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Enzymes involved in estrogen hydroxylations. Catechol estrogens can undergo methylation by catechol O-methyltransferase (COMT), and all hydroxyl groups can be conjugated to glucuronide or sulfate.
Source publication
Environmental contaminants can potentially disrupt endocrine processes by inter- fering with the function of enzymes involved in steroid synthesis and metabolism. Such in- terferences may result in reproductive problems, cancers, and toxicities related to (sexual) differentiation, growth, and development. Various known or suspected endocrine disrup...
Citations
... (Sanderson 2006). The environmental stressors can disrupt endocrine processes by affecting enzymes involved in steroid hormone synthesis and metabolism (Sanderson and Berg 2003). In an earlier study, triadimefon toxicity was assessed in zebrafish, which showed AhR2 and PXR receptor activation altered steroid metabolism, leading to sex-specific effects. ...
Monocrotophos (MCP), an organophosphate insecticide commonly used in agriculture, has raised concerns due to its runoff into aquatic ecosystems and causes potential adverse effects on fish. The present study envisaged the understanding of the impact of MCP on the ovarian tissues of Anabas testudineus (climbing perch), an air-breathing food fish often found close to agricultural fields, making it a valuable bio-indicator of agrochemical contamination. Transcriptome profiling of ovarian tissues in response to 45 days of MCP exposure at sub-lethal concentrations was performed. Using Illumina platform sequencing, a total of 144.51 million reads were produced. After filtering and trimming, 138.82 million high-quality reads were obtained, of which 96.10% were mapped to the Anabas genome. Expression analysis revealed a total of 54 significant differentially expressed genes (DEGs), including 28 upregulated genes, and 26 downregulated genes compared to the control group (Log2 FC > ± 1 and, adjusted p-value < 0.05). Gene ontology analysis of the DEGs revealed associations with molecular, biological, and cellular functions. Key detoxification genes, such as glutathione S-transferase and UDP-glucuronosyltransferase, were significantly upregulated, indicating an enhanced detoxification response to MCP. In contrast, cytochrome P450 family 1 subfamily A (cyp1a1), a gene critical for steroid hormone metabolism, was downregulated, suggesting disruptions in hormone regulation. Functional enrichment analysis highlighted several affected processes, including steroid hormone biosynthesis, oocyte meiosis, apoptosis, and progesterone-mediated oocyte maturation. The randomly selected eight DEGs using RT-qPCR confirmed consistent gene expression levels in line with the transcriptome data. This work identified significant genes associated with detoxification and reproduction events in the ovarian tissues for maintaining homeostasis. This will also serve as valuable information for further investigation of the association of the identified genes with the reproductive biology of fish in response to toxicants or pollutants.
... Cholesterol is a precursor to steroid hormones (Hung et al., 2016), and certain xenobiotics disrupt sex-hormone synthesis by impacting the levels of cholesterol (Danzo, 1997;Sanderson and van den Berg, 2003;Miller, 2017). We investigated how altered hormone levels affected the steroidogenic pathway following NIC treatment. ...
... Nakajima et al., 2006) Dichlorodiphenyltrichloroethane(DDT) Aromatase inhibition (Sanderson and van denSanderson and van den Berg, 2003) Reproductive(Cooper et al., 2002) Immune(Eskenazi et al., 2009) Neurobehavioral (Ribas-Fitó et al., 2003 Bisphenol A (BPA) ER activation/inhibition(Kurosawa et al., 2002) Reproductive(Hiroi et al., 2004) Immune(Rees Clayton et al., 2011) Neurobehavioral(Stacy et al., 2017) Phthalates ER activation(Mankidy et al., 2013) Reproductive(Colón et al., 2000) Immune(Robinson and Miller, 2015) Neurobehavioral(Zhang et al., 2019b) Phytoestrogens ...
... Endocrine disruptors (EDs) can strongly affect reproductive and endocrine functions in several ways, either by directly affecting hormone production through the interaction with appropriate enzymes, or through interfering with their transport to target organs to alter the natural hormone metabolism or even inactivating the function of steroidogenesis regulatory proteins (Sanderson and van den Berg, 2003). ...
The aim of this in vitro study was to examine the dose-dependent effects of iron as a potential endocrine disruptor in relation to the release of sexual steroid hormones by a human adrenocortical carcinoma (NCI-H295R) cell line. The cells were exposed to different concentrations (3.90, 62.50, 250, 500, 1000 μM) of FeSO4.7H2O and compared with the control group (culture medium without FeSO4.7H2O). Cell viability was measured by the metabolic activity assay. Quantification of sexual steroid production was performed by enzyme-linked immunosorbent assay. Following 48 h culture of the cells in the presence of FeSO4.7H2O, significantly (P < 0.001) increased production of progesterone was observed at the lowest concentration (3.90 μM) of FeSO4.7H2O, whereas the lowest release of progesterone by NCIH295R cells was noted after addition of 1000 μM of FeSO4.7H2O, which did not elicit cytotoxic action (P > 0.05). Testosterone production was substantially increased at the concentrations ≤ 62.50 μM of FeSO4.7H2O. Lower levels of testosterone were recorded in the groups with higher concentrations (≥ 250 μM) of FeSO4.7H2O (P > 0.05). The presented data suggest that iron has no endocrine disruptive effect on the release of sexual steroid hormones, but its toxicity may be reflected at other points of the steroidogenesis pathway.
... The obtained data suggest that the synergistic action of Zearalenone and the T-2 toxin is observed in the case of the predominance of the respiration processes in the presence of glycerol. Indirectly, this hypothesis is confirmed by previous literature data that describe the competitive binding of Zearalenone to the receptors of hormones of the cells (López-Fernández et al., 2007), and by the information that estrogen-like effect of Zearalenone may be associated with the increased activity of aromatase which transforms androgens into estrogens (Sanderson and van den Berg, 2003). ...
... [2] These can directly affect hormone production by interacting with the enzymes, to interfere with their transport to target organs, to alter natural hormone metabolism, or to inactivate the function of steroidogenesis regulatory proteins (e.g., Steroidogenic Acute Regulatory -StAR). [3] In exposed organisms, environmental contaminants such as pesticides, pollutants, heavy or transition metals, [1,[4][5][6][7][8] and other industrial chemicals such as, alkylphenols, [9][10][11][12] polychlorinated biphenyls [13] and bisphenol A [14][15] may jeopardize proper endocrine functions, [1] including adverse effects on their reproductive system. Copper (Cu) is an essential trace element [16][17] and plays important roles in various physiological, enzymatic and regulatory processes. ...
... [59,68] Although characterized by a lower sensitivity to cytotoxicity in comparison to other cell lines, NCI-H295R is an effective screening toll for identification of chemical substances affecting biosynthesis of steroid hormones. [3,65,70] In fact, the NCI-H295R Steroidogenesis Assays has been included in the Tier1 Screening Battery of the United States Environmental Protection Agency's (EPA) Endocrine Disruptor Screening Program (EDSP). The test guideline of the H295R Steroidogenesis Assay (TG 456) has been further validated by the Organization for Economic Cooperation and Development (OECD). ...
Copper is an environmental risk factor, which has various effects on reproductive endocrinology. In this study human adrenocortical carcinoma (NCI-H295R) cell line was used as an in vitro biological model to study the effect of copper sulfate (CuSO4.5H2O) on steroidogenesis and cytotoxicity. The cell cultures were exposed to different concentrations (3.90, 62.50, 250, 500, 1000 µM) of CuSO4.5H2O and compared to control group (medium without CuSO4.5H2O). Cell viability was measured by the metabolic activity assay. Quantification of sexual steroid production directly from the medium was performed by ELISA assay. Following 48 h culture of NCI-H295R cell line in the presence of CuSO4.5H2O a dose-dependent depletion of progesterone release was observed even at the lower concentrations of CuSO4.5H2O. The lowest levels of progesterone were detected in groups with the higher doses (≥ 250 µM) of CuSO4.5H2O, which elicited significant cytotoxic action. Testosterone production decreased significantly, and this decline was more prominent in comparison to that of progesterone. The lowest release of testosterone was recorded at 1000 µM of CuSO4.5H2O. The cytotoxic effect of CuSO4.5H2O was evident at all concentrations used in the study. The presented data suggest that copper has detrimental effects on sexual steroid hormones and consecutively on reproductive physiology.
... Hu et al., 2014;Mesnage et al., 2018). HSD11B2 and HSD3B1 are important for the steroid hormone biosynthesis pathway (Table 2), a major cascade targeted by industrial chemicals (Sanderson, 2006;Sanderson and van den Berg, 2003). ...
The liver is one of the major targets of hormones, including thyroid hormones (THs), and many industrial chemicals, such as endocrine-disrupting chemicals. Those compounds may permeate the placenta barrier and pose a risk for embryonic development. Therefore, it is necessary to assess the toxic effects of those kind of industrial chemicals during liver development. In this study, to mimic liver specification in vitro, we differentiated human embryonic stem cells (ESCs) into functional hepatocyte-like cells. We performed this differentiation process in presence of two THs, triiodothyronine (T3) and thyroxine (T4), with the purpose of identifying biomarkers for toxicity screening. TH exposure (3, 30 and 300 nM) yielded to hepatocytes with impaired glycogen storage ability and abnormal lipid droplets’ accumulation. Global gene expression analysis by RNA-seq identified a number of genes responsible for hepatic differentiation and function which were affected by 30 nM T3 and T4. Those differentially expressed genes were used to assess the potential developmental liver toxicity of two famous environmental pollutants, 2, 2, 4, 4-tetrabromodiphenyl ether (BDE-47) and decabromodiphenyl ether (BDE-209), at 10 nM to 1 μM treatments. Our findings demonstrate that BDE-47 and BDE-209, dysregulated pathways such as “chemical carcinogenesis”, “steroid hormone biosynthesis” and “drug metabolism-cytochrome P450”. Moreover, we were able to identify a set of 17 biomarkers, very useful to predict the potential developmental hepatotoxicity of industrial chemicals.
... Vitellogenesis can be affected by xenobiotics; in our data, females exposed to sediments from Urias 3 showed the lowest levels of Vtg expression. Some mechanisms of vitellogenesis disruption have been reported, for instance, the binding of xenobiotics to the estrogen receptor (ER) activating transcription of estrogen-responsive genes (Bowman et al. 2000, Pan et al. 2017; or altering steroid hormone synthesis and metabolism through specific interactions with key enzymes, such as the cytochrome P450 (CYP) superfamily (Sanderson and van den Berg 2003). Several compounds such as pesticides, fungicides, triazines, PAHs, and industrial chemicals are able to interfere with CYP action during steroidogenesis, thus blocking steroid hormone synthesis. ...
Context: Fiddler crabs are important to the ecology of estuarine systems around the world, however few studies have incorporated them as bioindicators. Urias estuary represents one of the most urbanized lagoons in the Gulf of California region and received discharges from different sources: shrimp farm, thermoelectric plant, fish processing plants, and untreated domestic and sewage wastes.
Objective: Assess the effects on anthropogenic contamination on female fiddler crabs reproduction, survival, and genetic stability.
Methods: Exposition of wild crabs from a less impacted (reference) site to naturally contaminated sediments on under controlled laboratory conditions. Reproductive parameters, levels of DNA damage and mortality rates were measured, together with chemical analyses of sediments.
Results: The most contaminated sediments corresponded to the site where fish processing plants were located and the integrated biomarker response analysis revealed that the most adverse effects were produced by exposure to sediments from this site; these crabs showed higher mortality (67%) and poorer ovarian development than those crabs exposed to sediments from other sites.
Conclusions: Female crabs under pollution stress are able to trade-off reproduction for survival, and surviving animals were able to restore genetic stability possibly by activating DNA repair mechanisms. Multiple biomarker approach discriminates different coastal contamination scenarios.
... P450s catalyse the reductive scission of molecular oxygen and are responsible for the synthesis and metabolism of various molecules, including drugs, hormones, antibiotics, pesticides, carcinogens and toxins [61]. The hormones they synthesize, such as glucocorticoids, mineralocorticoids, progestins, and sex hormones, are critical to stress response, growth and reproduction, and the endogenous and exogenous chemical metabolism participate in combatting toxic compounds [62]. ...
Background
The golden apple snail (Pomacea canaliculata) is a fresh water snail listed among the top-100 worst invasive species worldwide and a noted agricultural and quarantine pest that causes great economic losses. It is characterized by fast growth, strong stress tolerance, a high reproduction rate, and adaptation to a broad range of environments.
Results
Here, we used long-read sequencing to produce a 440-Mb high-quality, chromosome-level assembly of the P. canaliculata genome. In total, 50 Mb (11.4%) repeat sequences and 21,533 gene models were identified in the genome. The major findings of this study include the recent explosion of DNA/hAT-Charlie transposable elements (TEs), the expansion of the P450 gene family and the constitution of the cellular homeostasis system, which contributes to ecological plasticity in stress adaptation. In addition, the high transcriptional levels of perivitellin genes in the ovary and albumen gland promote the function of nutrient supply and defence ability in eggs. Furthermore, the gut metagenome also contains diverse genes for food digestion and xenobiotic degradation.
Conclusions
These findings collectively provide novel insights into the molecular mechanisms of the ecological plasticity and high invasiveness.
... Toxicological effects of OTs both in vitro and in vivo have been documented and the imposex and masculinization of female gastropod appeared to be the main biological impact to marine organisms (Cima and Ballarin, 2012;Graceli et al., 2013;Pagliarani et al., 2013). As endocrine-disrupting chemicals (EDC), OTs induce alteration in expression of hormones and activity of steroidogenic enzymes and steroid receptors span from the aquatic species to terrestrial organisms (Kopp et al., 2017;McGinnis and Crivello, 2011;Sanderson and van den Berg, 2003;Tabb and Blumberg, 2006). It has been demonstrated that TBT altered the levels of testosterone and oestradiol so that induced a potential masculinization in clams (Morcillo and Porte, 2000). ...
Organotin compounds (OTs) are used in a range of industrial products, such as antifouling paints, agricultural pesticides and stabilizers. Owing to potential endocrine-disrupting effects, human exposure to such compounds is a concern. Nevertheless, little is known about the adverse effect of OTs on adrenocortical function in organisms. In this study, the human adrenocortical carcinoma cell (H295R) model was used to investigate effects of OTs on steroidogenesis and potential causes for such endocrine disruption was examined. H295R cells were exposed to several commonly used OTs, including triphenyltin (TPT), tributyltin (TBT), dibutyltin (DBT), and monobutyltin (MBT), and the production level of steroid hormones were quantified. TPT and TBT decreased the production levels of 17β-estradiol, aldosterone, and cortisol, but increased that of testosterone. Furthermore, the expression levels of ten major steroidogenic genes (HMGR, StAR, CYP11A1, 3βHSD2, CYP17, CYP19A1, CYP21, CYP11B1, CYP11B2, and 17βHSD) were examined and both up-regulation of CYP11B2 and down-regulation of StAR, 3βHSD2, CYP19A1, CYP21 and CYP11B1 by TPT and TBT were observed. Intracellular levels of ATP and cyclic adenosine monophosphate (cAMP) and the activity of adenylate cyclase (AC) decreased in the H295R cells treated with TPT and TBT. No obvious changes in H295R were found with the treatment of DBT and MBT. These results suggest that OTs may stimulate steroidogenesis in vitro via inhibition of cAMP signaling pathway.
