Effects of paternal pre-conceptional n-3 polyunsaturated fatty acids on telomere length in the offspring / 公共卫生与预防医学

ABSTRACT

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 liver and testes. Conclusion Maintaining paternal optimal n-3 PUFA status in pre-conception increases offspring TL, probably mediated by inheritance from increased TL in father and regulation on expressions of telomere transcriptase and binding proteins in the offspring, which may be helpful for promoting offspring development and disease prevention in adulthood.