Gemfibrozil (GEM) and carbamazepine (CBZ) are two environmentally relevant pharmaceuticals and chronic exposure of fish to these compounds has decreased androgen levels and fish reproduction in laboratory studies. The main focus of this study was to examine the effects of GEM and CBZ on testicular steroid production, using zebrafish as a model species. Chronic water borne exposures of adult zebrafish to 10 μg/L of GEM and CBZ were conducted and the dosing was confirmed by chemical analysis of water as 17.5 ± 1.78 and 11.2 ± 1.08 μg/L respectively. A 67 day exposure led to reduced reproductive output and lowered whole body, plasma, and testicular 11-ketotestosterone (11-KT). Testicular production of 11-KT was examined post exposure (42 days) using ex vivo cultures to determine basal and stimulated steroid production. The goal was to ascertain the step impaired in the steroidogenic pathway by each compound. Ex vivo 11-KT production in testes from males chronically exposed to GEM and CBZ was lower than that from unexposed males. Although hCG, 25-OH cholesterol, and pregnenolone stimulation increased 11-KT production in all treatment groups over basal levels, hCG stimulated 11-KT production remained significantly less in testes from exposed males compared to controls. 25-OH cholesterol and pregnenolone stimulated 11-KT production was similar between GEM and control groups but the CBZ group had lower 11-KT production than controls with both stimulants. We therefore propose that chronic GEM and CBZ exposure can reduce production of 11-KT in testes through direct effects independent of mediation through HPG axis. The biochemical processes for steroid production appear un-impacted by GEM exposure; while CBZ exposure may influence steroidogenic enzyme expression or function.

吉非贝齐（GEM）和卡马西平（CBZ）是两种与环境有关的药物，在实验室研究中，鱼类长期接触这些化合物降低了雄激素水平和鱼类繁殖。这项研究的主要重点是使用斑马鱼作为模型物种，研究GEM和CBZ对睾丸类固醇产生的影响。成年斑马鱼的慢性水源性暴露于10μg/ L的GEM和CBZ中，通过水的化学分析确认剂量分别为17.5±1.78和11.2±1.08μg/ L。暴露67天导致生殖能力下降，全身，血浆和睾丸11-酮睾酮（11-KT）降低。在暴露后（42天）使用离体培养物检查11-KT的睾丸生成，以确定基础和刺激性类固醇生成。目的是确定每种化合物在类固醇生成途径中所受的损害。长期暴露于GEM和CBZ的雄性睾丸的离体11-KT产量低于未暴露的雄性。尽管hCG，25-OH胆固醇和孕烯醇酮刺激在所有治疗组中均超过了基础水平，但与对照组相比，暴露于雄性的睾丸中hCG刺激的11-KT产生仍显着减少。GEM和对照组之间25-OH胆固醇和孕烯醇酮刺激的11-KT产生相似，但CBZ组的两种兴奋剂的11-KT产生均低于对照组。因此，我们建议慢性GEM和CBZ暴露可通过独立于通过HPG轴进行介导的直接作用来减少睾丸中11-KT的产生。暴露于GEM不会影响类固醇生产的生化过程。而CBZ暴露可能会影响类固醇生成酶的表达或功能。