目的探讨早期低剂量接触全氟辛烷磺酸盐(perfluorooctane sulfonate,PFOS)对大鼠生殖功能和生长发育的影响及S-腺苷L-甲硫氨酸(S adenosyl L methionine,SAM)和5-杂氯脱氧胞嘧啶(decitabine,DAC)对其的干预作用。方法将40只健康出生5 d(PND5)SPF级SD大鼠随机分为4组,每组10只,雌雄各半,分别为对照(0.2%Tween-80生理盐水)组、PFOS染毒组、SAM干预组和DAC干预组。PFOS染毒组、SAM干预组和DAC干预组分别染毒5 mg/kg的PFOS;SAM干预组和DAC干预组分别同时给与16 mg/kg的SAM和0.15 mg/kg的DAC干预;采用颈部皮下注射方式进行染毒,每天1次,28 d后,每3 d 1次,持续染毒至出生后60 d(PND60)。每天观察F0代大鼠的一般情况并测定体重。待F0代大鼠成年后,将雌、雄大鼠按1∶1合笼交配。待F1代大鼠成年后,各组选取6只大鼠,以雌∶雄为2∶1进行合笼,孕期和哺乳期(PND28)母鼠的染毒方法同前。观察各代大鼠的生育能力和仔鼠的发育情况,并观察F1代大鼠睾丸组织形态结构变化。结果与对照组比较,PFOS组、SAM干预组和DAC干预组F0代母鼠的受孕率均较低,死产率较高,存活率较低;PFOS组和DAC干预组F0代母鼠的畸胎率和产后死亡率均较高,差异均有统计学意义(P<0.01,P<0.05)。与PFOS染毒组比较,SAM干预组F0代母鼠的受孕率、存活率较高,死产率、畸胎率较低;DAC干预组F0代母鼠的死产率、存活率较低,产后死亡率较高,差异均有统计学意义(P<0.01,P<0.05)。与对照组比较,PFOS染毒组和DAC干预组F1代仔鼠出生体重均较低,毛发长出时间均延长,差异有统计学意义(P<0.05,P<0.01);PFOS染毒组和SAM干预组、DAC干预组F1代仔鼠的开眼时间和自主采食出现时间均延长,差异有统计学意义(P<0.05),而耳廓伸展时间无明显改变。与PFOS染毒组比较,SAM干预组F1代仔鼠的出生体重较高,开眼时间和自主采食出现时间均缩短,差异有统计学意义(P<0.05,P<0.01);DAC干预组F1代仔鼠出生体重、耳廓伸展时间、毛发长出时间、开眼时间和自主采食出现时间均无明显改变。与对照组比较,PFOS染毒组和DAC干预组、SAM干预组F1代雄性大鼠睾丸生精细胞层次减少和生精上皮细胞排列松散的异常生精小管百分比均增加,差异均有统计学意义(P<0.05,P<0.01)。与PFOS染毒组比较,SAM干预组F1代雄性大鼠睾丸生精细胞层次减少和生精上皮细胞排列松散的异常生精小管百分比均下降,差异均有统计学意义(P<0.05);而DAC干预组以上2指标均无明显变化。F1代仔鼠正常饲养两个月后,PFOS染毒组有2雄4雌仔鼠;DAC干预组有3雄4雌仔鼠,其雌鼠均未受孕;而SAM干预组有4雄4雌仔鼠,雌鼠均受孕,但均因难产死亡。结论围产期PFOS慢性暴露能引起大鼠生长发育迟缓,生育力下降,并遗传子代,致子代不孕不育,这与损害雄性大鼠的睾丸组织结构和生殖功能有关。DAC可进一步加重PFOS引起的生殖发育毒性,而SAM可明显抑制PFOS暴露产生的生殖毒性作用。影响体内甲基化代谢可能是干预PFOS的生殖毒性作用的新途径。 Objective To investigate the effects of early low-dose exposure to perfluorooctane sulfonate (PFOS) on reproductive function and growth of rats and the effects of S-adenosyl-L methionine (SAM) and 5 Effect of decitabine (DAC) on it. Methods Forty Sprague-Dawley (SD) Sprague-Dawley (SD) SD rats of 5 days (PND5) were randomly divided into 4 groups (10 rats in each group) SAM intervention group and DAC intervention group. PFOS exposure group, SAM intervention group and DAC intervention group were exposed to 5 mg / kg PFOS respectively; SAM intervention group and DAC intervention group were given both 16 mg / kg SAM and 0.15 mg / kg DAC intervention; Department of subcutaneous injection of exposure, once a day, 28 d, once every 3 d, continued exposure to 60 d after birth (PND60). Daily observation of F0 generation of rats in general and determination of body weight. F0 generation of rats to be adult, the female and male rats by 1: 1 cages mating. When F1 generation rats were adult, 6 rats in each group were selected and caged in the ratio of 2: 1 for females and males, and the same method used to treat females during pregnancy and lactation (PND28). Observe the fertility of each generation of rats and offspring development, and observe the F1 generation of testicular tissue morphological changes. Results Compared with the control group, the PF0 group, the SAM intervention group and the DAC intervention group had lower conception rate and higher stillbirth rate and lower survival rate than the control group. In the PFOS group and DAC intervention group, The birth rate and postpartum mortality rate were higher, the differences were statistically significant (P <0.01, P <0.05). Compared with the PFOS-treated group, the pregnancy rate and survival rate of the F0 generation of female rats in the SAM intervention group were higher than those in the PFOS-treated group, with a low rate of stillbirth and teratogenicity. The death rate and survival rate of the F0 generation of female rats in the DAC- Postpartum mortality was higher, the difference was statistically significant (P <0.01, P <0.05). Compared with the control group, the PF10-exposed and DAC-treated F1 offspring had lower birth weight and longer hair growth time (P <0.05, P <0.01) In the SAM intervention group and the F1 intervention group, the opening times of the F1 generation and the time of self-feeding in the DAC intervention group were prolonged with statistical significance (P <0.05), while the auricle extension time did not change significantly. Compared with the PFOS group, the F1 generation offspring of SAM intervention group had higher birth weight, shorter opening time and shorter time of self-feeding, the difference was statistically significant (P <0.05, P <0.01); DAC intervention group F1 There was no significant change in birth weight, auricle extension time, hair growth time, open eye time and independent feeding time. Compared with the control group, the percentage of spermatogenic cells in testis and the percentage of abnormal seminiferous tubules in spermatogenic epithelial cells in PF intervention group and DAC intervention group and SAM intervention group were both increased, the differences were statistically significant (P <0.05, P <0.01). Compared with the PFOS-treated group, the percentage of spermatogenic cells in testis and the percentage of abnormal seminiferous tubules in spermatogenic epithelial cells were decreased in SAM-treated male rats (P <0.05) There was no significant change in the above two indexes in DAC intervention group. Two generations of F1 offspring were housed normally, and 2 male and 4 female offspring in the PFOS-treated group. There were 3 male and 4 female offspring in the DAC intervention group, Offspring, females are pregnant, but died of dystocia. Conclusion Perinatal chronic exposure to PFOS can cause slow growth and development of rats, fertility decline, and genetic offspring, offspring infertility, which is related to the damage to testicular tissue structure and reproductive function of male rats. DAC can further aggravate the reproductive and developmental toxicity caused by PFOS, while SAM can significantly inhibit the reproductive toxicity caused by PFOS exposure. Affecting methylation metabolism in vivo may be a new way to interfere with the reproductive toxicity of PFOS.