Dietary selenium excess affected spermatogenesis via DNA damage and telomere-related cell senescence and apoptosis in mice

Selenium (Se) is a vital microelement for spermatogenesis and male fertility. The aim of this study was to investigate the effects of Se on the male reproductive function and possible mechanisms. Fourty male mice were randomly divided into 0, 0.1, 0.3 and 0.9 mg/kg Se supplementation groups and given with Se dietary inter-vention for 12 weeks. Our data showed that excessive Se intake damaged the tissue structure of testes and epididymides of the mice, resulting in decreased sperm quality and quantity. Moreover, excessive Se induced oxidative stress, causing DNA damage and activated DNA damage repair factors (Mre11/Rad50/Nbs1), and also disrupted telomere function by shortening telomere length and decreasing TERT expression. Se excess activated the senescence pathway p53/p21/p16, leading to germ cell senescence, and inhibited cell proliferation by suppressing the Sirt1/Foxo1/c-Myc pathway. All of this led to spermatogenic cell apoptosis, thereby causing a decrease of sperm quantity and quality. In conclusion, excessive Se caused reproductive toxicity via inducing telomere dysfunction due to DNA damage, leading to germ cellular senescence and apoptosis in the testes of male mice. Our research provide new proof to explain the underlying mechanism of male reproductive toxicity trig-gered by excessive Se intake.

Automated summary

The study aimed to investigate the effects of selenium on male reproductive function and its possible mechanisms. Excessive selenium intake damaged the tissue structure of the testes and epididymides of mice, resulting in decreased sperm quality and quantity. Furthermore, excessive selenium induced oxidative stress, DNA damage, and disrupted telomere function. These effects led to germ cell senescence and apoptosis in the testes.