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The objective of this study was to evaluate the toxic effects of progesterone (PF) and estradiol (EF) and the effect of these steroid hormones complexed into cyclodextrins, commercially available drugs, such as micronized progesterone (PM) and transdermal estradiol (ET), and evaluate them as endocrine disruptors through biological parameters of Danio rerio. An acute toxicity test was performed with hormones using D. rerio embryos according to OECD 236 guidelines. The heart rate, mortality, and teratogenic effects were evaluated. In addition, a chronic toxicity test was assayed with adult animals for evaluation of animal behavior, reproductive capacity, and electrophysiological responses of the retina. Analysis of the results of the acute toxicity test with embryos exposed to progestins and estrogens showed that free hormones caused a higher percentage of teratogenic effects such as pericardial edema, yolk sac edema, and spinal deformation. Behavioral evaluation (30-60 days) of adult animals exposed to PM, EF, and ET demonstrated higher frequencies of aggressive behaviors such as Chase away, Persecution, Escape, and Attack. Analysis of reproductive capacity did not show significant differences in the number of viable eggs, and no significant changes were observed in the electrophysiological responses of the retina. According to these results, there is a higher toxicity effect of hormones in the free form when compared to the commercial forms and inclusion complexes. This indicates that complexation into cyclodextrin reduced the toxicity of the hormones according to the parameters studied.

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Marijuana and opioid addictions have increased alarmingly in recent decades, especially in the United States, posing threats to society. When the drug user is a pregnant mother, there is a serious risk to the developing baby. Congenital anomalies are associated with prenatal exposure to marijuana and opioids. Here, we summarize the current data on the prevalence of marijuana and opioid use among the people of the United States, particularly pregnant mothers. We also summarize the current zebrafish studies used to model and understand the effects of these drug exposures during development and to understand the behavioral changes after exposure. Zebrafish experiments recapitulate the drug effects seen in human addicts and the birth defects seen in human babies prenatally exposed to marijuana and opioids. Zebrafish show great potential as an easy and inexpensive model for screening compounds for their ability to mitigate the drug effects, which could lead to new therapeutics.

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