Prenatal exposure to di-n-butyl phthalate induces erectile dysfunction in male adult rats
Prenatal exposure to di-n-butyl phthalate induces erectile dysfunction in male adult rats
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产前接触邻苯二甲酸二正丁酯会导致雄性成年大鼠勃起功能障碍
DOI：
10.1016/j.ecoenv.2021.112323
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发表时间：
2021-05-18
影响因子：
6.8
通讯作者：
Wang，Shangqian
中科院分区：
文献类型：
--
作者：
Zhou，Xiang;Zhang，Tongtong;Wang，Shangqian
邻苯二甲酸二正丁酯（DBP）是一种广泛使用的增塑剂，也是一种环境内分泌干扰化合物。然而，产前接触 DBP 是否会损害勃起功能仍不清楚。我们进行这项研究是为了调查产前暴露于 DBP 对勃起功能的潜在影响及其潜在机制。建立了产前 DBP 暴露的大鼠模型（在妊娠第 13-21 天期间灌胃，每天 12.5、100 或 800 mg/kg）。产前暴露 DBP 显着降低 10 周龄雄性大鼠的阴茎/体重比、海绵体神经髓鞘厚度和血清睾酮水平。此外，所有DBP暴露组均检测到勃起功能障碍，转化生长因子-β1（TGF-β1）表达显着增加，α平滑肌肌动蛋白（α-SMA）、神经元和内皮一氧化氮合酶（nNOS和eNOS）表达减少。此外，与对照组相比，磷酸 B 细胞淋巴瘤 2 (Bcl-2) 相关死亡启动子 (p-Bad)/Bad 和磷酸蛋白激酶 B (p-AKT)/AKT 比率显着降低，但 Bcl-2 相关 X 蛋白 (Bax)/Bcl-2 比率和 caspase-3 高于对照组。值得注意的是，产前接触 DBP 会增加雄性成年大鼠患 ED 的风险，即使服用低剂量的 DBP（12.5 毫克/公斤/天）也是如此。 DBP 暴露导致阴茎纤维化、睾酮水平降低和内皮功能障碍，可能通过激活阴茎中的 Akt/Bad/Bax/caspase-3 通路并抑制 NOS/cGMP 通路而导致 ED。
Di-n-butyl phthalate (DBP) is a widely used plasticizer and an environmental endocrine-disrupting compound. However, whether prenatal exposure to DBP can impair erectile function remains unknown. We conducted this study to investigate the potential effects of prenatal exposure to DBP on erectile function and the underlying mechanisms. A rat model of prenatal DBP exposure (12.5, 100 or 800 mg/kg/day by gavage during gestational days 13–21) was established. Prenatal DBP exposure significantly decreased penis/body weight ratio, myelin sheath thickness of cavernosum nerves and serum testosterone level in male rats at the age of 10 weeks. Furthermore, erectile dysfunction was detected in all DBP exposure groups, which exhibited substantial increases in transforming growth factor-β1 (TGF-β1) expression and decreases in the expression of alpha smooth muscle actin (α-SMA), neuronal and endothelial nitric oxide synthase (nNOS and eNOS). Additionally, the phospho-B-cell lymphoma 2 (Bcl-2)-associated death promoter (p-Bad)/Bad and phospho-the protein kinase B (p-AKT)/AKT ratios were remarkably lower, but the Bcl-2-associated X protein (Bax)/Bcl-2 ratio and caspase-3 were higher in DBP exposure groups than in the control group. Notably, prenatal exposure to DBP increase the risk of ED in male adult rats, even taking low dose of DBP (12.5 mg/kg/day). DBP exposure causing penile fibrosis, decreased testosterone level, and endothelial dysfunction may be responsible for ED by activating Akt/Bad/Bax/caspase-3 pathway and suppressing NOS/cGMP pathway in penis.