•SRD5αs synthesize androgen (5α-dihydrotestosterone) and neurosteroid (allopregnanolone).•SRD5αs are also involved in N-glycosylation and steroid degradation.•SRD5αs are regulated by several hormones ...and DNA methylation.•SRD5α inhibition leads to similar physiological deficiencies across vertebrates.
In 1974, a lack of 5α-dihydrotestosterone (5α-DHT), the most potent androgen across species except for fish, was shown to be the origin of a type of pseudohermaphrodism in which boys have female-like external genitalia. This human intersex condition is linked to a mutation in the steroid-5α-reductase type 2 (SRD5α2) gene, which usually produces an important enzyme capable of reducing the Δ4-ene of steroid C-19 and C-21 into a 5α-stereoisomer. Seeing the potential of SRD5α2 as a target for androgen synthesis, pharmaceutical companies developed 5α-reductase inhibitors (5ARIs), such as finasteride (FIN) and dutasteride (DUT) to target SRD5α2 in benign prostatic hyperplasia and androgenic alopecia. In addition to human treatment, the development of 5ARIs also enabled further research of SRD5α functions. Therefore, this review details the morphological, physiological, and molecular effects of the lack of SRD5α activity induced by both SRD5α mutations and inhibitor exposures across species. More specifically, data highlights 1) the role of 5α-DHT in the development of male secondary sexual organs in vertebrates and sex determination in non-mammalian vertebrates, 2) the role of SRD5α1 in the synthesis of the neurosteroid allopregnanolone (ALLO) and 5α-androstane-3α,17β-diol (3α-diol), which are involved in anxiety and sexual behavior, respectively, and 3) the role of SRD5α3 in N-glycosylation. This review also features the lesser known functions of SRD5αs in steroid degradation in the uterus during pregnancy and glucocorticoid clearance in the liver. Additionally, the review describes the regulation of SRD5αs by the receptors of androgens, progesterone, estrogen, and thyroid hormones, as well as their differential DNA methylation. Factors known to be involved in their differential methylation are age, inflammation, and mental stimulation. Overall, this review helps shed light on the various essential functions of SRD5αs across species.
Highlights • Plasticizers disrupt animal development via the thyroid hormone axis. • Plasticizers impede with reproduction by reducing mitochondrial cholesterol transport. • Plasticizers also induce ...cellular stress by increasing fatty acid oxidation.
Despite the urge need to address the possible impact of plastic debris, up to now, little is known about the translocation of nanoplastics through the trophic web. Plus, due to their surface ...reactivity, nanoplastics could sorb and thus increase metals bioavailability to aquatic filter-feeding organisms (e.g., bivalves). In this study, we investigated the dietary exposure route on the oyster Crassostrea virginica through microalgae themselves exposed to three nanoplastic dispersions (PSL, PSC and NPG) at reportedly environmental concentrations combined or not with arsenic. Interactive effects of nanoplastics on arsenic bioaccumulation were studied, along with the expression of key genes in gills and visceral mass. The investigated gene functions were endocytosis (cltc), oxidative stress (gapdh, sod3, cat), mitochondrial metabolism (12S), cell cycle regulation (gadd45, p53), apoptosis (bax, bcl-2), detoxification (cyp1a, mdr, mt), and energy storage (vit). Results showcased that nanoplastic treatments combined with arsenic triggered synergetic effects on gene expressions. Relative mRNA level of 12S significantly increased at 10 and 100 μg L−1 for NPG combined with arsenic and for PSC combined with arsenic. Relative mRNA level of bax increased for PSL combined with arsenic and for PSC combined with arsenic at 10 and 100 μg L−1 respectively. We also observed that relative arsenic bioaccumulation was significantly higher in Crassostrea virginica gills compared to Isognomon alatus’. These results are the first comparative molecular effects of nanoplastics alone and combined with arsenic investigated in farmed C. virginica oysters. Together with I. alatus results we thus shed light on species different sensitivity.
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•Nanoplastics are adsorbed on microalgae surface starting at 10 μg L−1 exposure.•Nanoplastics triggered apoptotic and mitochondrial metabolism gene responses.•The combination of nanoplastics with arsenic induced synergetic effects.•Arsenic bioaccumulation did not increase in the presence of nanoplastics.
•Rainbow trout larvae were exposed to WAFs from two conventional oils and two dilbits.•Increase of EROD activity and DNA damage were observed for all oils.•Increase of skeletal malformations and ...haemorrhages were observed for most oils.•Spectra and intensity of effects depend on chemical composition of oils.
Petroleum hydrocarbons are widely used and transported, increasing the risks of spills to the environment. Although conventional oils are the most commonly produced, the production of unconventional oils (i.e. diluted bitumen or dilbit) is increasing. In this study, we compared the effects of conventional oils (Arabian Light and Lloydminster) and dilbits (Bluesky and Clearwater) on early life stages of a salmonid. To this end, aqueous fractions (WAF: water accommodated fraction) of these oils were extracted using mountain spring water. Rainbow trout (Oncorhynchus mykiss) larvae were exposed to 10 and 50% dilutions of these WAFs from hatching (340 DD; degree days) until yolk sac resorption (541 DD). Exposure to WAFs increased skeletal malformations (both dilbits) and hemorrhage (both conventional oils and Bluesky) and decreased head growth (Arabian Light). In addition, increases in EROD activity and DNA damage were measured for all oils and an increase in cyp1a gene expression was measured for Arabian Light, Bluesky and Clearwater. The PAH and C10C50 concentrations were positively correlated to total larval EROD activity, whereas concentrations of total hydrocarbons, VOCs, PAHs, and C10C50 were positively correlated to cyp1a expression. Total hydrocarbon, VOC, and C10C50 concentrations were also negatively correlated to larval growth. This study supports that petroleum hydrocarbons are toxic to early developmental stages of rainbow trout and show that their degree and spectrum of toxicity depends on their chemical composition.
Comprehenders have been shown to use both syntactic and semantic cues to understand pronouns like he and she. In Ana threw the ball to Liz. She…, there is a syntactic bias to assign “she” to the ...previous subject (Ana), and a semantic bias to assign it to the goal referent (Liz). How do people learn these biases? We tested how sensitivity to these cues is modulated by linguistic experience, measured with an Author Recognition Task (Stanovich & West, 1989). In two experiments, we found both the subject and goal biases overall, but higher print exposure only predicted use of the subject bias, not the goal bias. Our results suggest that the subject bias, and not the goal bias, may be learned from exposure.
In the recent years, endocrine disrupting compounds (EDCs) has received increasing attention due to their significant toxic effects on human beings and wildlife by affecting their endocrine systems. ...As an important group of emerging pollutant, EDCs have been detected in various aquatic environments, including surface waters, groundwater, wastewater, runoff, and landfill leachates. Their removal from water resources has also been an emerging concern considering growing population as well as reducing access to fresh water resources. EDC removal from wastewaters is highly dependent on physicochemical properties of the given EDCs present in each wastewater types as well as various aquatic environments. Due to chemical, physical and physicochemical diversities in these parameters, variety of technologies consisting of physical, biological, electrochemical, and chemical processes have been developed for their removal. This review highlights that the effectiveness of EDC removal is highly dependent of selecting the appropriate technology; which decision is made upon a full wastewater chemical characterization. This review aims to provide a comprehensive perspective about all the current technologies used for EDCs removal from various aquatic matrices along with rising challenges such as the antimicrobial resistance gene transfer during EDC treatment.
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•EDC removal methods include physical, chemical, electrochemical, and/or biological treatments.•Effectiveness of EDC removal is highly dependent of selecting the appropriate technology.•Full wastewater chemical characterization is key prior selecting the removal method to be used.
Diluted bitumen (dilbit) from Alberta oil sands (Canada) is transported across major continental watersheds, yet little is known about its toxicity to fish if spilled into aquatic environments. The ...toxicity of Cold Lake (CLB) dilbit was assessed for medaka embryos (Oryzias latipes) exposed to water accommodated fractions (WAF) and chemically-enhanced WAF (CEWAF) using Corexit®EC9500A as dispersant. The effects of CLB toxicity were similar to conventional crude oils and Access Western Blend (AWB) dilbit. The prevalence of malformations and cyp1a mRNA synthesis in hatched fish increased monotonically with concentration during WAF and CEWAF treatments and provided a novel indicator of dilbit PAH toxicity. Apart from nfe2 (an antioxidant transcription factor), there were no statistically significant monotonic exposure-responses of ahr, arnt2, cat, sod, gpx, gst, gsr, g6pdh, p53, and hsp70 transcripts at total polycyclic aromatic hydrocarbons (TPAH) concentrations bracketing EC50s for embryotoxicity (WAF ≅ 3 μg/L; CEWAF ≅ 0.1 μg/L TPAH). Based on measured TPAH concentrations in exposure test solutions, CLB dilbit was 6–10 fold more toxic to medaka than AWB during chronic exposures. Lack of direct monotonic gene transcription responses to increasing oil concentrations during exposures that were embryotoxic suggests that the capacity of the oxidative stress response is limited in earlier lifestages or that differences exist among species in mechanisms of toxicity. This study provides a comparative framework for identifying suitable biomarkers and toxicity methods for those fish species in sensitive lifestages at highest risk of Canadian oil sands dilbit exposure following a spill in the freshwater environment.
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•Novel embryotoxicity data of Cold Lake Blend (CLB) diluted bitumen (dilbit).•Original comparison of toxicity of Canada's two predominant oil sands dilbit blends.•Unique description of predictive dilbit toxicity via cyp1a transcripts.•Framework for the assessment of embryotoxicity by non-conventional oil mixtures.
This study was performed to assess the toxicity of Cold Lake Blend (CLB) diluted bitumen (dilbit) from Canada's oil sands region to embryonic freshwater fish.
Canada has experienced a significant increase in the transport of diluted bitumen (dilbit), a predominant oil sands product that combines bitumen with diluents derived from oil–gas condensates and ...other proprietary compounds. The proportion of diluent and the chemical composition of dilbit vary to meet seasonal transport requirements. While the toxic effects of a variety of crude and refined oils are well-studied, the toxicity of dilbit to aquatic species is less well known. This focused review summarizes dilbit production, chemistry, and the few data on toxicity to aquatic species. These data suggest that un-weathered dilbit would cause effects on fish equivalent to those of conventional oils, but its toxicity may be lower, depending on interactions among test conditions, the behavior of dilbit added to water and the species tested.
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•P4-receptors are expressed in early larval development in S. tropicalis.•P4 upregulated gene expression of ipgr, mpgrβ, pgrmc1, ar, and srd5α1, 2, and 3.•MGA exposure induced a ...dissimilar molecular response to P4.•MGA exposure inhibited transcription of srd5α3 in a concentration-dependent manner.
Environmental gestagens are an emerging class of contaminants that have been recently measured in surface water and can interfere with reproduction in aquatic vertebrates. Gestagens include endogenous progestogens, such as progesterone (P4), which bind P4-receptors and have critically important roles in vertebrate physiology and reproduction. Gestagens also include synthetic progestins, which are components of human and veterinary drugs, such as melengestrol acetate (MGA). Endogenous progestogens are essential in the regulation of reproduction in mammalian species, but the role of P4 in amphibian larval development remains unclear. This project aims to understand the roles and the regulatory mechanisms of P4 in amphibians and to assess the consequences of exposures to environmental gestagens on the P4-receptor signaling pathways in frogs. Here, we established the developmental profiles of the P4 receptors: the intracellular progesterone receptor (ipgr), the membrane progesterone receptor β (mpgrβ), and the progesterone receptor membrane component 1 (pgrmc1) in Western clawed frog (Silurana tropicalis) embryos using real-time qPCR. P4-receptor mRNAs were detected throughout embryogenesis. Transcripts for ipgr and pgrmc1 were detected in embryos at Nieuwkoop and Faber (NF) stage 2 and 7, indicative of maternal transfer of mRNA. We also assessed the effects of P4 and MGA exposure in embryonic and early larval development. Endocrine responses were evaluated through transcript analysis of a suite of gene targets of interest, including: ipgr, mpgrβ, pgrmc1, androgen receptor (ar), estrogen receptor α (erα), follicle stimulating hormone β (fshβ), prolactin (prl), and the steroid 5-alpha reductase family (srd5α1, 2, and 3). Acute exposure (NF 12–46) to P4 caused a 2- to 5-fold change increase of ipgr, mpgrβ, pgrmc1, and ar mRNA levels at the environmentally relevant concentration of 195 ng/L P4. Acute exposure to MGA induced a 56% decrease of srd5α3 at 1140 ng/L MGA. We conclude that environmental exposure to P4 induced multiple endocrine-related transcript responses in amphibians; however, the differential responses of MGA suggest that the effects of MGA are not mediated through the classical P4 signaling pathway in S. tropicalis.
Thyroid hormones (THs) are important regulators of growth, development, and homeostasis of all vertebrates. There are many environmental contaminants that are known to disrupt TH action, yet their ...mechanisms are only partially understood. While the effects of Endocrine Disrupting Chemicals (EDCs) are mostly studied as “hormone system silos”, the present critical review highlights the complexity of EDCs interfering with TH function through their interactions with other hormonal axes involved in reproduction, stress, and energy metabolism. The impact of EDCs on components that are shared between hormone signaling pathways or intersect between pathways can thus extend beyond the molecular ramifications to cellular, physiological, behavioral, and whole-body consequences for exposed organisms. The comparatively more extensive studies conducted in mammalian models provides encouraging support for expanded investigation and highlight the paucity of data generated in other non-mammalian vertebrate classes. As greater genomics-based resources become available across vertebrate classes, better identification and delineation of EDC effects, modes of action, and identification of effective biomarkers suitable for HPT disruption is possible. EDC-derived effects are likely to cascade into a plurality of physiological effects far more complex than the few variables tested within any research studies. The field should move towards understanding a system of hormonal systems’ interactions rather than maintaining hormone system silos.
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•Thyroid hormones are important cellular process regulators in vertebrates.•Endocrine disruptors (EDCs) affect the hypothalamus-pituitary-thyroid (HPT) axis.•Reproductive, stress, dietary, and metabolic axes crosstalk with the HPT axis.•This crosstalk presents an additional mode of HPT axis disruption by EDCs.•The present review addresses new research questions to identify vulnerable species.