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目的探讨出生前邻苯二甲酸二(2-乙基己基)酯(DEHP)暴露对成年后仔鼠生殖腺凋亡相关基因表达水平的影响。方法将32只健康SD孕鼠随机分为对照(玉米油)组和2、10、50 mg/kg DEHP染毒组,每组8只。于妊娠第14~19天,采用灌胃方式进行染毒,染毒容量为10 ml/kg,每天1次。仔鼠出生后正常饲养10周,采用实时荧光定量PCR检测睾丸、卵巢组织内B淋巴细胞瘤基因-2(Bcl-2)及Bcl-2相关蛋白(Bax)的RNA表达水平。结果仅10、50 mg/kg DEHP染毒组成年雄性仔鼠睾丸组织内Bcl-2/Bax比值下降,差异均有统计学意义(P<0.05);而各剂量DEHP染毒组成年雄性仔鼠睾丸组织内Bcl-2、Bax基因表达水平均无明显改变(P>0.05)。各剂量DEHP染毒组成年雌性仔鼠卵巢组织中Bcl-2、Bax基因的表达水平以及Bcl-2/Bax值与对照组相比,差异均无统计学意义(P>0.05)。结论出生前暴露DEHP可能通过改变成年后雄性仔鼠睾丸生殖细胞凋亡相关基因Bcl-2/Bax比值,诱导生殖细胞凋亡,该途径可能是其雄性生殖毒性的机制之一。
Objective To investigate the effects of prenatal exposure to dihexyl phthalate (DEHP) on the expression of apoptosis-related genes in germinal gonads of offspring in vitro. Methods Thirty-two healthy SD pregnant rats were randomly divided into control (corn oil) group and 2, 10 and 50 mg / kg DEHP exposure groups, with 8 rats in each group. On the 14th to 19th day of gestation, the rats were drenched by gavage with the capacity of 10 ml / kg once a day. After birth, the offspring mice were fed for 10 weeks, and the mRNA expression of Bcl-2 and Bcl-2 in the testis and ovary were detected by real-time fluorescence quantitative PCR. Results The ratio of Bcl-2 / Bax in testis tissue of male offspring of 10,50 mg / kg DEHP-treated male rats decreased significantly (P <0.05), while the male offspring There was no significant difference in the expression of Bcl-2 and Bax in testis (P> 0.05). The expression levels of Bcl-2 and Bax genes and Bcl-2 / Bax in ovary tissue of female offspring rats in each dose DEHP group had no significant difference compared with the control group (P> 0.05). Conclusion Prenatal exposure to DEHP may induce germ cell apoptosis by changing the Bcl-2 / Bax ratio of germ cell apoptosis-related genes in adult offspring. This pathway may be one of the mechanisms of male reproductive toxicity.