Di-n-butyl phthalate (DBP) is widely used in consumer products as a plasticizer. Here, we report a natural product taxifolin that can attenuate developmental and reproductive toxicity of DBP. Pregnant rats were daily gavaged with 500 mg/kg DBP alone or together with taxifolin (10 and 20 mg/kg) from gestational day (GD) 12–21. At GD21, sera and testes of male fetus were collected. DBP significantly lowered serum testosterone level at 500 mg/kg and taxifolin can completely reverse its action. DBP caused abnormal aggregation of fetal Leydig cells and taxifolin can reverse it. DBP down-regulated the expression of the genes of cholesterol side-chain cleavage enzyme (Cyp11a1), 17β-hydroxysteroid dehydrogenase 3 (Hsd17b3), and insulin-like 3 (Insl3) and taxifolin can reverse its action. DBP increased malondialdehyde levels and decreased superoxide dismutase and glutathione peroxidase expression and taxifolin can reverse it. DBP increased incidence of multinucleated gonocytes and taxifolin can prevent it. Moreover, DBP lowered sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) and phosphorylated AMP-activated protein kinase (pAMPK) signalling and taxifolin antagonized DBP. In conclusion, in utero exposure to DBP caused developmental/reproductive toxicity of male offspring via increasing reactive oxygen species and taxifolin is an effective food component that completely reverses DBP-mediated action.

邻苯二甲酸二正丁酯（DBP）被广泛用作消费品中的增塑剂。在这里，我们报告了一种天然产物滑石粉，可以减轻DBP的发育和生殖毒性。从妊娠第12–21天起，每天给怀孕的大鼠单独饲喂500 mg / kg DBP或与taxefolin（10和20 mg / kg）一起灌胃。在GD21，收集了男性胎儿的血清和睾丸。DBP可以显着降低500 mg / kg的血清睾丸激素水平，而士福林可以完全逆转其作用。DBP引起胎儿Leydig细胞异常聚集，而taxefolin可以逆转它。DBP下调胆固醇侧链裂解酶（Cyp11a1），17β-羟基类固醇脱氢酶3（Hsd17b3）和胰岛素样3（Insl3）基因的表达），而士福林可以逆转其作用。DBP可增加丙二醛水平，降低超氧化物歧化酶和谷胱甘肽过氧化物酶的表达，而士福林可逆转它。DBP增加了多核促性腺细胞的发生率，而taxefolin可以预防它。此外，DBP降低了sirtuin 1（SIRT1）/过氧化物酶体增殖物激活的受体γ共激活因子1-α（PGC-1α）和磷酸化的AMP激活的蛋白激酶（pAMPK）信号，并且滑石粉拮抗了DBP。总之，在子宫内暴露于DBP会通过增加活性氧来引起雄性后代的发育/生殖毒性，而taxefolin是一种有效的食物成分，可以完全逆转DBP介导的作用。