Related Experiment Video
Updated: May 29, 2026
Body Composition and Metabolic Caging Analysis in High Fat Fed Mice
Published on: May 24, 2018
SIRT6 in mouse spermatogenesis is modulated by diet-induced obesity
Nicole O Palmer1, Tod Fullston, Megan Mitchell
1Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia.
Abstract:
Male obesity is associated with reduced sperm function and increased incidence of sperm DNA damage; however, the underlying molecular mechanisms have not yet been identified. Mammalian SIRT6 protein is involved in caloric-dependant DNA damage repair in other tissue types, yet a possible role for SIRT6 in male obesity and subfertility has not been investigated previously. To assess SIRT6 levels and activity in the testes, male mice (n=12 per diet) were fed either a control diet (CD; 6% fat) or a high-fat diet (HFD; 21% fat) for 16 weeks before the collection of testes and spermatozoa. SIRT6 protein was localised to the nucleus of transitional spermatids and the acrosome of mature spermatozoa, with levels significantly decreased in HFD-fed male mice (P<0.05). This decrease in SIRT6 protein was associated with transitional spermatids having increased levels of acetylated H3K9 in the nucleus (P<0.01) and increased DNA damage (P<0.001). We propose a role for SIRT6 in spermiogenesis and potentially protamination processes, which are known to be compromised by male obesity.
Insights
Male obesity reduces SIRT6 protein in testes, leading to increased sperm DNA damage. This suggests SIRT6 plays a crucial role in male fertility, particularly during spermiogenesis.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Obesity Research
Background:
- Male obesity is linked to impaired sperm function and DNA damage.
- The molecular basis for obesity-induced male subfertility remains unclear.
- SIRT6 protein's role in male fertility and obesity has not been previously explored.
Purpose of the Study:
- To investigate the role of SIRT6 protein in the testes of male mice fed a high-fat diet.
- To determine if SIRT6 levels and activity are altered in obesity-associated male subfertility.
Main Methods:
- Male mice were fed either a control or high-fat diet for 16 weeks.
- Testes and spermatozoa were collected to assess SIRT6 protein levels.
- Sperm DNA damage and histone modifications (acetylated H3K9) were analyzed.
Main Results:
- High-fat diet significantly decreased SIRT6 protein levels in testes and spermatozoa.
- Reduced SIRT6 was correlated with increased nuclear acetylated H3K9 in spermatids.
- A significant increase in sperm DNA damage was observed in male mice on the high-fat diet.
Conclusions:
- SIRT6 protein is localized in spermatids and spermatozoa and is downregulated by high-fat diet-induced obesity.
- Decreased SIRT6 is associated with increased DNA damage during spermiogenesis.
- SIRT6 may be a key factor in obesity-related male subfertility, impacting spermiogenesis and protamination.