宫内暴露氟他胺对子鼠子宫和卵巢发育及氧化应激的影响

doi:10.3969/j.issn.1004-616x.2018.05.011

癌变·畸变·突变 ›› 2018, Vol. 30 ›› Issue (5): 384-388,394.doi: 10.3969/j.issn.1004-616x.2018.05.011

宫内暴露氟他胺对子鼠子宫和卵巢发育及氧化应激的影响

周小青¹, 文可欣¹, 尹洪萍², 杨谨如¹, 朱勇飞¹

1. 湖南师范大学医学院, 湖南长沙 410013;
2. 杭州师范大学医学院, 浙江杭州 310018

收稿日期:2018-05-22 修回日期:2018-09-06 出版日期:2018-09-30 发布日期:2018-09-30
通讯作者: 朱勇飞,E-mail:njzhu70@163.com E-mail:njzhu70@163.com
作者简介:周小青,E-mail:517622847@qq.com。
基金资助:
湖南省教育厅重点项目（17A131）

Effects of intrauterine flutamide exposure on uterus and ovary development and on oxidative stress among female offspring

ZHOU Xiaoqing¹, WEN Kexin¹, YIN Hongping², YANG Jinru¹, ZHU Yongfei¹

1. School of Medicine, Hunan Normal University, Changsha 410013, Hunan;
2. School of Medicine, Hangzhou Normal University, Hangzhou 310018, Zhejiang, China

Received:2018-05-22 Revised:2018-09-06 Online:2018-09-30 Published:2018-09-30

摘要/Abstract

摘要： 目的：探讨氟他胺染毒孕鼠对子代雌鼠子宫、卵巢发育及其氧化应激的影响，为生殖系统畸形的发生机制研究提供线索。方法：8周龄自然受孕ICR雌性小鼠40只，设实验组和对照组，每组20只，实验组在孕12~18 d连续7 d进行300 mg/（kg·d）氟他胺灌胃，对照组以等体积大豆油灌胃。于子鼠出生7周后观察雌鼠外形，称体质量，取子宫、卵巢并称子宫、卵巢的质量，计算脏器指数。取小鼠子宫、卵巢组织制作切片，观察其病理学改变并对各级卵泡计数。而后每组随机检测12只子鼠子宫、卵巢中的超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）和丙二醛（MDA）的含量，并用实时荧光定量PCR（qPCR）方法检测子宫和卵巢中氧化应激基因Noxo1、Sod1及Gpx1的mRNA表达水平。结果：实验组雌性子鼠与对照组相比外观无明显差异，但体质量降低（P < 0.05），子宫与卵巢的脏器系数与对照组相比差异无统计学意义（P > 0.05）。卵泡计数结果显示，实验组原始卵泡数量和成熟卵泡数量比对照组少（P < 0.05）。实验组雌性子鼠子宫中SOD活性、GSH-Px含量低于对照组（P < 0.05），MDA含量高于对照组（P < 0.05）。实验组卵巢中SOD活性和GSH-Px含量低于对照组（P < 0.05），MDA含量与对照组间的差异无统计学意义（P > 0.05）。实验组子宫中Noxo1mRNA表达水平升高，Sod1 mRNA的表达水平降低，Gpx1 mRNA的表达水平与对照组相比差异无统计学意义（P > 0.05）。实验组卵巢中Noxo1 mRNA表达水平升高、Gpx1 mRNA的表达水平降低（P < 0.05），Sod1 mRNA的表达水平与对照组间差异无统计学意义（P > 0.05）。结论：氟他胺染毒孕鼠可致子代雌鼠子宫和卵巢发育异常，并抑制其子宫和卵巢的抗氧化应激能力。

关键词: 氟他胺, 子鼠, 子宫, 卵巢, 氧化应激

Abstract: OBJECTIVE:To investigate the effects of flutamide exposure in pregnant mice on their uterus and ovarian development,and on oxidative stress among offspring,and to provide mechanistic understanding of reproductive system malformation. METHODS:40 eight-week-old conceived ICR females mice were randomly assigned into treatment and the control groups. Flutamide was orally administered to pregnant mice at 300 mg/(kg·d) during gestation days 12-18,while the control group was treated with equal volume of soybean oil. More than 7 weeks after birth,the appearance of female offspring was observed. The body weights, uterine weight, ovarian weight were collected to calculate the organ coefficient. The uterus and ovarian tissues were taken for sectioning,and the pathological changes were observed. Follicles of each level were counted and their pathological changes observed. Then 12 animals were randomly taken out for measuring the superoxide dismutase (SOD),glutathioneperoxidase (GSH-Px) and malonaldehyde (MDA) of the uterus and ovary in each dose group,and their abundance of Nox1,Sod1 and Gpx1 was detected by qPCR. RESULTS:Compared to the control group,there was no significant difference in the appearance of the female offspring in the treatment group,but the body weight was lower than control(P < 0.05),the visceral coefficients of uterus and ovary had no statistical difference from the control group(P > 0.05). The results of follicle count showed that the numbers of primordial follicles and mature follicles in the experimental group were less than control(P < 0.05). The SOD activity and GSH-Px level in the uterus of the treatment female mice were lower than those in the control group,and the MDA level was higher(P < 0.05). In the ovary of the treatment group,the SOD activity and GSH-Px level were lower(P < 0.05),and the MDA level had no significantly difference(P > 0.05). The mRNA abundance of Noxo1 in the uterus of the experimental group was increased,while the abundance of Sod1 mRNA was decreased (P < 0.05),and the abundance of Gpx1 mRNA was not statistically different from the control(P > 0.05). The mRNA abundance of Noxo1 was increased and the abundance of Gpx1 in the ovary of the treatment group were decreased (P < 0.05),and the mRNA abundance of Sod1 has no statistically difference from the control group(P > 0.05). CONCLUSION:Data from our study show that pregnant mice exposed to flutamide caused abnormal uterus and ovarian development in their offspring and demonstrated anti-oxidative stress.

Key words: flutamide, female offspring, uterus, ovary, oxidative stress

中图分类号:

R994.6

周小青, 文可欣, 尹洪萍, 杨谨如, 朱勇飞. 宫内暴露氟他胺对子鼠子宫和卵巢发育及氧化应激的影响[J]. 癌变·畸变·突变, 2018, 30(5): 384-388,394.

ZHOU Xiaoqing, WEN Kexin, YIN Hongping, YANG Jinru, ZHU Yongfei. Effects of intrauterine flutamide exposure on uterus and ovary development and on oxidative stress among female offspring[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2018, 30(5): 384-388,394.

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宫内暴露氟他胺对子鼠子宫和卵巢发育及氧化应激的影响

Effects of intrauterine flutamide exposure on uterus and ovary development and on oxidative stress among female offspring

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