肥胖母鼠对雄性子代生殖力的影响及其机制研究  

Effects of obese female mice on fertility of male offspring and its mechanism

作　　者：尹睿 岳小枫 谭小音 李练兵 卢大儒 YIN Rui;YUE Xiaofeng;TAN Xiaoyin;LI Lianbing;LU Daru(Reproductive Medicine Research Center,Medical Research Institute,Southwest University,Chongqing 400715;Key Laboratory of Birth Defects and Reproductive Health of National Health Commission,Chongqing Population and Family Planning Science and Technology Research Institute,Chongqing 400020;School of Life Sciences,Fudan University,Shanghai 200438;Department of Urology,The Third Affiliated Hospital of Chongqing Medical University,Chongqing 401120,China)

机构地区：[1]西南大学医学研究院生殖医学研究中心,重庆400715 [2]重庆市人口和计划生育科学技术研究院/国家卫生健康委出生缺陷与生殖健康重点实验室,重庆400020 [3]复旦大学生命科学学院,上海200438 [4]重庆医科大学附属第三医院泌尿外科,重庆401120

出　　处：《癌变．畸变．突变》2023年第2期109-115,共7页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：重庆市自然科学基金重点项目(cstc20220jcyj-zdxmX0011);重庆市自然科学基金博士后基金(cstc2020jcyj-bsh0238);重庆市科研机构绩效激励引导专项项目(cstc2021jxjl130017)。

摘　　要：目的:探讨母体肥胖小鼠对雄性子代生殖能力的影响及其可能机制。方法:以高脂饮食诱导8周建立雌性小鼠肥胖模型,分别与正常饮食雄性小鼠合笼,子鼠出生后分为母体肥胖组和正常对照组,断奶后正常饮食喂至8周,每组随机选取8只雄性子鼠麻醉后处死,分离睾丸和附睾组织,检测精子质量,ELISA法检测睾丸性激素水平,免疫荧光法检测睾丸活性氧(ROS)水平,qPCR和Western blot法分别检测FOXO1、Nrf2基因的mRNA和蛋白表达水平。结果:与对照组相比,母体肥胖组小鼠精子浓度、精子活力和前向运动精子比率均显著降低(P<0.01),精子畸形率显著升高(P<0.01)。其他检测结果显示,母体肥胖能引起子代睾丸组织损伤,睾丸内性激素分泌紊乱,睾丸组织ROS水平升高,精原细胞标志物FOXO1表达水平显著上升,氧化应激水平和Nrf2蛋白表达水平均升高(均为P<0.01)。结论:在母体肥胖的情况下,子代雄性小鼠睾丸组织存在氧化应激,可能导致精原细胞分化障碍,引起子代生殖损伤。OBJECTIVE:To investigate effects of obese female mice on reproductive ability of male offspring and their possible mechanisms.METHODS:A female mouse obesity model was established by high-fat diet induction for 8 weeks,and caged with normal diet male mice.After birth,the offspring were divided into maternal obesity group and normal control group and fed with normal diet until 8 weeks after weaning.From each group of mice,8 male offspring were randomly selected and executed after anesthesia.From them,testes and epididymis tissues were isolated,sperm quality was evaluated,testicular sex hormone levels were detected by ELISA,testes were analyzed using by immunofluorescence Expression levels of mRNA and protein for FOXO1 and Nrf2 genes were detected by qPCR and Western blot,respectively.RESULTS:Compared with the control group,sperm concentrations,sperm motilities and forward motion sperm ratios were significantly lower(P<0.01)and the sperm malformation rates were significantly higher(P<0.01)in the maternal obese mice.Other test results showed that maternal obesity could cause testicular tissue damage in the offspring,disturbance in testicular endocrine hormone secretion,elevated testicular tissue ROS levels,significantly increased expression levels of the spermatogonial marker FOXO1,and elevated oxidative stress levels and Nrf2 protein expressions(all P<0.01).CONCLUSION:Due to maternal obesity,oxidative stress levels were elevated in testicular tissues of offspring male mice which might have caused impaired their spermatogonial differentiation and reproductive capacity.

关 键 词：母体肥胖 雄性子代 精原细胞 精子发生 叉头转录家族O1 

分 类 号：R589.2[医药卫生—内分泌]