Department of Anesthesiology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Department of Pharmacy, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Toxicol Lett. 2019 Oct 10;314:53-62. doi: 10.1016/j.toxlet.2019.07.016. Epub 2019 Jul 15.
Benzyl butyl phthalate (BBP) is a widely used plasticizer and has raised public health concerns. Here, we report the effects of BBP on the testis development during rat puberty. BBP (0, 10, 100 or 1000 mg/kg) was gavaged to 35-day-old male Sprague Dawley rats for 21 days. The serum testosterone levels, Leydig cell number, the expressions of Leydig and Sertoli cell genes and proteins were measured. The in vitro effects on steroidogenesis and gene expression in immature Leydig cells were observed. BBP significantly increased serum testosterone level at 10 mg/kg but lowered its level at 1000 mg/kg without affecting serum luteinizing hormone and follicle-stimulating hormone levels. BBP increased Leydig cell number at all doses but inhibited steroidogenic capacity per Leydig cell at 1000 mg/kg. BBP significantly increased the ratio of phosphos-AKT2 (pAKT2)/AKT2, and phosphos-ERK1/2 (pERK1/2)/ERK1/2 in the testis. Mono-benzyl phthalate (the metabolite of BBP) inhibited steroidogenesis but BBP did not affect androgen production in immature Leydig cells in vitro. In conclusion, BBP non-linearly regulates Leydig cell development by increasing Leydig cell number but inhibiting steroidogenesis.
邻苯二甲酸丁基苄基酯（BBP）是一种广泛使用的增塑剂，引起了公众对健康的关注。在这里，我们报告了 BBP 对青春期大鼠睾丸发育的影响。将 BBP（0、10、100 或 1000mg/kg）灌胃给 35 天大的雄性 Sprague Dawley 大鼠 21 天。测量血清睾酮水平、Leydig 细胞数量、Leydig 和支持细胞基因和蛋白的表达。观察了 BBP 对未成熟 Leydig 细胞类固醇生成和基因表达的体外影响。BBP 在 10mg/kg 时显著增加血清睾酮水平，但在 1000mg/kg 时降低其水平，而不影响血清黄体生成素和卵泡刺激素水平。BBP 增加了所有剂量的 Leydig 细胞数量，但抑制了 1000mg/kg 时每个 Leydig 细胞的类固醇生成能力。BBP 显著增加了睾丸中磷酸化-AKT2（pAKT2）/AKT2 和磷酸化-ERK1/2（pERK1/2）/ERK1/2 的比值。单苄基邻苯二甲酸酯（BBP 的代谢物）抑制类固醇生成，但 BBP 并未影响体外未成熟 Leydig 细胞中的雄激素产生。总之，BBP 通过增加 Leydig 细胞数量但抑制类固醇生成来非线性质控 Leydig 细胞发育。
