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Ascorbic acid protects against endogenous oxidative DNA damage in human sperm
C G Fraga1, P A Motchnik, M K Shigenaga
1Division of Biochemistry and Molecular Biology, University of California, Berkeley 94720.
Abstract:
Damage to the DNA of germ cells can lead to mutation, which may result in birth defects, genetic diseases, and cancer. The very high endogenous rate of oxidative DNA damage and the importance of dietary ascorbic acid (AA) in preventing this damage has prompted an examination of these factors in human sperm DNA. The oxidized nucleoside 8-hydroxy-2'-deoxyguanosine (8-oxo-7,8-dihydro-2'-deoxyguanosine; oxo8dG), 1 of approximately 20 major products of oxidative damage to DNA, was measured in DNA isolated from human sperm provided by healthy subjects and compared to the seminal fluid AA levels. This relationship was studied in two groups. In a group of 24 free-living individuals 20-50 years old high levels of oxo8dG were correlated with low seminal plasma AA. The endogenous level of oxo8dG in this group was 13 fmol per microgram of DNA or approximately 25,000 adducts per sperm cell. The second group of individuals was maintained on a controlled diet that varied only in AA content. When dietary AA was decreased from 250 to 5 mg/day, the seminal fluid AA decreased by half and the level of oxo8dG in sperm DNA increased 91%. Repletion of dietary AA for 28 days (from 5 mg/day to 250 or 60 mg/day) caused a doubling in seminal fluid AA and reduced oxo8dG by 36%. These results indicate that dietary AA protects human sperm from endogenous oxidative DNA damage that could affect sperm quality and increase risk of genetic defects, particularly in populations with low AA such as smokers.
Insights
Dietary ascorbic acid (AA) protects human sperm DNA from oxidative damage. Low AA levels correlate with increased DNA damage, highlighting AA's role in preventing genetic defects and maintaining sperm quality.
Area of Science:
- Reproductive biology
- Nutritional science
- Genetics
Background:
- Germ cell DNA damage can cause mutations, leading to birth defects, genetic diseases, and cancer.
- Oxidative DNA damage is a significant concern, and dietary ascorbic acid (AA) plays a crucial role in its prevention.
- Understanding the relationship between oxidative DNA damage and AA in human sperm is vital for reproductive health.
Purpose of the Study:
- To investigate the correlation between seminal fluid ascorbic acid (AA) levels and oxidative DNA damage in human sperm.
- To determine the impact of dietary AA intake on the levels of 8-hydroxy-2'-deoxyguanosine (oxo8dG), a marker of oxidative DNA damage, in sperm DNA.
Main Methods:
- Measurement of 8-hydroxy-2'-deoxyguanosine (oxo8dG) in human sperm DNA from healthy subjects.
- Comparison of oxo8dG levels with seminal fluid AA concentrations in two groups of individuals.
- Controlled dietary manipulation of AA intake (ranging from 5 to 250 mg/day) to assess its effect on sperm DNA damage.
Main Results:
- A significant inverse correlation was observed between seminal plasma AA levels and oxo8dG in sperm DNA among free-living individuals.
- In a controlled study, decreasing dietary AA led to a 91% increase in sperm DNA oxo8dG.
- Increasing dietary AA repletion for 28 days significantly reduced oxo8dG levels in sperm DNA by 36%.
Conclusions:
- Dietary ascorbic acid (AA) effectively protects human sperm DNA from endogenous oxidative damage.
- Maintaining adequate AA levels is crucial for preserving sperm quality and reducing the risk of genetic defects.
- Populations with low AA intake, such as smokers, may be particularly vulnerable to increased oxidative DNA damage in sperm.