Effects on circulating steroid hormones and gene expression along the hypothalamus-pituitary-gonadal axis in adult Japanese quail exposed to 17β-trenbolone across multiple generations

Abstract

We investigated the effects of the androgenic growth promoter 17β-trenbolone (17βTB) on adult Japanese quail (Coturnix japonica) exposed across three generations. The F0 generation was exposed after sexual maturity to 0, 1, 5, 10, 20, and 40 ppm through feed. The F1 generation was exposed in ovo by maternal transfer and through feed at the same doses as their parents. The F2 generation was exposed in ovo only. Levels of plasma sex steroids, gonadal Cytochrome P450 aromatase (CYP19A1) mRNA and select brain neuroendocrine peptide mRNAs were measured. In males, testosterone levels did not differ in any generation from those in controls. Estradiol was significantly elevated in 17βTB treated F0 and F1 males. In F0 and F1 females, testosterone was suppressed by 17βTB, whereas estradiol was significantly higher at 40 ppm in F0 and at 10 ppm in F1 females. CYP19A1 expression in F1 males and females increased suggesting a compensatory response to the androgenic effects of 17βTB. Few significant effects were observed in the F2 birds indicating that in ovo exposure had limited effects on the monitored endpoints. Overall, our results confirmed endocrine disrupting effects of dietary 17βTB in Japanese quail but the response was dependent on sex, developmental stage at initiation of exposure, and dose.

A critical review of the environmental occurrence and potential effects in aquatic vertebrates of the potent androgen receptor agonist 17β‐trenbolone

“…For example, exposure to 17b-trenbolone decreases sex steroid synthesis, likely through feedback inhibition, which in turn decreases production of vitellogenin in adult females (Figure 1). These alterations subsequently appear to result in a compensatory up-regulation of gene products associated with steroid synthesis (Ekman et al 2011;Karouna-Renier et al 2017). So although responses of mechanistic endpoints associated with HPG function clearly can be highly dynamic, they nonetheless often are consistent with expectations from an HPG systems perspective (Villeneuve et al 2007).…”

“…And even less is known about the toxicity of 17b-trenbolone in nonmammalian vertebrates that might be exposed via contact with soil or ingestion of organisms (e.g., invertebrates) contaminated with 17b-trenbolone. There have been some studies in which Japanese quail were exposed to 17btrenbolone via either the diet or egg injection (see Quinn et al 2007aQuinn et al , 2007bHenry et al 2012;Karouna-Renier et al 2017). The most thorough of these was by Karouna-Renier et al (2017), who conducted a relatively intensive 3-generation assay at doses ranging from 1 to 40 mg 17b-trenbolone/kg feed.…”

“…There have been some studies in which Japanese quail were exposed to 17btrenbolone via either the diet or egg injection (see Quinn et al 2007aQuinn et al , 2007bHenry et al 2012;Karouna-Renier et al 2017). The most thorough of these was by Karouna-Renier et al (2017), who conducted a relatively intensive 3-generation assay at doses ranging from 1 to 40 mg 17b-trenbolone/kg feed. They reported significant decreases in egg production in the F0 and F1 generations at 17b-trenbolone doses of 1 to 5 mg/kg and higher (egg production was not evaluated in the F2), as well as changes in levels of circulating steroids and gene expression consistent with compensatory responses in the HPG axis in response to 17b-trenbolone exposure.…”

Sex‐ and Developmental Stage–Related Differences in the Hepatic Transcriptome of Japanese Quail (Coturnix japonica) Exposed to 17β‐Trenbolone

“…Although in our analysis we did not observe any changes in estrogen receptor expression in males or females, differential expression of the estrogen receptor gene may not be reflective of the downstream effects, and changes in estrogen receptor binding may be a better indicator. A separate analysis of plasma from these quail revealed elevated E2 levels (Karouna‐Renier et al 2017), which is likely responsible for the induction of VTG and APOV1 in adult males. Similar results have been seen in previous studies with fish; exposure of male fathead minnow ( Pimephales promelas ) to 17β‐trenbolone also increased plasma VTG and E2 levels (Ankley et al 2003).…”

“…However, there are no reports on body burden of 17β‐trenbolone in birds in the environment. Whereas effects of 17β‐trenbolone have been well characterized in fish (Ankley et al 2003; Ekman et al 2011; Mizukami‐Murata et al 2016), there have been few studies in avian species, primarily using Japanese quail ( Coturnix japonica ; Quinn et al 2007a; Henry et al 2012; Karouna‐Renier et al 2017). Similar to results in fish, these studies also demonstrated deleterious effects on plasma hormone levels and reproductive behavior, as well as decreased egg production.…”