Early life stage trimethyltin exposure induces ADP-ribosylation factor expression and perturbs the vascular system in zebrafish.

Trimethyltin chloride (TMT) is an organotin contaminant, widely detected in aqueous environments, posing potential human and environmental risks. In this study, we utilized the zebrafish model to investigate the impact of transient TMT exposure on developmental progression, angiogenesis, and cardiovascular development. Embryos were waterborne exposed to a wide TMT concentration range from 8 to 96 h post fertilization (hpf). The TMT concentration that led to mortality in 50% of the embryos (LC(50)) at 96 hpf was 8.2 µM; malformations in 50% of the embryos (EC(50)) was 2.8 µM. The predominant response observed in surviving embryos was pericardial edema. Additionally, using the Tg (fli1a: EGFP) y1 transgenic zebrafish line to non-invasively monitor vascular development, TMT exposure led to distinct disarrangements in the vascular system. The most susceptible developmental stage to TMT exposure was between 48 and 72 hpf. High density whole genome microarrays were used to identify the early transcriptional changes following TMT exposure from 48 to 60 hpf or 72 hpf. In total, 459 transcripts were differentially expressed at least 2-fold (P<0.05) by TMT compared to control. Using Ingenuity Pathway Analysis (IPA) tools, it was revealed that the transcripts misregulated by TMT exposure were clustered in numerous categories including metabolic and cardiovascular disease, cellular function, cell death, molecular transport, and physiological development. In situ localization of highly elevated transcripts revealed intense staining of ADP-ribosylation factors arf3 and arf5 in the head, trunk, and tail regions. When arf5 expression was blocked by morpholinos, the zebrafish did not display the prototypical TMT-induced vascular deficits, indicating that the induction of arf5 was necessary for TMT-induced vascular toxicity.

Chronic zebrafish low dose decabrominated diphenyl ether (BDE-209) exposure affected parental gonad development and locomotion in F1 offspring.

Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants around the world. Because of large production volumes, widespread usage and persistence, PBDEs are now ubiquitous environmental pollutants detected in a wide variety of environment media and human samples and therefore pose a significant public health concern. Deca-PBDE (BDE-209) is the only commercial PBDE mixture still allowed for use at present, and has been recently detected at high levels in human samples. However, few studies explore its effect on development, reproduction or neurobehavior with animal models. In particular, studies with long-term chronic exposure at relatively low doses are lacking. In this study, we utilize the zebrafish model to explore the developmental, reproductive, and behavioral toxicities associated with long-term chronic exposure to deca-PBDE (BDE-209). Our findings revealed that long-term chronic exposure to low dose of deca-BDE (ranging from 0.001 to 1 µM) affected overall fitness (measured by condition factor), gonad development, male gamete quantity and quality in F0 parental fish. For F1 offspring without continuous exposure to BDE-209, parental BDE treatment led to delayed hatch and motor neuron development, loose muscle fiber, slow locomotion behavior in normal conditions, and hyperactivity when subjected to light-dark photoperiod stimulation. In conclusion, parental chronic low dose BDE-209 exposure not only affects F0 growth and reproduction, but also elicits neurobehavior alternations in F1 offspring.

Chronic zebrafish PFOS exposure alters sex ratio and maternal related effects in F1 offspring.

Perfluorooctanesulfonic acid (PFOS) is an organic contaminant ubiquitous in the environment, wildlife, and humans. Few studies have assessed its chronic toxicity on aquatic organisms. The present study defined the effects of long-term exposure to PFOS on zebrafish development and reproduction. Specifically, zebrafish at 8 h postfertilization (hpf) were exposed to PFOS at 0, 5, 50, and 250 µg/L for five months. Growth suppression was observed in the 250 µg/L PFOS-treated group. The sex ratio was altered, with a significant female dominance in the high-dose PFOS group. Male gonad development was also impaired in a dose-dependent manner by PFOS exposure. Although female fecundity was not impacted, the F1 embryos derived from high-dose exposed females paired with males without PFOS exposure developed severe deformity at early development stages and resulted in 100% larval mortality at 7 d postfertilization (dpf). Perfluorooctanesulfonic acid quantification in embryos indicated that decreased larval survival in F1 offspring was directly correlated to the PFOS body burden, and larval lethality was attributable to maternal transfer of PFOS to the eggs. Lower-dose parental PFOS exposure did not result in decreased F1 survival; however, the offspring displayed hyperactivity of basal swimming speed in a light-to-dark behavior assessment test. These findings demonstrate that chronic exposure to PFOS adversely impacts embryonic growth, reproduction, and subsequent offspring development.