Accumulation, Tissue Distribution, and Maternal Transfer of Dietary 2,3,7,8,-Tetrachlorodibenzo-p-Dioxin: Impacts on Reproductive Success of Zebrafish

Abstract

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is a reproductive toxicant and endocrine disruptor in nearly all vertebrates; however, the mechanisms by which TCDD alters the reproductive system is not well understood. The zebrafish provides a powerful vertebrate model system to investigate molecular mechanisms by which TCDD affects the reproductive system, but little is known regarding reproductive toxic response of zebrafish following chronic, sublethal exposure to TCDD. Here we investigate the accumulation of TCDD in selected tissues of adult female zebrafish and maternal transfer to offspring following dietary exposure to TCDD (0.08-2.16 ng TCDD/fish/day). TCDD accumulated in tissues of zebrafish in a dose- and time-dependent manner, except for brain. Chronic dietary exposure resulting in the accumulation of 1.1-36 ng/g fish did not induce an overt toxic response or suppress spawning activity. The ovosomatic index was impacted with an accumulation of as little as 0.6 ng/g fish, and 10% of the females showed signs of ovarian necrosis following accumulation of approximately 3 ng/g TCDD. Offspring health was impacted with an accumulation of as little as 1.1 ng/g female; thus the lowest observed effect level (LOEL) for reproductive toxicity in female zebrafish is approximately 0.6-1.1 ng/g fish. Maternal transfer resulted in the accumulation of 0.094-1.2 ng/g, TCDD, which was sufficient to induce the typical endpoints of larval TCDD toxicity, commonly referred to as blue sac syndrome. This study provides the necessary framework to utilize the zebrafish model system for further investigations into the molecular mechanisms by which TCDD exerts its reproductive toxic responses.