Impact of childhood nephrotic syndrome on obesity and growth: a prospective cohort study.

BACKGROUND: Children with nephrotic syndrome are at risk of obesity and growth impairment from repeated steroid treatment. However, incidence and risk factors for obesity and short stature remain uncertain, which is a barrier to preventative care. Our aim was to determine risk, timing, and predictors of obesity and short stature among children with nephrotic syndrome. METHODS: We evaluated obesity and longitudinal growth among children (1-18 years) enrolled in Insight into Nephrotic Syndrome: Investigating Genes, Health, and Therapeutics. We included children with nephrotic syndrome diagnosed between 1996-2019 from the Greater Toronto Area, Canada, excluding congenital or secondary nephrotic syndrome. Primary outcomes were obesity (body mass index Z-score ≥ + 2) and short stature (height Z-score ≤ -2). We evaluated prevalence of obesity and short stature at enrolment (< 1-year from diagnosis) and incidence during follow-up. Cox proportional hazards models determined the association between nephrotic syndrome classification and new-onset obesity and short stature. RESULTS: We included 531 children with nephrotic syndrome (30% frequently relapsing by 1-year). At enrolment, obesity prevalence was 23.5%, 51.8% were overweight, and 4.9% had short stature. Cumulative incidence of new-onset obesity and short stature over median 4.1-year follow-up was 17.7% and 3.3% respectively. Children with frequently relapsing or steroid dependent nephrotic syndrome within 1-year of diagnosis were at increased risk of new-onset short stature (unadjusted hazard ratio 3.99, 95%CI 1.26-12.62) but not obesity (adjusted hazard ratio 1.56, 95%CI 0.95-2.56). Children with ≥ 7 and ≥ 15 total relapses were more likely to develop obesity and short stature, respectively. CONCLUSIONS: Obesity is common among children with nephrotic syndrome early after diagnosis. Although short stature was uncommon overall, children with frequently relapsing or steroid dependent disease are at increased risk of developing short stature. Effective relapse prevention may reduce steroid toxicity and the risk of developing obesity or short stature.

Thyroid axis participates in high-temperature-induced male sex reversal through its activation by the stress response.

Environmental changes alter the sex fate in about 15% of vertebrate orders, mainly in ectotherms such as fish and reptiles. However, the effects of temperature changes on the endocrine and molecular processes controlling gonadal sex determination are not fully understood. Here, we provide evidence that thyroid hormones (THs) act as co-players in heat-induced masculinization through interactions with the stress axis to promote testicular development. We first demonstrated that the thyroid axis (through thyroid-related genes and T3 levels) is highly active in males during the gonadal development in medaka (Oryzias latipes). Similarly, T3 treatments promoted female-to-male sex reversal in XX embryos. Subsequently, embryonic exposure to temperature-induced stress up-regulated the genes related to the thyroid and stress axes with a final increase in T3 levels. In this context, we show that blocking the stress axis response by the loss of function of the corticotropin-releasing hormone receptors suppresses thyroid-stimulating hormone expression, therefore, heat-induced activation of the thyroid axis. Thus, our data showed that early activation of the stress axis and, in consequence, the TH axis, too, leaves us with that both being important endocrine players in inducing female-to-male reversal, which can help predict possible upcoming physiological impacts of global warming on fish populations.

Investigating the anti-bioadhesion properties of short, medium chain length, and amphiphilic polyhydroxyalkanoate films.

Silicone materials are widely used in fouling release coatings, but developing eco-friendly protection via biosourced coatings, such as polyhydroxyalcanoates (PHA) presents a major challenge. Anti-bioadhesion properties of medium chain length PHA and short chain length PHA films are studied and compared with a reference Polydimethylsiloxane coating. The results highlight the best capability of the soft and low-roughness PHA-mcl films to resist bacteria or diatoms adsorption as compared to neat PDMS and PHBHV coatings. These parameters are insufficient to explain all the results and other properties related to PHA crystallinity are discussed. Moreover, the addition of a low amount of PEG copolymers within the coatings, to create amphiphilic coatings, boosts their anti-adhesive properties. This work reveals the importance of the physical or chemical ambiguity of surfaces in their anti-adhesive effectiveness and highlights the potential of PHA-mcl film to resist the primary adhesion of microorganisms.

Hydrogel Based on Polyhydroxyalkanoate Sulfonate: Control of the Swelling Rate by the Ionic Group Content.

Hydrogels based on poly(3-hydroxyalkanoate) (PHA) sulfonate and poly(ethylene glycol) diacrylate, PEGDA, are prepared. First, PHA sulfonate is synthesized from unsaturated PHA by a thiol-ene reaction in the presence of sodium-3-mercapto-1-ethanesulfonate. The hydrophilicity of PHAs is considerably increased by adding sulfonate functions, and three amphiphilic PHAs are synthesized, containing 10, 22, or 29% sulfonate functions. Then, hydrogels are formed in the presence of PEGDA having different molar masses, that is, 575 or 2000 g mol-1. The hydrogels show fibrillar and porous structures observed in cryo-MEB with pore sizes that vary according to the content of sulfonated groups (10 to 29 mol %) ranging from 50 to more than 150 nm. Furthermore, depending on the proportions of the two polymers, a variable rigidity is observed from 2 to 40 Pa. In fact, the evaluation of the dynamic mechanical properties of the hydrogel determined by DMA reveals that the less rigid hydrogels hinder the adhesion of Pseudomonas aeruginosa PaO1 bacteria. Finally, these hydrogels swelling up to 5000% are noncytotoxic, allowing the adhesion and amplification of immortalized C2C12 cells, and they are therefore seen as promising materials both for repelling PaO1 bacteria and for amplifying myogenic cells.

Early developmental toxicity of Atlantic salmon exposed to conventional and unconventional oils.

Atlantic salmon is an important species for Canadian culture and economy and its importance extends beyond Canada to Scandinavia and Western Europe. However, it is a vulnerable species facing decline due to habitat contamination and destruction. Existing and new Canadian pipeline projects pose a threat to salmonid habitat. The effects of diluted bitumen (dilbit), the main oil circulating in pipelines, are less studied than those of conventional oils, especially during the critical early embryonic developmental stage occurring in freshwater ecosystems. Therefore, this study aimed to compare the effects of water-accommodated fractions (WAF) of the Clearwater McMurray dilbit and the Lloydminster Heavy conventional oil on Atlantic salmon embryos exposed either from fertilization or from eyed stage. The dilbit contained the highest concentrations of low molecular weight (LMW) compounds (including BTEX and C6-C10), while the conventional oil contained the highest concentrations of PAHs. The Clearwater dilbit caused a higher percentage of mortality and malformations than the conventional oil at similar WAF concentrations. In addition, the embryos exposed from fertilization suffered a higher mortality rate, more developmental delays, and malformations than embryos exposed from the eyed stage, suggesting that early development is the most sensitive developmental stage to oil exposure. Gene expression and enzymatic activity of the detoxification phase I and II enzymes (CYP1A and GST) were measured. Data showed increases in both cyp1a expression and GST activity with increasing WAF concentrations, while gst expression was not affected by the exposures. Also, gene expression of proteins involved in the biotransformation of vitamin A and DNA damage repair were modified by the oil exposures. Overall, this study indicates that Atlantic salmon is mostly affected by oil exposure at the beginning of its development, during which embryos accumulate deformities that may impact their survival at later life stages.

The central nervous system acts as a transducer of stress-induced masculinization through corticotropin-releasing hormone B.

Exposure to environmental stressors, such as high temperature (HT), during early development of fish induces sex reversal of genotypic females. Nevertheless, the involvement of the brain in this process is not well clarified. In the present work, we investigated the mRNA levels of corticotropin-releasing hormone b (crhb) and its receptors (crhr1 and crhr2), and found that they were upregulated at HT during the crucial period of gonadal sex determination in medaka. In order to clarify their roles in sex reversal, biallelic mutants for crhr1 and crhr2 were produced by CRISPR/Cas9 technology. Remarkably, biallelic mutants of both loci (crhr1 and crhr2) did not undergo female-to-male sex reversal upon exposure to HT. Inhibition of this process in double corticotropin-releasing hormone receptor mutants could be successfully rescued through the administration of the downstream effector of the hypothalamic-pituitary-interrenal axis, cortisol. Taken together, these results reveal for the first time that the CNS acts as a transducer of masculinization induced by thermal stress.

Disruption by stealth - Interference of endocrine disrupting chemicals on hormonal crosstalk with thyroid axis function in humans and other animals.

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.

Towards regulation of Endocrine Disrupting chemicals (EDCs) in water resources using bioassays - A guide to developing a testing strategy.

Endocrine disrupting chemicals (EDCs) are found in every environmental medium and are chemically diverse. Their presence in water resources can negatively impact the health of both human and wildlife. Currently, there are no mandatory screening mandates or regulations for EDC levels in complex water samples globally. Bioassays, which allow quantifying in vivo or in vitro biological effects of chemicals are used commonly to assess acute toxicity in water. The existing OECD framework to identify single-compound EDCs offers a set of bioassays that are validated for the Estrogen-, Androgen-, and Thyroid hormones, and for Steroidogenesis pathways (EATS). In this review, we discussed bioassays that could be potentially used to screen EDCs in water resources, including in vivo and in vitro bioassays using invertebrates, fish, amphibians, and/or mammalians species. Strengths and weaknesses of samples preparation for complex water samples are discussed. We also review how to calculate the Effect-Based Trigger values, which could serve as thresholds to determine if a given water sample poses a risk based on existing quality standards. This work aims to assist governments and regulatory agencies in developing a testing strategy towards regulation of EDCs in water resources worldwide. The main recommendations include 1) opting for internationally validated cell reporter in vitro bioassays to reduce animal use & cost; 2) testing for cell viability (a critical parameter) when using in vitro bioassays; and 3) evaluating the recovery of the water sample preparation method selected. This review also highlights future research avenues for the EDC screening revolution (e.g., 3D tissue culture, transgenic animals, OMICs, and Adverse Outcome Pathways (AOPs)).

A comprehensive review on current technologies for removal of endocrine disrupting chemicals from wastewaters.

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.

Validity and utility of urinary CXCL10/Cr immune monitoring in pediatric kidney transplant recipients.

Individualized posttransplant immunosuppression is hampered by suboptimal monitoring strategies. To validate the utility of urinary CXCL10/Cr immune monitoring in children, we conducted a multicenter prospective observational study in children <21 years with serial and biopsy-associated urine samples (n = 97). Biopsies (n = 240) were categorized as normal (NOR), rejection (>i1t1; REJ), indeterminate (IND), BKV infection, and leukocyturia (LEU). An independent pediatric cohort of 180 urines was used for external validation. Ninety-seven patients aged 11.4 ± 5.5 years showed elevated urinary CXCL10/Cr in REJ (3.1, IQR 1.1, 16.4; P < .001) and BKV nephropathy (median = 5.6, IQR 1.3, 26.9; P < .001) vs. NOR (0.8, IQR 0.4, 1.5). The AUC for REJ vs. NOR was 0.76 (95% CI 0.66-0.86). Low (0.63) and high (4.08) CXCL10/Cr levels defined high sensitivity and specificity thresholds, respectively; validated against an independent sample set (AUC = 0.76, 95% CI 0.66-0.86). Serial urines anticipated REJ up to 4 weeks prior to biopsy and declined within 1 month following treatment. Elevated mean CXCL10/Cr was correlated with first-year eGFR decline (ρ = -0.37, P ≤ .001), particularly when persistently exceeding ≥4.08 (ratio = 0.81; P < .04). Useful thresholds for urinary CXCL10/Cr levels reproducibly define the risk of rejection, immune quiescence, and decline in allograft function for use in real-time clinical monitoring in children.

Synthesis of Fluorinated Polyhydroxyalkanoates from Marine Bioresources as a Promising Biomaterial Coating.

By successive enzymatic and chemical modifications, novel fluorinated polyhydroxyalkanoates were synthesized and characterized. Unsaturated polyhydroxyalkanoate, PHAU, was first produced by fermentation using marine bacteria Pseudomonas raguenesii, and a graft copolymer PHAU-g-C8F17 was further prepared by controlled thiol-ene reaction in the presence of perfluorodecanethiol (PFDT). The PFDT grafting is realized by two different processes. In the first method, PHAU was previously solubilized in toluene. The grafting in solution is more efficient than the direct heterogeneous grafting onto a PHAU film. The degrees of grafting were determined by 1H NMR. The characterization of the microstructure by SEM-EDX and modulated and conventional DSC showed the formation of microdomains due to the organization of the hydrophobic segments of graft PFDT. Biomaterials prepared by 3D printing and coated by PHAU-g-C8F17 have the potential to be used as novel contrast agents as shown by Hahn echo experiments.

Blending Ferulic Acid Derivatives and Polylactic Acid into Biobased and Transparent Elastomeric Materials with Shape Memory Properties.

Thanks to its remarkable properties such as sustainability, compostability, biocompatibility, and transparency, poly-l-lactic acid (PLA) would be a suitable replacement for oil-based polymers should it not suffer from low flexibility and poor toughness, restricting its use to rigid plastic by excluding elastomeric applications. Indeed, there are few fully biobased and biodegradable transparent elastomers-PLA-based or not-currently available. In the last decades, many strategies have been investigated to soften PLA and enhance its toughness and elongation at break by using plasticizers, oligomers, or polymers. This work shows how a ferulic acid-derived biobased additive (BDF) blends with a common rigid and brittle commercial grade of polylactic acid to provide a transparent non-covalently cross-linked elastomeric material with shape memory behavior exhibiting an elongation at break of 434% (vs 6% for pristine PLA). Through a structure-activity relationship analysis conducted with BDF analogues and a modeling study, we propose a mechanism based on π-π stacking to account for the elastomeric properties. Blending ferulic acid derivatives with polylactic acid generates a new family of fully sustainable transparent elastomeric materials with functional properties such as shape memory.

Frogs Respond to Commercial Formulations of the Biopesticide Bacillus thuringiensis var. israelensis, Especially Their Intestine Microbiota.

It is generally believed that Bacillus thuringiensis var. israelensis (Bti) biopesticides are harmless to non-target organisms; however, new research shows controversial results. We exposed acutely and chronicallyLithobates sylvaticusandAnaxyrus americanus tadpoles until metamorphic climax to VectoBac 200G (granules) and VectoBac 1200L (aqueous suspension) at 300-20,000 ITU/L covering field-relevant concentrations and higher. The data show that the exposure parameters tested did not affect significantly the survival, total length, total weight, hepatosomatic index, gonadosomatic index, the expression of genes of interest (i.e., related to xenobiotic exposure, oxidative stress, and metamorphosis), and the intestine tissue layer detachment ofL. sylvaticusandA. americanus in a concentration-response pattern. In contrast, VectoBac 200G significantly increased the median time to metamorphosis ofL. sylvaticus tadpoles by up to 3.5 days and decreased the median by up to 1 day inA. americanus. VectoBac 1200L significantly increased the median time to metamorphosis ofL. sylvaticusandA. americanustadpoles by up to 4.5 days. Also, the exposure to VectoBac 200G and 1200L altered the intestine bacterial community composition inA. americanus at application rates recommended by the manufacturer, which led to an increase in the relative abundance of Verrucomicrobia, Firmicutes, Bacteroidetes, and Actinobacteria. Changes in the intestine microbiota might impact the fitness of individuals, including the susceptibility to parasitic infections. Our results indicate that the effect of Bti commercial products is limited; however, we recommend that Bti-spraying activities in amphibian-rich ecosystems should be kept minimal until there is more conclusive research to assess if the changes in the time to metamorphosis and microbiota can lead to negative outcomes in amphibian populations and, eventually, the functioning of ecosystems.

Impact of steroids and steroid-sparing agents on quality of life in children with nephrotic syndrome.

BACKGROUND: Steroids and/or steroid-sparing medications are commonly used for nephrotic syndrome treatment; however, the impact of these medications on health-related quality of life over time is not well described. METHODS: Longitudinal cohort is up to 5 years where children were assessed with baseline and annual Pediatric Quality of Life Inventory questionnaire. A mixed-effects linear regression determined differences in scores among children receiving steroids and/or steroid-sparing agents for at least 30 days compared with those not on medication at 1, 3, 6, and 12 months prior to assessment. RESULTS: Among 295 children, 64% were male, with a median age of 3.7 (interquartile range [IQR], 2.7, 5.9) years at diagnosis, and comprised 25% Europeans, 40% South Asians, and 8% East/Southeast Asians. Adjusted HRQOL scores were reduced among children taking steroids and steroid-sparing agents among 705 HRQOL measures (median 2 [IQR, 1, 3] per child). Compared to children without medication, steroid and steroid-sparing agent use up to 12 months prior to assessment were associated with an overall HRQOL drop of 3.17 (95% confidence interval [CI], - 5.25, - 1.08) and 3.18 (95% CI, - 5.24, - 1.12), respectively, after adjustment. Functioning domain scores were reduced by 4.41 points (95% CI, - 6.57, - 2.25) in children on steroids, whereas fatigue domain scores were reduced by 5.47 points (95% CI, - 9.28, - 1.67) in children on steroid-sparing agents after adjustment. CONCLUSIONS: HRQOL is consistently decreased in children receiving steroids and steroid-sparing agents, with differential effects on functioning and fatigue. Counseling families on possible effects of prolonged treatment periods is important in the management of childhood nephrotic syndrome.

Chronic Exposure to Two Gestagens Differentially Alters Morphology and Gene Expression in Silurana tropicalis.

Gestagens are active ingredients in human and veterinary drugs with progestogenic activity. Two gestagens-progesterone (P4), and the synthetic P4 analogue, melengestrol acetate (MGA)-are approved for use in beef cattle agriculture in North America. Both P4 and MGA have been measured in surface water receiving runoff from animal agricultural operations. This project aimed to assess the morphometric and molecular consequences of chronic exposures to P4, MGA, and their mixture during Western clawed frog metamorphosis. Chronic exposure (from embryo to metamorphosis) to MGA (1.7 µg/L) or P4 + MGA (0.22 µg/L P4 + 1.5 µg/L MGA) caused a considerable dysregulation of metamorphic timing, as evidenced by an inhibition of growth, narrower head, and lack of forelimb emergence in all animals. Molecular analysis revealed that chronic exposure to the mixture induced an additive upregulation of neurosteroid-related (GABAA receptor subunit α6 (gabra6) and steroid 5-alpha reductase 1 (srd5α1) gene expression in brain tissue. Chronic P4 exposure (0.26 µg/L P4) induced a significant upregulation of the expression hypothalamic-pituitary-gonadal (HPG)-related genes (ipgr, erα) in the gonadal mesonephros complex (GMC). Our data suggest that exposure to P4, MGA, and their mixture induces multiple endocrine responses and adverse effects in larval Western clawed frogs. This study helps to better our understanding of the consequences of chronic gestagen exposure and suggests that the implications and risk of high gestagen use in beef cattle feeding operations may extend to the aquatic environment.

A Review of the Effects of the Biopesticides Bacillus thuringiensis Serotypes israelensis (Bti) and kurstaki (Btk) in Amphibians.

Insecticides are important in agriculture, to reduce human disease, and to decrease the nuisance of biting insects. Despite this, many have the potential for environmental impacts and toxicity in nontarget organisms. We reviewed data on the effects of insecticides based on toxins from Bacillus thuringiensis var. israelensis (Bti) and Bacillus thuringiensis var. kurstaki (Btk) on amphibians. The few peer-reviewed publications that are available for Bti provide variable conclusions, ranging from few observable effects to evidence of acute toxicity at high concentrations. We briefly highlight the current controversies and identify key areas for future investigation.

Burden of cytomegalovirus DNAemia among pediatric renal transplant patients on antiviral prophylaxis: A hospital-based analysis.

INTRODUCTION: We examined the burden of CMV DNAemia and time to such events among renal transplant patients receiving CMV prophylaxis. We targeted the first year after transplantation, with the primary focus being on the first 3 months. METHODS: We conducted a retrospective review of renal transplant patients (<18 years) who were transplanted and followed at our center between January 2007, and December 2017. Clinical and laboratory data were obtained from the medical records and laboratory databases. RESULTS: Among 141 patients, the median age at transplant was 12.7 years (range 0.87-17.83 years). CMV DNAemia was detected in 33 of 77 patients eligible for prophylaxis (42.9%; 95% CI 31.6-54.6) during the first post-transplant year. Proportionately more D+R- patients were present among patients with DNAemia compared with those without DNAemia (15/38, 39.5% vs 16/103, 15.5%, P = .005). Median time to first positivity was 134 days (range 0-304 days). Eight patients had a positive PCR during the first 3 months (5.7% of all patients). Among those eligible for prophylaxis, 6.5% had DNAemia during the first 3 months while on prophylaxis. Among patients whose first positive PCR was after 3 months post-transplant, the median time to positivity was 52 days (range 13-214 days) after the end of prophylaxis. CONCLUSIONS: Breakthrough CMV DNAemia was documented among children receiving antiviral prophylaxis. While routine monitoring while on prophylaxis might not be warranted for the majority of patients, studies are needed to determine the optimal indications for CMV PCR testing while on prophylaxis.

Consequences of steroid-5α-reductase deficiency and inhibition in 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,17ß-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.

High temperature stress response is not sexually dimorphic at the whole-body level and is dependent on androgens to induce sex reversal.

The understanding of the molecular and endocrine mechanisms behind environmentally-induced sex reversal in fish is of great importance in the context of predicting the potential effects of climate change, especially increasing temperature. Here, we demonstrate the global effects of high temperature on genome-wide transcription in medaka (Oryzias latipes) during early development. Interestingly, data analysis did not show sexual dimorphic changes, demonstrating that thermal stress is not dependent on genotypic sex. Additionally, our results revealed significant changes in several pathways under high temperature, such as stress response from brain, steroid biosynthesis, epigenetic mechanisms, and thyroid hormone biosynthesis, among others. These microarray data raised the question of what the exact molecular and hormonal mechanisms of action are for female-to-male sex reversal under high temperatures in fish. Complementary gene expression analysis revealed that androgen-related genes increase in females (XX) experiencing high water temperature. To test the involvement of androgens in thermal-induced sex reversal, an androgen antagonist was used to treat XX medaka under a high-temperature setup. Data clearly demonstrated failure of female-to-male sex reversal when androgen action is inhibited, corroborating the importance of androgens in environmentally-induced sex reversal.

Multi-Level Responses of Yellow Perch (Perca flavescens) to a Whole-Lake Nanosilver Addition Study.

Silver nanoparticles (AgNP) are widely used as antibacterial agents in both commercial products and for industrial applications. As such, AgNP has a high potential for release into freshwater environments. As part of a whole-lake ecosystem experiment to examine the impacts of AgNP exposure at low µg/L concentrations over multiple years, we evaluated biological responses in Yellow Perch (Perca flavescens) before, during, and after AgNP additions to a freshwater lake. Yellow Perch were monitored for responses to in situ AgNP additions at the cellular (suite of biomarkers), individual (growth, prey consumption, and metabolism), and population (abundance and gross prey consumption) scales. At the cellular level, several biomarkers of oxidative stress in liver tissues revealed down-regulation, including decreased mRNA levels of catalase and glutathione peroxidase in Yellow Perch collected during AgNP exposure, and elevated ratios of reduced to oxidized glutathione. At the individual level, Yellow Perch bioenergetic models revealed that prey consumption and total metabolism significantly declined during AgNP additions and remained depressed one year after AgNP addition. At the population level, Yellow Perch densities and gross prey consumption declined after AgNP was added to the lake. Together, these results reveal a holistic assessment of the negative impacts of chronic exposure to environmentally relevant AgNP concentrations (i.e., µg/L) on Yellow Perch at cellular, individual, and population levels.