低剂量2,3,7,8-四氯二苯并对二噁英宫内暴露对仔鼠卵巢功能的影响

Gestatlonal exposure to mild dosesof 2,3,7,8-tetrachlorodib-enzo-p-dioxin （TCDD） disrupts ovarian function in neonatal rats

目的 探讨2,3,7,8-四氯二苯并对二噁英（TCDD）宫内暴露对新生雌鼠早期卵巢功能的影响.方法 母鼠妊娠第13天（GD3）始每2天灌胃5、100、500 ng/kg TCDD.ECLIA法测定出生后3天（PND3）仔鼠雌二醇（E2）和孕酮（P）水平.采用石蜡切片及HE染色、透射电镜观察PND3仔鼠卵巢组织学变化,对原始卵泡和初级卵泡进行计数. 结果 500 ng/kg组的仔鼠血清E2和P水平[（5.4±0.4） pg/ml、（35.4±3.2） pg/ml]下降,与其他组比较,差异有统计学意义.各剂量组的原始卵泡、初级卵泡计数无差异;HE切片提示TCDD暴露后仔鼠卵巢组织有不同程度的病理改变,500 ng/kg组的毒性作用更为显著,透射电镜下可见初级卵母细胞变小、细胞核固缩,细胞器不清;颗粒细胞结构破坏,不完整. 结论 TCDD低剂量宫内暴露明显损害PND3仔鼠卵泡的超微结构、干扰卵巢雌二醇和孕酮的分泌,对子代雌鼠卵巢有毒性作用。

Objective The objectives of this study were to investigate the effects of exposure to TCDD in utero on early ovarian function in neonatal female rats. Methods Beginning at gestational day 13 （GD13）, female SD rats were intragastric administrated with a range of low-doses of TCDD （5, 100, and 500 ng/kg/2d） or coin oil until labor every two days. Serum concentrations of estradiol and progesterone at postnatal day 3 （PND3） rats were measured with the electro- chemiluminescence immunoassay （ECLIA）. Ovarian morphology and ultrastructure of PND3 rats were observed using HE- stain and transmission electron microscope. The number of primordial follicles and primary follicles were counted. Results TCDD treatment decreased serum Estradiol 2 （ E2 ） and Progesterone （P） concentrations [ （5.4 ± 0. 4） pg/ml and （ 35.4 ± 3.2） pg/ml, respectively~ of PND3 pups. There were significant differences in serum E2 and P concentrations in female between 500 ng/kg/2d and other groups. No differences in numbers of primordial follicles and primary follicles were found between the control and TCDD treated groups. Ovarian structure of the female pup was affected pathologically, and the harmful effects were significance in 500 ng/kg/2d group. The main ultrastructural findings related to the eocytes of the experimental group were shrunk, pyknotic nuclei, and degenerative mitochondria in the ooplasm. Furthermore, the granulosa cells revealed disorganization and integrity. Conclusion Gestational exposure to mild dosage of TCDD significantly perturbs ovarian uhrastructure and endocrine in PND3 female rats. TCDD exposure in utero had dramatically reproductive toxicity effects on ovary of neonatal pups.