邻苯二甲酸二乙基己酯及代谢产物邻苯二酸-单-2-乙基己酯对雄性幼鼠生精细胞凋亡的影响

目的了解环境内分泌干扰因子邻苯二甲酸二乙基已酯（DEHP）及代谢产物邻苯二酸-单-2-乙基己酯（MEHP）对雄性幼鼠
生精细胞凋亡有否影响。方法生后2周龄的Wistar雄性幼鼠98只，随机分为14组，7只/组。随机选择1组行生理盐水（0.9%
NS0.2ml·kg-1 ·d-1）灌胃喂养3周，作为正常对照组（NC组）；再选1组行环磷酰胺（CTX100mg·kg
-1 ·d-1）灌胃喂养1周，作为阳性对照组（PC组）；余各组分别用DEHP、MEHP按低剂量（100mg·kg
-1 ·d-1）、中剂量（200mg·kg-1 ·d-1）、高剂量（300mg·kg-1 ·d-1）灌胃喂养1周；以及分别按低剂量（100mg·kg
-1 ·d-1）灌胃喂养1、2、3周分组，建立动物模型。观察不同时期、不同剂量下睾丸生精细胞
的形态学变化，并应用TUNEL法检查睾丸生精细胞凋亡情况，放射免疫法检测血清性激素（卵泡刺激素FSH、黄体生成素LH以
及睾酮T）水平。结果（1）睾丸生精细胞的变化：用药组生精细胞萎缩、发育落后、数量少，线粒体肿胀、空泡化等；在喂养1周的
不同剂量组内，随剂量增加生精细胞损害加重，在低剂量不同喂养时间组内，随喂养时间的延长生精细胞损害亦加重；（ 2）睾丸
组织中生精细胞凋亡：与NC组比较，用药组生精细胞凋亡显著增多（P<0.01）；在喂养1周的不同剂量组内、以及低剂量不同喂
养时间组内生精细胞凋亡间比较，差异均有统计学意义（P<0.05）；（3）血清性激素水平：与NC组比较，用药组FSH、LH水平升
高，T水平下降（P<0.05）；在喂养1周的不同剂量组内、以及低剂量不同喂养时间组内性激素水平间比较，差异也有统计学意义
（P<0.05）。结论DEHP及代谢产物MEHP对幼鼠生精细胞凋亡有明显影响，且呈时间-量效依赖效应。

Effect of di-(2-ethylhexyl)phthalate and its metabolite mono(2-ethylhexyl)phthalate on spermatogenic cell apoptosis in young male Wistar rats

ObjectiveTo explore the influences of di-(2-ethylhexyl)phthalate (DEHP) and its principle metabolite mono
(2-ethylhexyl)phthalate (MEHP) on spermatogenic cell apoptosis in young male Wistar rats.MethodsNinety-eight2-week-old
male Wistar rats were randomly divided into14equal groups to receive daily intragastric administration of0.2ml/kg normal
saline for3weeks (normal control),100mg/kg cyclophosphamide (CTX) for1week (positive control),100, 200, and 300mg/kg
DEHP or MEHP for1week, or100mg/kg DEHP or MEHP for1, 2, and 3weeks. After the treatments, the pathological changes
of the testicular tissues were examined, spermatogenic cell apoptosis was detected, and serum sex hormones levels were
measured using TUNEL assay or radioimmunoassays.ResultsCTX, DEHP, and MEHP all caused shrinkage, development
retardation and quantitative reduction of spermatogenic cells with and mitochondrial swelling vacuolar changes. The damage
of spermatogenic cells increased significantly with the increment of DEHP and MEHP doses and exposure time. Both DEHP
and MEHP treatments resulted in significantly increased cell apoptosis index (AI) in close correlation with the exposure doses
and duration (P<0.01). DEHP and MEHP treatments also significantly increased serum levels of follicle stimulating hormone
and luteinizing hormone and decreased testosterone levels in a dose- and time-dependent manner (P<0.05).ConclusionDEHP
and MEHP can induce obvious apoptosis of spermatogenic cells in young male rats with a dose- and time-dependent effect.