摘要
目的探讨父代备孕期n-3多不饱和脂肪酸(n-3 PUFAs)对子代端粒长度(TL)的影响。方法将3~4周龄C57BL/6J雄性小鼠(父代)随机分为3组(10只/组),分别给予n-3 PUFAs缺乏(n-3 D)、n-3 PUFAs正常含量(n-3 N)和n-3 PUFAs高含量(n-3 H)饲料饲喂12周,然后与12周龄正常体重的同品系雌性小鼠交配繁育子代小鼠。对成年期子代小鼠进行外周血和组织TL以及端粒酶和端粒结合蛋白基因mRNA表达检测。结果与n-3 N饲料相比,父代n-3 D饲料喂养使得子代雌和雄性小鼠的外周血、肝脏、脂肪组织和/或脑组织中的TL显著缩短,伴随雄性肝脏端粒酶组分TERC以及结合蛋白TRF2和POT1a的mRNA表达下调;同时显著缩短了子代睾丸TL并下调了端粒酶(TERT)和结合蛋白(TRF1、TRF2、POT1a)的mRNA表达。父代n-3 H饲料喂养虽然未改变子代的TL和肝脏端粒酶及结合蛋白表达,但却显著逆转了n-3 D饲料的不良影响。另外,相对于n-3 N饲料,父代n-3 D和n-3 H饲料喂养均未改变自身睾丸TL,但n-3 H饲料喂养时睾丸TL以及端粒结合蛋白TRF1、TRF2、POT1a和RAP1的表达显著高于n-3 D饲料喂养。结论父代备孕期良好的n-3 PUFAs营养状态可能通过父代生殖细胞中TL的遗传以及对子代端粒酶和端粒结合蛋白表达的调控增加子代小鼠的TL,这可能有助于促进子代发育以及成年后相关慢病的预防。
Objective To investigate the effects of paternal pre-conceptional n-3 polyunsaturated fatty acids(n-3 PUFAs)on telomere length(TL)in the offspring.Methods Three to four-week old male C57 BL/6J mice(Father)were randomly divided into three groups and fed either an n-3 PUFA-deficient(n-3 D)(n-6∶n-3 PUFA ratio=47.2∶1)diet,a diet with normal n-3 PUFA content(n-3 N)(n-6∶n-3 PUFA ratio=4.3∶1),or a diet with high n-3 PUFA content(n-3 H)(n-6∶n-3 ratio=1.5∶1),for 12 weeks.Then,the offspring were generated by mating the father mice with 12-week-old virgin female C57 BL/6J mice.The TL,mRNA expression of telomere transcriptase and binding proteins,as well as DNA methylation in the TERT promoter region were determined in adult offspring mice.Results Compared to n-3 N diet,paternal feeding with n-3 D diet during preconception decreased offspring TL in the peripheral blood cells,liver,adipose tissue and brain,accompanied by upregulated hepatic mRNA expression of TIN2 in the female,and downregulated hepatic expression of TERC,and binding proteins TRF2 and POT1a in the male.Meanwhile,paternal n-3 D diet shortened testis TL in offspring instead of themselves,with altered mRNA expression of TERT and binding proteins TRF1,TRF2 and POT1a.Paternal n-3 H diet showed no differences in effects on offspring TL and expressions of TERC and binding proteins with n-3 N diet,but normalized the alterations in associated parameters resulted from paternal n-3 D diet.In addition,although paternal n-3 D or n-3 H diet did not affect testis TL in themselves compared to n-3 N diet,fathers fed n-3 H diet had longer testis TL and higher expression of TRF1,TRF2,POT1a and RAP1 than those fed n-3 D diet.Finally,the DNA methylation fraction in the TERT promoter in offspring testes and male offspring liver was no difference between paternal n-3 D and n-3 N diet groups.CpG sites with altered methylation were less(1 site)between paternal n-3 H and n-3 N diet groups than those(5 sites)between paternal n-3 H and n-3 D diet groups in male offspring liv
作者
石巧玉
齐可民
SHI Qiaoyu;QI Kemin(Laboratory of Nutrition and Development,Key Laboratory of Major Diseases in Children,Ministry of Education,Beijing Pediatric Research Institute,Beijing Children′s Hospital,Capital Medical University,National Center for Children′s Health,Beijing 100045,China)
出处
《公共卫生与预防医学》
2024年第1期1-6,共6页
Journal of Public Health and Preventive Medicine
基金
北京市医疗卫生改革与发展研究专项(bjsekyjs-2023营养与发育)。
关键词
父代营养
子代
端粒长度
N-3多不饱和脂肪酸
Paternal nutrition
Offspring
Telomere length
N-3 polyunsaturated fatty acids
