Neurotransmitters such as dopamine play an important role in reproductive behaviors and signaling. Neuroendocrine-active chemicals in the environment have potential to interfere with and/or alter these processes. A companion study with the dopamine 2 receptor antagonist, haloperidol, found no evidence of a direct effect of the chemical on fish reproduction. This study considered haloperidol's potential effects on behavior and ovarian gene expression. Male fathead minnows exposed to 50 microg haloperidol/L for 96 h were found to be significantly more dominant than control males. In terms of molecular signaling, investigated using oligonucleotide microarrays, there was little similarity in the identity and functions of genes differentially expressed in the ovaries of fathead minnows (Pimephales promelas) versus zebrafish (Danio rerio) exposed under the same conditions. Results suggest that non-lethal concentrations of haloperidol do not induce ovarian molecular responses that could serve as biomarkers of exposure to D2R antagonists, but may impact behavior.

Neurotransmitters such as dopamine play an important role in regulating fish reproduction. However, the potential for neuroendocrine active chemicals to disrupt fish reproduction has not been well studied, despite emerging evidence of their discharge into aquatic environments. This study is the first to apply the fathead minnow 21 d reproduction assay developed for the US Endocrine Disruptor Screening Program to evaluate the reproductive toxicity of a model neuroendocrine active chemical, the dopamine 2 receptor antagonist, haloperidol. Continuous exposure to up to 20 imcrog haloperidol/L had no significant effects on fathead minnow fecundity, secondary sex characteristics, gonad histology, or plasma steroid and vitellogenin concentrations. The only significant effect observed was an increase in gonadotropin-releasing hormone (cGnRH) transcripts in the male brain. Results suggest that non-lethal concentrations of haloperidol do not directly impair fish reproduction. Potential effects of haloperidol on reproductive behaviors and gene expression were examined in a companion study.

A number of environmental contaminants and plant flavonoid compounds have been shown to inhibit the activity of 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerase (3beta-HSD). Because 3beta-HSD plays a critical role in steroid hormone synthesis, inhibition of 3beta-HSD represents a potentially important mode of endocrine disruption that may cause reproductive dysfunction in fish or other vertebrates. The objective of this study was to test the hypothesis that exposure to the model 3beta-HSD inhibitor, trilostane, would adversely affect reproductive success of the fathead minnow (Pimephales promelas). Results of in vitro experiments with fathead minnow ovary tissue demonstrated that trilostane inhibited 17beta-estradiol (E2) production in a concentration- and time-dependent manner, and that the effect was eliminated by providing a substrate (progesterone) that does not require 3beta-HSD activity for conversion to E2. Exposure of fish to trilostane caused a significant reduction in spawning frequency and reduced cumulative egg production over the course of the 21-day test. In females, exposure to 1500 mug trilostane/l reduced plasma vitellogenin concentrations, but did not cause significant histological alterations. In males, average trilostane concentrations as low as 50 mug/l significantly increased testis mass and gonadal somatic index. Trilostane exposure did not influence the abundance of mRNA transcripts coding for 3beta-HSD or other steroidogenesis-regulating proteins in males or females. As a whole, results of this study support the hypothesis that 3beta-HSD inhibition can cause reproductive dysfunction in fish, but did not yield a clear profile of responses at multiple levels of biological organization that could be used to diagnose this mode of action.