Apolipoprotein E Induction in Syrian Hamster Testis Following Tributyltin Exposure: A Potential Mechanism of Male Infertility.

Tributyltin (TBT) is a common environmental contaminant used as the active ingredient in many products such as a biocides, wood preservatives, disinfecting agents, and antifouling paints. The TBT is a known endocrine disruptor. The aim of the current investigation was to determine the toxicity of TBT in the reproductive tract of adult male Syrian hamsters and to ascertain whether this compound results in untoward effects on apolipoprotein E (ApoE), a lipoprotein central to sex hormone synthesis. The TBT was administered orally to male Syrian hamsters at doses of 50, 100, and 150 ppm/kg for 65 days of treatment. We determined body weight, testis weight, sperm count, sperm morphology, testis histology, ApoE expression, serum lipid profile, testosterone level, follicle-stimulating hormone receptor (FSHR), and steroid hormone receptor expression compared to vehicle-treated controls. High doses of TBT significantly affected each of these parameters in Syrian hamsters. Weight and morphology of the testis were altered as well as sperm production. Real-time reverse-transcriptase polymerase chain reaction analysis revealed that expression of ApoE messenger RNA was upregulated in testes from TBT-treated groups compared with controls while the expression of androgen receptor, FSHR, estrogen receptor α (ESR1), and estrogen receptor β (ESR2) was decreased. We posit that exposure to TBT hinders intracellular cholesterol transport resulting in abnormal sex steroid biosynthesis and subsequent spermatogenic defects. Importantly, these effects may account for the decreased level of normal sperm observed in hamsters exposed to TBT.