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目的探讨妊娠期邻苯二甲酸二丁酯(DBP)染毒对雌性子代大鼠生殖发育的影响。方法将50只健康SPF级SD妊娠大鼠按体重随机分为对照组和100、250、500、1 000 mg/kg DBP染毒组,每组10只。采用灌胃方式进行染毒,每天1次,从妊娠第12日至哺乳期第21日(postnatal day 21,PND21)结束。仔鼠出生4 d后,调整每窝仔鼠数量基本一致(12~13只),记录平均窝重,仔鼠出生存活率、仔鼠外观畸形率。断乳后,随机从每笼中抽取2只雌性仔鼠继续饲养至成年(PND63)。检测血清中孕酮和雌二醇的浓度及其合成相关酶[类固醇合成酶基因St AR(Star)、卵巢P450芳香化酶P450arom(Cyp19)、胆固醇侧链裂解酶P450 scc(Cyp11a1)、3β羟甾脱氢酶3βHSD1(Hsd3b1)、17β羟甾脱氢酶17βHSD1(Hsd17b1)、11β羟甾脱氢酶11βHSD1(Hsd11b1)]的m RNA表达水平。结果 1 000 mg/kg DBP染毒组仔鼠出生后不久变得苍白无力,很快便出现死亡现象,仔鼠出生当日存活率为50%(59/117),2 d内全部死亡。其余3个剂量DBP染毒组仔鼠未出现任何中毒症状和死亡现象。与对照相比较,250、500 mg/kg DBP染毒组仔鼠血清中孕酮和雌二醇的浓度较低,而100 mg/kg DBP染毒组仔鼠血清中雌二醇的浓度较高,差异均有统计学意义(P<0.05)。与对照组比较,各剂量DBP染毒组雌性仔鼠卵巢中star、cyp19、cyp11α、Hsd3b1、Hsd11b1 m RNA的表达水平均下降,差异均有统计学意义(P<0.05);而Hsd17b1 m RNA的表达水平均无明显改变。结论妊娠期DBP染毒对雌性仔鼠成年后的生殖系统有影响,其作用机制可能与雌激素合成相关酶基因表达的降低有关。
Objective To investigate the effects of dibutyl phthalate (DBP) on the reproductive development of female offspring in pregnancy. Methods Fifty healthy SPF SD pregnant rats were randomly divided into control group and 100, 250, 500 and 1000 mg / kg DBP exposure groups, with 10 rats in each group. Gavage was performed once daily, from the 12th day of gestation to the 21st day of postnatal day (PND21). After 4 days of birth, the number of littermates in each litter was adjusted to be basically the same (12-13). The average litter weight, birth survival rate of offspring, pupal deformity rate were adjusted. After weaning, 2 female offspring from each cage were randomized to continue feeding to adulthood (PND63). Serum concentrations of progesterone and estradiol and their synthetic enzymes [St AR (Star), ovary P450 aromatase P450 arom (Cyp19), cholesterol side chain cleaving enzyme P450 scc (Cyp11a1), 3 beta hydroxy Steroid dehydrogenase 3βHSD1 (Hsd3b1), 17β-hydroxysteroid dehydrogenase 17βHSD1 (Hsd17b1), 11β-hydroxysteroid dehydrogenase 11βHSD1 (Hsd11b1)]. Results The pups exposed to 1 000 mg / kg DBP became pale and weak soon after birth, and died soon after birth. The pups survived on the day of birth were 50% (59/117) and all died within 2 days. The remaining three doses of DBP exposure group did not show any toxic symptoms and death phenomenon. Compared with the control, serum concentrations of progesterone and estradiol were lower in the 250 and 500 mg / kg DBP exposure groups, while serum concentrations of estradiol in the DBP exposed 100 mg / kg group were higher , The differences were statistically significant (P <0.05). Compared with the control group, the expression levels of star, cyp19, cyp11α, Hsd3b1 and Hsd11b1mRNA in the ovaries of female offspring of DBP-exposed groups were significantly decreased (P <0.05), while those of Hsd17b1 m RNA No significant changes in expression levels. Conclusions DBP exposure during pregnancy affects reproductive system of adult female offspring. The possible mechanism may be related to the decrease of estrogen biosynthesis related gene expression.