2,4-二氯苯氧乙酸对初断乳SD大鼠生殖器官发育的影响及相关机制

Reproductive toxicity of 2,4-dichlorophenoxyacetic acid in immature SD rats

目的:研究2,4-二氯苯氧乙酸(2,4-D)对初断乳SD大鼠生殖器官发育的影响及相关机制。方法:3周龄SPF级SD大鼠80只,随机分为溶剂对照组(1%羧甲基纤维素)和18.125、36.25、72.5 mg/kg 3个2,4-D染毒组,每天经口灌胃1次,连续染毒28 d。试验期间观察并记录动物一般行为,体质量变化及阴道开口时间等指标。染毒结束后,取睾丸、附睾、子宫、卵巢计算湿质量及脏器系数;采用全自动生化仪检测血清中卵泡刺激素(FSH)、促黄体生成素(LH)、雌二醇(E2)、睾酮(T)和胆固醇的含量;采用苏木精-伊红染色法(HE)对大鼠睾丸、附睾、卵巢、子宫进行病理学检测。结果:与对照组比较,至染毒28 d结束时,36.25 mg/kg 2,4-D染毒组雄鼠、72.5 mg/kg组雄鼠和雌鼠体质量均明显降低,差异均有统计学意义(P均<0.05);36.25 mg/kg 2,4-D染毒组阴道开口时间提前,72.5 mg/kg 2,4-D染毒组阴道开口时间延迟且阴道开口率较低,差异具有统计学意义(P<0.05);72.5 mg/kg染毒组血清T水平降低,差异有统计学意义(P<0.05);72.5 mg/kg组雌性SD大鼠胆固醇含量增加,差异有统计学意义(P<0.05);36.25 mg/kg组雌性大鼠血清中E2含量明显增加,而72.5 mg/kg组中E2含量下降,差异均具有统计学意义(P<0.05);光镜下,雄鼠附睾组织曲系精管内(层数)生精细胞较少,72.5 mg/kg 2,4-D染毒组大鼠子宫腔较大,子宫壁较薄。结论:在本实验条件下,2,4-D可干扰大鼠生殖器官的发育,雌性大鼠较雄性明显,其机制可能是抑制胆固醇合成睾酮从而抑制性激素的合成,进而影响生殖系统发育。

OBJECTIVE： To investigate reproductive toxicity of 2,4-dichlorophenoxyaeetic acid （2,4-D） in juvenile male and female SD rats. METHODS： Male and female SD rats were exposed to different concentrations of 2, 4-D for 28 days （18.1, 36.3 and 72.5 mg/kg）, and to a placebo. The general behavior of animals, body weight changes and vaginal opening time were monitored during the period of exposure. After the exposure, the testis, epididymis, uterus, and ovary were weighed to calculate the wet weight and organ coefficient. In addition, blood serum follicle stimulating hormone （FSH）, luteinizing hormone （LH）, estradiol （E2）, testosterone （T） and cholesterol levels were measured using an automatic biochemical analyzer. Pathological examinations were performed on hematoxylin-eosin （HE） stained rat testis, epididymis, ovary and uterus. RESULTS： Compared with the control group, the body weight gain of SD rats decreased significantly with increase of exposure doses （P〈0.05）. The vaginal opening time of the SD rats in the 36.25 mg/kg group was significantly shortened while the vaginal opening time of the SD rats in the 72.5 mg/kg group was significantly prolonged （P〈0.05）. The serum T levels from the 72.5 mg/kg group were decreased compared with the control group （P〈0.05）. The cholesterol levels of female SD rats in the 72.5 mg/kg group w-ere increased （P〈0.05）. The serum E2 levels of female rats in the 36.25 mg/kg group increased significantly, while they were decreased in the 72.5 mg/kg group, and the differences were statistically significant （P〈0.05）. The uterine cavity was larger and the uterine wall was thinner in the rats exposed to 72.5 mg/kg, and the number of spermatogenic cells in the epididymal tissues from the high- dose group was reduced in the seminiferous tubules （layers）. The uterine cavity was larger and the uterine wall was thinner in the rats exposed to 72.5 mg/kg, and the number of spermatogenic cells was reduced in the seminiferous tubules. CONCLUSION ： Our study shows that 2,4-D interfered with development of reproductive system among young SD rats and the female rats were more affected than the males. A possible mechanism is that 2,4-D inhibited the synthesis of sex hormones by inhibiting the synthesis of testosterone from cholesterol, thereby affecting the development of reproductive systems.