Proteomic alterations underlie an association with teratozoospermia in obese mice sperm
Yuanhong Peng1, Wenzhen Zhao2,3, Fei Qu1
1Department of Histology, Embryology, Genetics and Developmental Biology, Shanghai Key Laboratory for Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Background:
Obesity is a worldwide crisis impairing human health. In this condition, declines in sperm quality stem from reductions in sperm concentration, motility and increase in sperm deformity. The mechanism underlying these alterations remains largely unknown. This study, determined if obesity-associated proteomic expression patterns in mice sperm parallel those in spermatozoa obtained from obese humans.
Methods:
An obese mouse model was established via feeding a high-fat diet (HFD). Histological analysis identified testicular morphology and a computer assisted semen analyzer (CASA) evaluated sperm parameters. Proteome analysis was performed using a label-free quantitative LC-MS/MS system. Western blot, immunohistochemical and immunofluorescent analyses characterized protein expression levels and localization in testis, sperm and clinical samples.
Results:
Bodyweight gains on the HFD induced hepatic steatosis. Declines in sperm motility accompanied sperm deformity development. Differential proteomic analysis identified reduced cytoskeletal proteins, centrosome and spindle pole associated protein 1 (CSPP1) and Centrin 1 (CETN1), in sperm from obese mice. In normal weight mice, both CSPP1 and CETN1 were localized in the spermatocytes and spermatids. Their expression was appreciable in the post-acrosomal region parallel to the microtubule tracks of the manchette structure in spermatids, which affects spermatid head shaping and morphological maintenance. Moreover, CSPP1 was localized in the head-tail coupling apparatus of the mature sperm, while CETN1 expression was delimited to the post-acrosomal region within the sperm head. Importantly, sperm CSPP1 and CETN1 abundance in both the overweight and obese males decreased in comparison with that in normal weight men.
Conclusion:
These findings show that regionally distinct expression and localization of CETN1 and CSPP1 is strongly related to spermiogenesis and sperm morphology maintaining. Obesity is associated with declines in the CETN1 and CSPP1 abundance and compromise of both sperm morphology in mice and relevant clinical samples. This parallelism between altered protein expression in mice and humans suggests that these effects may contribute to poor sperm quality including increased deformity.
Insights
Obesity negatively impacts sperm quality by reducing motility and increasing deformity. This study found obesity lowers levels of key proteins, centrosome and spindle pole associated protein 1 (CSPP1) and Centrin 1 (CETN1), in sperm, affecting morphology.
Area of Science:
- Reproductive biology
- Proteomics
- Obesity research
Background:
- Obesity is a global health issue linked to reduced sperm quality, including decreased concentration, motility, and increased deformity.
- The underlying mechanisms of obesity-induced sperm alterations are not fully understood.
- This study investigated if proteomic changes in mouse sperm due to obesity mirror those in human sperm.
Purpose of the Study:
- To determine if obesity-associated proteomic expression patterns in mouse sperm are comparable to those in human sperm.
- To identify specific proteins affected by obesity in sperm.
Main Methods:
- An obese mouse model was created using a high-fat diet (HFD).
- Sperm parameters were assessed using a computer-assisted semen analyzer (CASA).
- Proteomic analysis utilized label-free quantitative LC-MS/MS, with Western blot, immunohistochemical, and immunofluorescent analyses for protein validation.
Main Results:
- Obesity induced hepatic steatosis and decreased sperm motility and increased sperm deformity in mice.
- Proteomic analysis revealed reduced levels of cytoskeletal proteins, specifically centrosome and spindle pole associated protein 1 (CSPP1) and Centrin 1 (CETN1), in sperm from obese mice.
- Reduced CSPP1 and CETN1 abundance was also observed in sperm from overweight and obese human males compared to normal weight males.
Conclusions:
- Regionally distinct expression of CETN1 and CSPP1 is crucial for spermiogenesis and maintaining sperm morphology.
- Obesity is associated with decreased CETN1 and CSPP1 levels, leading to compromised sperm morphology in both mice and humans.
- The observed parallelism in protein alterations suggests a conserved mechanism contributing to obesity-related poor sperm quality.
