砷致雌性大鼠生殖系统损害的研究

Reproductive Damage in Female Rats Exposed to Arsenic

  • 摘要:
    目的 探讨砷致雌性大鼠生殖系统的损害作用。
    方 法 以雌性SD大鼠为实验动物,随机分成4组,每组6只,亚砷酸钠(NaAsO2)染毒剂量:对照组(0 mg/kg)、低砷组(0.36 mg/kg)、中砷组(1.44 mg/kg)、高砷组(5.77 mg/kg),连续灌胃染毒3个月,实验结束后检测大鼠尿砷(UAs)、卵巢砷(OAs)及大鼠血清中雌激素受体(ER)、孕激素受体(PR)、血管内皮生长因子(VEGF)、细胞周期素D1(CYC-D1)蛋白表达水平,并观察卵巢病理学改变。
    结果 (1)各砷染毒组ER、PR、VEGF、CYC-D1均明显低于对照组(P<0.01),且随着砷染毒剂量的增高,表达水平逐渐降低。(2)UAs、OAs与ER、PR、VEGF、CYC-D1均呈负相关(P<0.05),ER与PR、VEGF、CYC-D1间均呈正相关(P<0.05)。(3)光镜下,中砷、高砷组大鼠卵巢HE染色可见卵泡闭锁或塌陷,间质细胞大量增生呈铺石板状或梭状排列。
    结论 ER-PR/VEGF/CYC-D1信号通路可能参与砷暴露致雌性大鼠的生殖损害,卵泡的减少、闭锁及间质细胞过度增生可能是砷中毒对大鼠卵巢损害的主要病理类型。

     

    Abstract:
    Objective  To examine the reproductive damage induced by arsenic in female rats.
    Method  Female SD rats were randomly assigned into four groups with six rats each and exposed to sodium arsenite (NaAsO2) (0, 0.36, 1.44, and 5.77 mg/kg for control and low, middle, and high dose arsenic groups) by oral perfusion for three months. Urinary arsenic (UAs), ovary arsenic (OAs), and serum estrogen receptor (ER), progesterone receptor (PR), vascular endothelial growth factor (VEGF), and cyclin D1 (CYC-D1) protein expression levels were determined. The pathological changes of ovary were also observed.
    Result  (1) ER, PR, VEGF, and CYC-D1 were lower in the exposed groups than those in the control group (P<0.01) and decreased with higher doses of arsenic. (2) UAs and OAs were negatively associated with ER, PR, VEGF, and CYC-D1 (P<0.05); ER was positively associated with PR, VEGF, and CYC-D1 (P<0.05). (3) Under HE staining and light microscope, follicular atresia and collapse were observed in the ovary of rats treated with middle or high dose arsenic, and large amounts of stromal cells were arranged in a stone-like or spindle-like form.
    Conclusion  ER-PR/VEGF/CYC-D1 pathways may participate in the reproductive damage caused by arsenic exposure. Follicular atresia and collapse and stromal cell hyperplasia are major pathological changes.

     

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