluated for lipid responses as follows adipoRed assay, retinoid x receptor (), peroxisome proliferator-activated receptor isoforms (-α and γ), estrogen receptor (-α) and vitellogenin () transcripts. The lipid signaling activation was also assessed in using , where hepatic levels of -α were determined at both transcript and functional proteins levels. Data showed variable-, extract type and concentration-specific elevations in mRNA and protein levels for lipidomic and estrogenic effects. These effects were either biphasic at low and high concentrations, depending upon extract type, or concentration-dependent elevations. In general, these toxicological responses may be attributed to soil organic and inorganic contaminants burden previously derived from the dumpsite. Thus, our data demonstrate a unique lipid and endocrine-disruptive chemical (EDC) effects of each soil extract, suggesting multiple and complex contaminant interactions in the environment and biota. Analysis of numerous soil- or sediment-bound contaminants have numerous limitations and cost implications for developing countries. Our approach provides a bioanalytical protocol and endpoints for measuring the metabolic and EDC effects of complex environmental matrices for ecotoxicological assessment and monitoring.
Topics: Animals; Catfishes; Carcinoma, Hepatocellular; Solid Waste; Soil; Nigeria; Peroxisome Proliferator-Activated Receptors; Water Pollutants, Chemical; Liver Neoplasms; Lipids
PubMed: 37504673
DOI: 10.1080/15287394.2023.2240839 -
Environmental Toxicology and Chemistry Apr 2024Understanding species differences in sensitivity to toxicants is a critical issue in ecotoxicology. We recently established that double-crested cormorant (DCCO) embryos...
Understanding species differences in sensitivity to toxicants is a critical issue in ecotoxicology. We recently established that double-crested cormorant (DCCO) embryos are more sensitive than Japanese quail (JQ) to the developmental effects of ethinylestradiol (EE2). We explored how this difference in sensitivity between species is reflected at a transcriptomic level. The EE2 was dissolved in dimethyl sulfoxide and injected into the air cell of eggs prior to incubation at nominal concentrations of 0, 3.33, and 33.3 µg/g egg weight. At midincubation (JQ 9 days; DCCO 16 days), livers were collected from five embryos/treatment group for RNA sequencing. Data were processed and analyzed using EcoOmicsAnalyst and ExpressAnalyst. The EE2 exposure dysregulated 238 and 1,987 genes in JQ and DCCO, respectively, with 78 genes in common between the two species. These included classic biomarkers of estrogen exposure such as vitellogenin and apovitellenin. We also report DCCO-specific dysregulation of Phase I/II enzyme-coding genes and species-specific transcriptional ontogeny of vitellogenin-2. Twelve Kyoto Encyclopedia of Genes and Genomes pathways and two EcoToxModules were dysregulated in common in both species including the peroxisome proliferator-activated receptor (PPAR) signaling pathway and fatty acid metabolism. Similar to previously reported differences at the organismal level, DCCO were more responsive to EE2 exposure than JQ at the gene expression level. Our description of differences in transcriptional responses to EE2 in early life stage birds may contribute to a better understanding of the molecular basis for species differences. Environ Toxicol Chem 2024;43:772-783. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Topics: Animals; Ethinyl Estradiol; Coturnix; Vitellogenins; Gene Expression Profiling; Liver
PubMed: 38116984
DOI: 10.1002/etc.5811 -
Biochemical and Biophysical Research... Oct 2023Vitellogenin (Vtg) serves as the precursor of yolk protein and exhibits widespread distribution in tissues, including in the ovary of both vertebrates and invertebrates....
Vitellogenin (Vtg) serves as the precursor of yolk protein and exhibits widespread distribution in tissues, including in the ovary of both vertebrates and invertebrates. Vtg plays a critical role in facilitating oocyte maturation and embryonic development following oviposition. In this study, we have successfully elucidated the complete transcript sequence of TtVtg6-like from an ancient chelicerate Tachypleus tridentatus. The TtVtg6-like transcript encompassed a length of 4887 bp and encoded 1629 amino acids residues. Notably, TtVtg6-like was found to contain 25 exons. Furthermore, the molecular weight and isoelectric point of TtVtg6-like were determined to be 191.6 KDa and 6.73, respectively. Subsequent mRNA expression analysis demonstrated the specific expression of TtVtg6-like in ovary and yellow connective tissue. In addition, TtVtg6-like was located and distributed in both ovary and yellow connective tissue. Intriguingly, employing an siRNA approach to silence TtVtg6-like resulted in a decrease in TtVtg6-like transcription levels. Concomitantly, TtVtg6-like silencing led to increase production of ROS, ultimately resulting in DNA damage and cell apoptosis within the ovarian primary cell. The induction of apoptosis ovarian primary cells due to TtVtg6-like silencing was further corroborated through TUNEL assay and flow cytometry analysis. Overall, our findings underscore the significance of TtVtg6-like in ovarian cell development, revealing its potential association with ovarian cell apoptosis. Consequently, the insights gained from this study contribute to the future exploration of vitellogenesis and ovarian development in T. tridentatus.
PubMed: 37673004
DOI: 10.1016/j.bbrc.2023.08.066 -
Integrated Environmental Assessment and... May 2024There has been increasing interest in endocrine-disrupting chemicals (EDCs) among scientists and public authorities over the last 30 years, notably because of their wide...
There has been increasing interest in endocrine-disrupting chemicals (EDCs) among scientists and public authorities over the last 30 years, notably because of their wide use and the increasing evidence of detrimental effects on humans and the environment. However, test systems for the detection of potential EDCs as well as testing strategies still require optimization. Thus, the aim of the present project was the development of an integrated test protocol that merges the existing OECD test guidelines (TGs) 229 (fish short-term reproduction assay) and 234 (fish sexual development test) and implements thyroid-related endpoints for fish. The integrated fish endocrine disruptor test (iFEDT) represents a comprehensive approach for fish testing, which covers reproduction, early development, and sexual differentiation, and will thus allow the identification of multiple endocrine-disruptive effects in fish. Using zebrafish (Danio rerio) as a model organism, two exposure tests were performed with well-studied EDCs: 6-propyl-2-thiouracil (PTU), an inhibitor of thyroid hormone synthesis, and 17α-ethinylestradiol (EE2), an estrogen receptor agonist. In part A of this article, the effects of PTU and EE2 on established endpoints of the two existing TGs are reported, whereas part B focuses on the novel thyroid-related endpoints. Results of part A document that, as expected, both PTU and EE2 had strong effects on various endocrine-related endpoints in zebrafish and their offspring. Merging of TGs 229 and 234 proved feasible, and all established biomarkers and endpoints were responsive as expected, including reproductive and morphometric changes (PTU and EE2), vitellogenin levels, sex ratio, gonad maturation, and histopathology (only for EE2) of different life stages. A validation of the iFEDT with other well-known EDCs will allow verification of the sensitivity and usability and confirm its capacity to improve the existing testing strategy for EDCs in fish. Integr Environ Assess Manag 2024;20:817-829. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
Topics: Animals; Humans; Zebrafish; Endocrine Disruptors; Ethinyl Estradiol; Sexual Development; Reproduction; Water Pollutants, Chemical
PubMed: 37483114
DOI: 10.1002/ieam.4819 -
Regulatory Toxicology and Pharmacology... Dec 2023Vitellogenin (VTG) is a biomarker for possible endocrine activity of chemicals acting via the estrogen, androgen, or steroidogenesis pathways. VTG is assessed in...
Vitellogenin (VTG) is a biomarker for possible endocrine activity of chemicals acting via the estrogen, androgen, or steroidogenesis pathways. VTG is assessed in standardised fish guideline studies conducted for regulatory safety assessment of chemicals. VTG data can be highly variable leading to concerns for potential equivocal, false positive and/or negative outcomes. Consequently, additional fish testing may be required to address uncertainties in the VTG response, and possibly erroneous/missed identification of endocrine activity. To better understand the technical challenges of VTG assessment and reporting for regulatory purposes, a survey was sent to 27 testing laboratories performing these analyses. The survey results from 16 respondents (6 from the UK, 3 from the USA, and 7 from the EU) were analysed and discussed in a follow-up webinar. High variability in background VTG concentrations was widely acknowledged and thought to be associated with fish batch, husbandry, laboratory practices, and several methodological aspects. These include sample collection and storage, VTG quantification, data handling, and the benchmarks used for data acceptability. Information gathered in the survey provides a basis for improving and harmonizing the measurement of VTG in fish, and an opportunity to reassess the suitability of current acceptability criteria in test guidelines.
Topics: Animals; Vitellogenins; Laboratories; Fishes; Estrogens; Endocrine System; Water Pollutants, Chemical
PubMed: 37820895
DOI: 10.1016/j.yrtph.2023.105501