大豆异黄酮和双酚A联合暴露对雌性大鼠不同组织雌激素受体表达的影响

Effects of Lactational Exposure to Combination of Soy Isoflavones and Bisphenol A on Estrogen Receptors in Neonate Female Rats

目的研究大豆异黄酮和双酚A哺乳期联合暴露对SD雌性大鼠的子宫增生效应及其对下丘脑-垂体-卵巢轴雌激素受体(ERα和ERβ)表达的影响。方法将母鼠及其仔鼠随机分至4组,即阴性对照组、大豆异黄酮组(每公斤体重150mg,i.g.)、双酚A组(每公斤体重150mg,i.g.)、联合暴露组(每公斤体重150mg大豆异黄酮+每公斤体重150mg双酚A,i.g.)。母鼠在产后第5至11天给予受试物,仔鼠在出生后5至11d(PND5-PND11)通过母乳暴露受试物。在PND12处死部分雌性仔鼠。剩余雌性仔鼠观察阴门开口时间和动情周期,并于PND70处死。剥离子宫并称重,病理学检查;利用Westernblot方法测定下丘脑、垂体、卵巢和子宫的ERα和ERβ表达。结果与阴性对照组比较,PND12时,大豆异黄酮组和双酚A组大鼠子宫体重比显著增加(P<0.05),联合暴露组子宫体重比亦显著增加(P<0.05),但其幅度略低于大豆异黄酮组和双酚A组。PND70时,各组大鼠的子宫体重比差异无统计学意义(P>0.05)。大豆异黄酮组、双酚A组和联合暴露组的阴门开口时间和动情周期与对照组比较差异无统计学意义(P>0.05)。在PND12和PND70时,大豆异黄酮组、双酚A组和联合暴露组大鼠下丘脑、垂体、卵巢和子宫的ERα和ERβ表达有部分增强或减弱。结论哺乳期大鼠大豆异黄酮和双酚A联合暴露时,可促进雌性仔鼠的子宫发育,但两者并未表现出协同作用;这种子宫增生效应在生命后期消失。大豆异黄酮和双酚A的子宫效应可能与对下丘脑-垂体-卵巢轴和子宫组织中ERα和ERβ表达的调节有关。

Objective To investigate the uterotrophic effects of lactational exposure to combination of soy isoflavones （SIF） and bisphenol A （BPA） and its potential mechanisms involved with estrogen receptor expressions in neonate female rats. Method Maternal rats, breeding about 8 litters, were randomly divided into four groups with seven dams in each group. Dams in different treatment groups received corn oil （control）, 150 mg/kg BW of SIF, 150 mg/kg BW of BPA or 150 mg/kg BW of SIF plus 150 mg/kg BW of BPA, respectively, from postnatal day 5 to 11 （PNDS-11） by gavage. On PND12 and PND70, 10 female litters were killed and uteri were removed for pathological evaluation after weighing. And vaginal opening time （VO） and estrus cycle （EC） were examined in animals fed for PND70. Expressions of estrogen receptor α （ERα） and Estrogen receptor β （ERβ） in hypothalamus, pituitary, ovary and uterus were examined using Western blotting assay. Results On PND12, The ratios of uterine weight to body weight in rats treated with ISF and BPA alone or combination increased significantly than those in the control group （ P 〈 0.05）. And this ratio in combination exposure group was slightly lower than those in individual exposure groups. On PND 70, however, ratios of uterus to body weight in each treatment group were no statistically different from that in the control group （ P 〉 0.05）. VO and EC in ISF and BPA alone or combination treatment groups were similar to that in control group （ P 〉 0.05）. Additionally, ERα and ERβ expression were up-regulated or down-regulated in hypothalamus, pituitary, ovary and uterus from female rats treated with ISF and BPA alone or combination on PND12 and even on PND70. Conclusion Lactational exposure to combination of SIF and BPA could induce uterotrophic response, which disappeared in later life, in neonate rats. The data didn＇t suggest a potential for synergy between SIF and BPA. It was also demonstrated that the uterotrophic effect might, at least, involve with modification of ERα and ERβ expressions in hypothalamus-pituitary-ovary axis after SIF and BPA exposure.