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Microcystin-LR (MC-LR) is a kind of natural toxin which exists widely in aquatic environments and has been reported to be hepatotoxic and carcinogenic. At present, the promoting mechanism of MC-LR on hepatocellular carcinoma (HCC) remains largely unexplored. In this study, the hepatocellular promoting effect of MC-LR was described in Kras

The perfluorooctane sulfonate alternative, F-53B, induces multiple physiological defects but whether it can disrupt eye development is unknown. We exposed zebrafish to F-53B at four different concentrations (0, 0.15, 1.5, and 15 μg/L) for 120 h post-fertilization (hpf). Locomotor behavior, neurotransmitters content, histopathological alterations, morphological changes, cell apoptosis, and retinoic acid signaling were studied. Histology and morphological analyses showed that F-53B induced pathological changes in lens and retina of larvae and eye size were significantly reduced as compared to control. Acridine orange (AO) staining revealed a dose-dependent increase in early apoptosis, accompanied by upregulation of p53, casp-9 and casp-3 genes. Genes related to retinoic acid signaling (aldh1a2), lens developmental (cryaa, crybb, crygn, and mipa) and retinal development (pax6, rx1, gant1, rho, opn1sw and opn1lw) were significantly downregulated. In addition, behavioral responses (swimming speed) were significantly increased, while no significant changes in the neurotransmitters (dopamine and acetylcholine) level were observed. Therefore, in this study we observed that exposure to F-53B inflicted histological and morphological changes in zebrafish larvae eye, induced visual motor dysfunctions, perturbed retinoid signaling and retinal development and ultimately triggering apoptosis.

Tetrachlorobisphenol A (TCBPA), an alternative to tetrabromobisphenol A (TBBPA), is ubiquitous in the environment and could potentially impact the reproductive system of organisms. However, the mechanisms underlying TCBPA-mediated reproductive effects remain unclear. Herein, we exposed Caenorhabditis elegans (C. elegans, L4 larvae) to TCBPA at environmentally relevant doses (0-100 μg/L) for 24 h. Exposure to TCBPA at concentrations of 1-100 μg/L impaired fertility of C. elegans, as indicated by brood size. After staining, the number of germline cells decreased in a dose-dependent manner, whereas germline cell corpses increased in exposed nematodes (10-100 μg/L TCBPA). Moreover, the expression of genes related to the germline apoptosis pathway was regulated following exposure to 100 μg/L TCBPA, indicating the potential role of DNA damage in TCBPA-induced apoptosis. Apoptosis was nearly abolished in ced-4 and ced-3 mutants and blocked in hus-1, egl-1, cep-1, and ced-9 mutants. Numerous foci were detected in TCBPA (100 μg/L)-exposed hus-1::GFP strains. These results indicate that TCBPA induces hus-1-mediated DNA damage and further causes apoptosis via a cep-1-dependent pathway. Our data provide evidence that TCBPA causes reproductive toxicity via DNA damage-induced apoptosis.

Ustiloxin A is a cyclopeptide mycotoxin originally isolated from rice false smut balls (FSBs) that formed in rice spikelets infected by the fungal pathogen Ustilaginoidea virens. Studies have shown that ustiloxin A was toxic to animals, but the toxicological evidence is still lacking. To reveal the negative influence of ustiloxin A on model organism, zebrafish were selected and exposed to ustiloxin A at concentrations of 0, 0.25, 2.5 or 25 μM from 2 h post-fertilization (hpf) to 144 hpf. The hatching rates of embryos in the 25 μM exposure group was 12.85% less than the control group at 96 hpf. Meanwhile, exposure to 0.25, 2.5 or 25 μM ustiloxin A resulted in a distinct dose-dependent increase in mortality rate of embryos at 96 hpf. We also found that exposed to ustiloxin A could cause some other damages on zebrafish larvae, such as growth delay and increased heart rate. In addition, the athletic behavior of zebrafish larvae exposed to ustiloxin A at 25 μM was dramatically different with that of control. Transcriptome sequencing showed that abundances of 339 transcripts (125 up-regulated and 214 down-regulated) were significantly altered in larvae exposed to 25 μM of ustiloxin A. Several of the crucial genes were validated by RT-qPCR. This is the first report on the toxicologic study of ustiloxins against model organism zebrafish. Results suggested that ustiloxins have become a potential danger for food security.

It has been reported that exposure to perfluorooctane sulfonates (PFOS) causes behavioral abnormalities in zebrafish larvae, but the possible mechanisms underlying these changes remain unexplored. In this study, zebrafish embryos (2 h postfertilization, 2-hpf) were exposed to PFOS at different concentrations (0, 0.032, 0.32 and 3.2 mg/L) for 120 h. Developmental endpoints and the locomotion behavior of larvae were evaluated. Reactive oxygen species (ROS) levels, dopamine contents, several genes and proteins related to neurodevelopment and dopamine signaling were examined. Our results indicate that increased ROS levels in the zebrafish larvae heads may be causally associated with neurodevelopment damage. Meanwhile, brain-derived neurotrophic factor (BDNF) and alpha1-Tubulin (α1-Tubulin) protein contents were significantly increased, which may be a compensatory mechanism for the impaired central nervous system. PFOS-induced locomotor hyperactivity was observed in the first light phase and dark phase at the 0.32 and 3.2 mg/L of PFOS. Upregulation of dopamine-related genes tyrosine hydroxylase (th) and dopamine transporter (dat) associated with increased dopamine contents in the 3.2 mg/L of PFOS. In addition, protein expression of TH and DAT were noted at the 0.32 and 3.2 mg/L of PFOS concentrations. Our results suggested that PFOS induces neurobehavioral changes in zebrafish larvae, possibly by perturbing a dopamine signaling pathway. In addition, PFOS induced development damage, such as increased malformation rate and shorter body length.

Triphenyl phosphate (TPHP) is one of the most widely used organophosphate flame retardants (OPFRs) and is frequently detected in a variety of environmental media. Previous studies reported that TPHP had toxic effects on vertebrates, but little toxic information was available in lower trophic aquatic organisms which were more sensitive to the exposure of many toxic substances. In this study, protozoa Tetrahymena thermophila (T. thermophila) were exposed to 0, 0.01, 0.17 or 2.35 mg/L TPHP for 5 days to study the effects of sub-chronic exposure on theoretical population, cell viability, cell size and number of cilia. Additionally, the effects of TPHP on gene transcription were assessed by transcriptome sequencing technique (RNA-Seq). Cell viability and number of cilia were significantly reduced in all TPHP exposure groups compared with the control. In addition, exposure to 0.17 or 2.35 mg/L TPHP significantly reduced the theoretical population, circumference and body width, and there was a significant decrease in body length in the 2.35 mg/L exposure group. Comparative transcriptome sequencing identified a total of 4105 up- and 4487 down-regulated genes after exposure to 2.35 mg/L TPHP for 5 days compared with the control. KEGG analysis showed that dysfunction of pathways associated with ribosome, spliceosome, phagosome, proteasome and protein processing in endoplasmic reticulum in this study might be responsible for the toxicity of T. thermophila caused by TPHP. In general, the results indicated that TPHP had an adverse effect on the protozoa T. thermophila.

The additive flame retardant triphenyl phosphate (TPHP) has been frequently detected in environments and biota. Evidences indicate that TPHP has potential risks to aquatic organisms. Seldom has been reported about its chronic effects to aquatic organism at low trophic levels, such as Cladocera. In the present study,12 h old Daphnia magna (D. magna) were exposed to 0, 5, 50 or 500 μg/L TPHP for 21 days to investigate the chronic effects of TPHP on body length, fecundity and survival. Meanwhile, D. magna PCR arrays were used to evaluate the transcriptional responses of 155 genes involved in 40 pathways. Exposure to 500 μg/L TPHP for 21 days significantly decreased the body lengths of both F0 and F1 generation and inhibited the fecundity of F0 generation. Results of RT-qPCR showed that the expressions of 76 genes involved in 15 pathways were significantly altered after exposure to 500 μg/L TPHP for 21 days. The significantly altered pathways related to genetic information processing, cellular process and metabolism might be responsible for the observed effects of TPHP. Overall, our results showed that chronic exposure to TPHP caused developmental and reproductive toxicities to D. magna.

Microcystin-LR (MC-LR) is widely distributed in the natural environment and causes hepatotoxicity. However, whether MC-LR promotes liver tumor progression remains controversial. krasV12 transgenic zebrafish were used as an inducible liver tumor model to evaluate the potential tumor-promoting effect of MC-LR. First, krasV12 transgenic larvae were exposed to 0, 0.1 and 1 mg/L MC-LR with 20 mg/L doxycycline (Dox) for 4 d. The gray values and histopathological examinations of the liver demonstrated that MC-LR aggravated liver tumor progression, which could be inhibited by the Protein arginine methyltransferase 5 (Prmt5) inhibitor compound 5 (CMP5). Second, 1-month-old juvenile transgenic zebrafish were exposed to 0, 20 mg/L Dox, 1 μg/L MC-LR, and 20 mg/L Dox with 0.1 or 1 μg/L MC-LR for 15 d to determine whether the exposure to environmental concentrations of MC-LR promoted hepatocellular carcinoma (HCC) progression. We found that environmental concentrations of MC-LR increased the hepatosomatic index (HSI) and gray value (intensity/area) and promoted HCC progression. The results indicate that environmental concentrations of MC-LR have the potential to promote liver tumor progression. Taken together, the present study demonstrates that MC-LR can promote tumor in krasV12 transgenic zebrafish and that the upregulation of prmt5 expression might contribute to MC-LR-mediated promotion of liver tumorigenesis.

Microplastics (MPs), emerging environmental contaminants, exhibit multiple toxicities in organisms. However, the transgenerational neurotoxicity of MPs has received little attention. Caenorhabditis elegans has been used as a model organism for studying transgenerational toxicity. In this study, the transgenerational neurotoxicity and oxidative stress of MPs were investigated over five generations (F0–F4) of C. elegans. The parental generation (F0) was exposed to polystyrene microplastics (PS-MPs) at concentrations of 0.1–100 μg/L, and subsequent generations (F1–F4) were cultured under toxicant-free conditions. The results indicated that exposure to PS-MPs at concentrations of 10–100 μg/L significantly decreased head thrash and body bends in nematodes, and this reduction was also observed in subsequent generations (F1–F2). This suggested that neurotoxicity induced by PS-MPs can be transferred from the parent to subsequent generations. Maternal exposure to 100 μg/L PS-MPs significantly enhanced ROS production and lipofuscin accumulation in subsequent generations (F1–F2), indicating that the induction of oxidative stress plays an important role in the transgenerational neurotoxicity in C. elegans. Moreover, maternal exposure to PS-MPs resulted in the transgenerational upregulation of genes related to oxidative stress (clk-1, ctl-1, sod-3, sod-4, and sod-5) in the F1–F3 generations, which indicated that these genes may be involved in regulating transgenerational neurotoxicity in C. elegans.

Decabromodiphenyl ether (BDE-209) was one of most widely-used polybrominated diphenyl ether (PBDE) flame retardants and is frequently detected in both abiotic and biotic samples from environment. However, knowledge of its transgenerational risks is limited. Here, 4-month-old zebrafish were exposed to various concentrations of BDE-209 (0, 3, 30 or 300μg/L) for 28days and spawned in clean water without BDE-209. Concentrations of triiodothyronine (T3) and thyroxine (T4) as well as expressions of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis were measured in offspring after exposure of adult zebrafish to BDE-209. BDE-209 was accumulated in adult fish and F1 eggs, which suggests transfer of this compound from adult fish to their offspring. Exposure of BDE-209 to parents resulted in developmental abnormalities in offspring and a significant decrease in T4 concentrations in F1 larvae 120h post-fertilization (hpf). Furthermore, expressions of several genes involved in the HPT axis were also altered. Expressions of thyroid hormone receptor α (tr-α), thyrotropin releasing hormone (trh), thyroid stimulating hormone β (tsh-β) and deiodinase 1 (dio 1) were significantly down-regulated in F1 individuals, while expressions of thyroid stimulating hormone receptor (tshr) and transthyretin (ttr) were significantly up-regulated. These results suggest that exposure of parent zebrafish to BDE-209 can cause developmental toxicity in offspring and disruption of the thyroid endocrine system of offspring.

Microcystin-LR (MCLR) was commonly regarded as a potent hepatotoxin and has been reported to cause neurotoxicity. This study was aimed to investigate how maternal MCLR exposure during pregnancy alters behavioral responses in offspring mice and the possible molecular mechanism involved in this procedure. Three doses of MCLR solutions (0, 3 or 15 μg/kg body weight) were administered subcutaneously to pregnant C57bl/6 from gestation day (GD) 6–19. Our results showed that MCLR prenatal exposure led to the impairment of learning and memory function in offspring on postnatal days (PND) 35, accompanied by endoplasmic reticulum (ER) stress and neuronal apoptosis in hippocampal CA1 regions of mice. Sixteen miRNAs in hippocampus of pups on PND 35 were significantly affected by MCLR exposure with the markedly decreased transcription of miR-181a-5p. We then found that miR-181a-5p was down-regulated, accompanied by activation of ER stress after prenatal exposure to MCLR using qPCR analysis. Furthermore, glucose-regulated protein, 78kDa/binding immunoglobulin protein (Grp78/BIP), a major ER chaperone and signaling regulator, was identified as a target of miR-181a-5p. Our study showed that miR-181a could lead to a decrease in the mRNA expression and protein levels of Grp78 by directly binding to its 3′-untranslated region (3′-UTR) in primary hippocampal neurons. Our findings indicate that the up-regulation of Grp78 mediated by inhibition of miR-181a-5p is a possible mechanism resulting in ER stress and cognitive impairment in pups following prenatal MCLR exposure.

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) has been detected in various environmental media and has been implicated as a weak mutagen or carcinogen, but whether TDCIPP can promote the progression of liver tumor remains unclear. In this study, kras

Inconel 625 superalloy samples were fabricated using wire arc additive manufacturing (WAAM). The phase composition, microstructure, anti-corrosion, and mechanical properties of the Inconel 625 WAAM samples were analyzed. The microstructure of the Inconel 625 WAAM alloy showed good forming quality, no defects, and good metallurgical bonding within the specimens. The metallographic structure exhibited primarily γ-Ni and granular precipitated phases; the average microhardness of the transverse and longitudinal cross-sections of the sample was 243.5 and 243.3 HV0.1, respectively. Yield and tensile strength as well as elongation, decrease in area, and the room-temperature impact values of this alloy were equal to 450 and 736 MPa, 38% and 52%, and 152 J, respectively. The intergranular corrosion test results indicated that the average corrosion rate of the sample is 0.609 mm/year, indicating excellent resistance to intergranular corrosion.

Several mechanisms regarding the developmental and reproductive toxicity of l -selenomethionine (SeMet) in freshwater fish have been widely reported. However, limited information was available on endocrine-disrupting effects of SeMet. In this study, zebrafish larvae (day 24 post-fertilization) were exposed to environmentally-relevant levels of dietary SeMet (control, 1.11 ± 0.11, 3.59 ± 0.20, 10.80 ± 0.52, 29.19 ± 0.46, and 58.63 ± 0.70 μg Se/g d.w. diet) for 90 days until sexual maturity. For the first time, a gender difference in the effect of SeMet on body mass of zebrafish was observed. The lowest observed adverse effect level (LOAEL) in male was 10.80 ± 0.52 μg Se/g d.w., while it was 29.19 ± 0.46 μg Se/g d.w. in female. Chronic exposure to dietary SeMet reduced the percentage of early vitellogenic oocyte in female and the percentage of spermatid in male by inhibiting the growth hormone/insulin-like growth factors (GH/IGFs) and hypothalamus-pituitary-gonad (HPG) systems, which was characterized by significant decreases in the transcriptional levels of gh, igf1, era, and ar. Se content in the liver of male was significantly higher than that in female when dietary Se level reached 10.80 ± 0.52 μg Se/g d.w.. Furthermore, the zinc content in the livers and gonads of both female and male treated with 29.19 ± 0.46 and 58.63 ± 0.70 μg Se/g d.w. diets was significantly reduced. Reduction of zinc ion not only led to the significantly upregulated transcriptional levels of zip1 and znt2, but also downregulated transcriptional levels of znf219l and sp7. In summary, this study provides a new evidence that chronic exposure to high level of dietary SeMet (≥10.80 μg Se/g d.w.) could impair the development and reproduction of zebrafish with gender difference by interfering the GH/IGFs and HPG systems. Moreover, disruption of zinc ion homeostasis might exacerbate the toxicity of Se to zebrafish.

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) has been detected in various environmental media and has been implicated as a weak mutagen or carcinogen, but whether TDCIPP can promote the progression of liver tumor remains unclear. In this study, krasV12 genetically modified zebrafish, Tg(fabp10:rtTA2s-M2; TRE2:EGFP-krasG12V), a model system in which liver tumors can be induced by doxycycline (DOX), was used to evaluate the liver tumor promotion potential of TDCIPP. Briefly, krasV12 transgenic females were exposed to 0.3 mg/L TDCIPP, 20 mg/L DOX or a binary mixture of 0.3 mg/L TDCIPP with 20 mg/L DOX, and liver size, histopathology, and transcriptional profiles of liver were determined. Treatment with TDCIPP resulted in increased liver size and caused more aggressive hepatocellular carcinoma (HCC). Compared with the exposure to DOX, TDCIPP in the presence of DOX up-regulated the expression of genes relevant with salmonella infection and the toll-like receptor signaling pathway. These results implied an occurrence of inflammatory reaction, which was sustained by the increase in the amount of infiltrated neutrophils in the liver of Tg(lyz:DsRed2) transgenic zebrafish larvae whose neutrophils were labelled by red fluorescent protein under the lysozyme C promoter. Furthermore, compared with the binary exposure of DOX and TDCIPP, treatment with a ternary mixture of TDCIPP, DOX and inflammatory response inhibitor (ketoprofen) significantly decrease the liver size and the amounts of neutrophils in the livers of kras and lyz double transgenic zebrafish larvae. Collectively, our results suggested that TDCIPP could promote the liver tumor progression by induction of hepatic inflammatory responses.

Growth hormone/insulin-like growth factors (GH/IGFs) axis PCR array of zebrafish (Danio rerio) larvae was developed based on the quantification of mRNA expressions of 19 genes that were confirmed to play vital roles in the regulation of fish growth. Zebrafish embryos were exposed to each of four concentrations of the six representative chemicals, bisphenol A (BPA), perfluorooctane sulfonates (PFOS), tris (1,3-dichloroisopropyl) phosphate (TDCIPP), cadmium chloride (CdCl2), mercury (II) chloride (HgCl2) and lead (II) acetate (PbAc) from 2 h post fertilization (hpf) to 96 hpf. Developmental endpoints and transcriptional profiles of the genes involved in GH/IGFs axis of zebrafish larvae were examined at 96 hpf. Body length of zebrfish larvae was found to be a more susceptible endpoint in zebrafish embryo toxicity test than other endpoints, including survival rate, hatching rate, malformation incidence and heart rate after exposure to each of those representative chemicals selected. Perturbation of mRNA expressions of GH/IGF axis genes accompanied by decreased body length indicated that indicated that the growth inhibition observed might be attributed to the dysregulation of GH/IGFs axis. Therefore, GH/IGF axis PCR array of zebrafish larvae could be used to evaluate the effects of chemicals on GH/IGF endocrine system.

Tris (2-butoxyethyl) phosphate (TBOEP) is widely used as a substitute of polybrominated diphenyl ethers (PBDEs). It has been frequently measured at concentrations of micrograms per liter (μg/L) in surface waters and waste water. However, limited information is available about the reproduction toxicology of TBOEP. In this study, adult zebrafish pairs were exposed to TBOEP at concentrations of 0, 5, 50, and 500μg/L for 21days. The effects on reproduction, hormone concentration, transcription of genes along the hypothalamic-pituitary-gonadal (HPG) axis, and gonadal development were investigated. After exposure to TBOEP, plasma concentrations of 17β-estradiol were significantly increased in both sexes of fish, while increase of testosterone was observed only in male fish. Transcription of genes along the HPG axis was significantly influenced by exposure to TBOEP in both male and female fish. Moreover, TBOEP decreases the average number of eggs production, as well as hatching success and survival rates in offspring. Histological examination shows inhibition of oocyte maturation in females and retardation spermiation in males, respectively. The results demonstrate that TBOEP could disturb the sex hormone balance by altering regulatory circuits of the HPG axis, affect gonadal development, eventually leading to disruption of reproductive performance and the development of progeny.

Recent studies have demonstrated that cyanobacteria-derived Microcystin-LR (MC-LR) can cause developmental toxicity and trigger apoptosis in zebrafish (Danio rerio) larvae, but the underlying mechanisms remain largely unknown. In this study, we tested the hypothesis that the mechanism by which MC-LR induces developmental toxicity is through activation of endoplasmic reticulum (ER) stress. MC-LR (4.0 μM) exposure through submersion caused serious developmental toxicity, such as malformation, growth delay and decreased heart rates in zebrafish larvae, which could be inhibited by ER stress blocker, tauroursodeoxycholic acid (TUDCA, 20 μM). Meanwhile, acridine orange (AO) staining showed TUDCA could rescue cell apoptosis in heart area in zebrafish larvae resulted by MC-LR exposure. Real-time polymerase chain reaction (real-time PCR) analysis demonstrated that MC-LR induced activation of ER stress which consequently triggered apoptosis in zebrafish larvae. Protein expression examined by western blot indicated that MC-LR could activate MAPK8/Bcl-2/Bax pathway and caspase-dependent apoptotic pathway in zebrafish larva and the effects were mitigated by inhibition of ER stress. Taken together, the results observed in this study suggested that ER stress plays a critical role in developmental toxicity and apoptosis in zebrafish embryos exposed to MC-LR.

A PCR array, based on expression of genes along the hypothalamic-pituitary-gonadal-liver (HPGL) axis of fish, has been suggested as a useful method for screening of endocrine-disrupting chemicals (EDCs). However, effects of circadian rhythm on responses of the HPGL axis to exposure to chemicals were unknown. In this study, profiles of expression of genes along the HPGL axis and concentrations of 17β-estradiol (E2) in blood plasma of female zebrafish were compared at two sampling times of day (8:00 AM and 7:00 PM). Prochloraz (PCZ) was selected as a model chemical to evaluate differences in responses of the HPGL axis at these two times of day. Profiles of responses of concentrations of E2 in plasma and expressions of genes along the HPGL axis genes were different between the two times of sampling. Concentrations of E2 were less, and abundances of mRNA for several genes along the HPGL axis were significantly greater or lesser when samples were collected at 7:00 PM than they were when samples were collected at 8:00 AM. Exposure to three concentrations of PCZ (3, 30 or 300μg/L) for 48h resulted in significantly lesser concentrations of plasma E2 and caused compensatory up-regulation of genes included in hypothalamus, pituitary and ovary. Expressions of genes along the HPGL were more responsive to PCZ at 8:00 AM than they were when samples were collected at 7:00 PM. Correlations among parameters in samples collected at the two times indicated the effects might be due to different concentrations of E2 in plasma due to exposure to PCZ.

Microcystin-LR (MCLR) is a commonly acting potent hepatotoxin and has been pointed out of potentially causing neurotoxicity, but the exact mechanisms of action still remain unclear. Using proteomic analysis, forty-five proteins were identified to be significantly altered in hippocampal neurons of rats treated with MCLR. Among them, Ca2+-activated phosphatase calcineurin (CaN) and the nuclear factor of activated T-cells isoform c3 (NFATc3) were up-regulated remarkably. Validation of the changes in CaN and NFATc3 expression by Western blotting demonstrated CaN cleavage and subsequent NFATc3 nuclear translocation were generated, suggesting that exposure to MCLR leads to activation of CaN, which in turn activates NFATc3. Activation of CaN signaling has been reported to result in apoptosis via dephosphorylation of the proapoptotic Bcl-2 family member Bad. In agreement with this, our results revealed that treatment of neurons with the CaN inhibitor FK506 blocked the reduction in Bad dephosphorylation and cytochrome c (cyt c) release triggered by MCLR. Consistent with these biochemical results, we observed a marked decrease in apoptotic and necrotic cell death after MCLR exposure in the presence of FK506, supporting the hypothesis that MCLR appeared to cause neuronal toxicity by activation of CaN and the CaN-mediated mitochondrial apoptotic pathway.

Compensation responses and adaptability of hypothalamic-pituitary-gonadal (HPG) axis have been reported in fish exposed to model chemicals, however due to its importance in predictive toxicology further study was needed to elucidate details of the integrated responses to model chemicals. Transcriptional profiles of the hypothalamic-pituitary-gonadal (HPG) axis and concentrations of 17β-estradiol (E2) in plasma were measured in male and female zebrafish that had been exposed to one of seven concentrations of the fungicide, prochloraz: low (1, 3 or 10μg/L), medium (30 or 100μg/L) or high concentrations (300 or 1000μg/L) for 4 days. In zebrafish exposed to the low and medium concentrations of prochloraz, compensation responses of the HPG axis through transcription, occurred in brain (up-regulation of gnrh, gnrhr and lhβ) and both brain and gonad (up-regulation of steroidogenic genes), respectively. Concentrations of E2 in plasma and expression of estrogen receptor 1 (er1) and vitellogenins (vtgs) in liver did not change. This result suggested that compensatory responses were successful in maintaining homeostasis. In zebrafish exposed to the two greatest concentrations, compensatory responses occurred in brain, gonad and liver through up-regulation of er2β, but it failed to maintain concentration of E2 in blood plasma and expression of er1 and vtgs in liver. Collectedly, the results observed in this study allowed characterization of dose-dependent compensatory responses along the HPG axis and liver and identified key linkages between compensatory responses occurring in brain, gonad and liver after exposure to prochloraz.