Publications by authors named "Alper James G Alcaraz"

3 Publications

  • Page 1 of 1

The brominated flame retardant, TBCO, impairs oocyte maturation in zebrafish (Danio rerio).

Aquat Toxicol 2021 Aug 3;238:105929. Epub 2021 Aug 3.

Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, T1K 3M4, Canada; Intersectoral Centre for Endocrine Disruptor Analysis (ICEDA), Institut National de la Recherche Scientifique (INRS), Centre Eau Terre Environnement, Québec City, QC, G1K 9A9, Canada; Water Institute for Sustainable Environments, University of Lethbridge, Lethbridge, AB, T1K 3M4, Canada. Electronic address:

The brominated flame retardant, 1,2,5,6-tetrabromocyclooctane (TBCO), has been shown to decrease fecundity in Japanese medaka (Oryzias latipes) and there is indirect evidence from analysis of the transcriptome and proteome that this effect might be due to impaired oogenesis. An assay for disruption of oocyte maturation by chemical stressors has not been developed in Japanese medaka. Thus, using zebrafish (Danio rerio) as a model, objectives of the present study were to determine whether exposure to TBCO has effects on maturation of oocytes and to investigate potential mechanisms. Sexually mature female zebrafish were given a diet of 35.3 or 628.8 μg TBCO / g food for 14 days after which, stage IV oocytes were isolated to assess maturation in response to maturation inducing hormone. To explore potential molecular mechanisms, abundances of mRNAs of a suite of genes that regulate oocyte maturation were quantified by use of quantitative real-time PCR, and abundances of microRNAs were determined by use of miRNAseq. Ex vivo maturation of oocytes from fish exposed to TBCO was significantly less than maturation of oocytes from control fish. The percentage of oocytes which matured from control fish and those exposed to low and high TBCO were 89, 71, and 67%, respectively. Among the suite of genes known to regulate oocyte maturation, mRNA abundance of insulin like growth factor-3 was decreased by 1.64- and 3.44-fold in stage IV oocytes from females given the low and high concentrations of TBCO, respectively, compared to the control group. Abundances of microRNAs regulating the expression of proteins that regulate oocyte maturation, including processes related to insulin-like growth factor, were significantly different in stage IV oocytes from fish exposed to TBCO. Overall, results of this study indicated that impaired oocyte maturation might be a mechanism of reduced reproductive performance in TBCO-exposed fish. Results also suggested that effects of TBCO on oocyte maturation might be due to molecular perturbations on insulin-like growth factor signaling and expression of microRNAs.
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http://dx.doi.org/10.1016/j.aquatox.2021.105929DOI Listing
August 2021

Assessing the Toxicity of 17α-Ethinylestradiol in Rainbow Trout Using a 4-Day Transcriptomics Benchmark Dose (BMD) Embryo Assay.

Environ Sci Technol 2021 08 22;55(15):10608-10618. Epub 2021 Jul 22.

Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5B3.

There is an urgent demand for more efficient and ethical approaches in ecological risk assessment. Using 17α-ethinylestradiol (EE2) as a model compound, this study established an embryo benchmark dose (BMD) assay for rainbow trout (RBT; ) to derive transcriptomic points-of-departure (tPODs) as an alternative to live-animal tests. Embryos were exposed to graded concentrations of EE2 (measured: 0, 1.13, 1.57, 6.22, 16.3, 55.1, and 169 ng/L) from hatch to 4 and up to 60 days post-hatch (dph) to assess molecular and apical responses, respectively. Whole proteome analyses of alevins did not show clear estrogenic effects. In contrast, transcriptomics revealed responses that were in agreement with apical effects, including excessive accumulation of intravascular and hepatic proteinaceous fluid and significant increases in mortality at 55.1 and 169 ng/L EE2 at later time points. Transcriptomic BMD analysis estimated the median of the 20th lowest geneBMD to be 0.18 ng/L, the most sensitive tPOD. Other estimates (0.78, 3.64, and 1.63 ng/L for the 10th percentile geneBMD, first peak geneBMD distribution, and median geneBMD of the most sensitive over-represented pathway, respectively) were within the same order of magnitude as empirically derived apical PODs for EE2 in the literature. This 4-day alternative RBT embryonic assay was effective in deriving tPODs that are protective of chronic effects of EE2.
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http://dx.doi.org/10.1021/acs.est.1c02401DOI Listing
August 2021

Development of a Comprehensive Toxicity Pathway Model for 17α-Ethinylestradiol in Early Life Stage Fathead Minnows ().

Environ Sci Technol 2021 04 23;55(8):5024-5036. Epub 2021 Mar 23.

Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B3, Canada.

There is increasing pressure to develop alternative ecotoxicological risk assessment approaches that do not rely on expensive, time-consuming, and ethically questionable live animal testing. This study aimed to develop a comprehensive early life stage toxicity pathway model for the exposure of fish to estrogenic chemicals that is rooted in mechanistic toxicology. Embryo-larval fathead minnows (FHM; ) were exposed to graded concentrations of 17α-ethinylestradiol (water control, 0.01% DMSO, 4, 20, and 100 ng/L) for 32 days. Fish were assessed for transcriptomic and proteomic responses at 4 days post-hatch (dph), and for histological and apical end points at 28 dph. Molecular analyses revealed core responses that were indicative of observed apical outcomes, including biological processes resulting in overproduction of vitellogenin and impairment of visual development. Histological observations indicated accumulation of proteinaceous fluid in liver and kidney tissues, energy depletion, and delayed or suppressed gonad development. Additionally, fish in the 100 ng/L treatment group were smaller than controls. Integration of omics data improved the interpretation of perturbations in early life stage FHM, providing evidence of conservation of toxicity pathways across levels of biological organization. Overall, the mechanism-based embryo-larval FHM model showed promise as a replacement for standard adult live animal tests.
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http://dx.doi.org/10.1021/acs.est.0c05942DOI Listing
April 2021
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