Study Title and Description
The effects of male age on sperm DNA damage in healthy non-smokers.
Key Questions Addressed
|1||For [population], is caffeine intake above [exposure dose], compared to intakes [exposure dose] or less, associated with adverse effects on reproductive and developmental outcomes?|
Primary Publication Information
|Title||The effects of male age on sperm DNA damage in healthy non-smokers.|
|Author||TE Schmid,B Eskenazi,A Baumgartner,F Marchetti,S Young,R Weldon,D Anderson,AJ Wyrobek,|
Secondary Publication Information
There are currently no secondary publications defined for this study.
Extraction Form: Reproductive Toxicity - Design Details
No arms have been defined in this extraction form.
|Question... Follow Up||Answer||Follow-up Answer|
|What outcome is being evaluated in this paper?||Reproductive and Development|
|What is the objective of the study (as reported by the authors)?||The purpose of our study was to (i) investigate the association between male age and DNA damage in sperm within a group of generally healthy non-smokers, using sperm Comet analyses performed under both alkaline and neutral conditions to detect alkali-labile sites, single- and double-stranded DNA breaks (Haines et al ., 1998; Hughes et al ., 1999; Morris et al ., 2002) and (ii) characterize associations between sperm Comet results and previously reported data on conventional semen quality and sperm DNA fragmentation as measured by SCSA for the same group of men (Eskenazi et al ., 2003; Wyrobek et al ., 2006). Additionally, we investigated the influence of several common lifestyle factors on sperm DNA damage using questionnaire data|
|Provide a general description of the methods as reported by the authors. Information should be extracted based on relevance to the SR (i.e., caffeine related methods)||Methods Study Population: 80 healthy male volunteers, aged 22-80 (AGES study); 20 were excluded and 18 refused to participate. Men were mailed a semen collection container with instructions and a questionnaire on medical and reproductive history, sociodemographic characteristics (age, race and education), occupation, possible exposures, diet and lifestyle habits. Semen samples were analyzed for count and motility upon collection and immediately stored at −80°∆C. Sperm comet analyses Each specimen was analysed under both alkaline and neutral conditions. Fifty cells were scored from each of the two replicate slides for each specimen (100 cells in total); percentage tail DNA (% tail DNA, the average percentage of DNA staining outside the area of the sperm nucleus in the electrophoresis) was analyzed (limited to % tail DNA). Statistical analyses: Age was examined as a categorical variable, by decade, and as a continuous variable. Differences in % tail DNA among covariates were examined using analysis of variance (ANOVA) and t-tests. The trends by age decade were calculated by a non-parametric test across the ordered groups (Cuzick, 1985), and the correlations were determined using Pearson’s correlation. The following variables were evaluated as potential covariates: time from sample collection to sample processing; duration of sexual abstinence before semen collection; season of sample collection; exposure to occupational chemicals and radiation; history of working with radioisotopes; history of tobacco use; alcohol and caffeine intake; prescription and non-prescription medication use; history of chronic disease such as high blood pressure, heart problems or diabetes; history of genitourinary disease including urinary tract or other genitourinary infection, sexually transmitted diseases or history of infertility; fatherhood history; BMI; ethnicity; diet characteristics and vitamin supplement use. Covariates were included if: (i) they were related to Comet parameters or age in univariate analyses (P < 0.2) and (ii) they changed the parameter estimate of age by at least 10% or they were statistically significant (P < 0.1) in controlled bivariate models. Once the full models were built, covariates were again evaluated using a stepwise backward elimination process and retained for the final model if they changed the parameter estimate of age by at least 10% or if they were statistically significant (P < 0.1). Relationships between sperm Comet and conventional semen quality and SCSA outcomes were determined using Pearson’s correlations and multiple linear regressions. Age and duration of abstinence were examined as potential covariates.|
|How many outcome-specific endpoints are evaluated?||1|
|What is the (or one of the) endpoint(s) evaluated? (Each endpoint listed separately)||DNA damage in sperm (via Comet assay)|
|List additional health endpoints (separately).|
|List additional health endpoints (separately)|
|What is the study design?||Cohort|
|Randomized or Non-Randomized?|
|What were the diagnostics or methods used to measure the outcome?||Objective|
|Optional: Name of Method or short description||Comet assay|
|Caffeine (general)||Caffeine (general)|
|What was the reference, comparison, or control group(s)? (e.g. high vs low consumption, number of cups, etc.)||caffeine intake (not clarified by authors, based on text from results, analyses appear to be based on cups of coffee evaluated continuously and by tertiles)|
|What were the listed confounders or modifying factors as stated by the authors? (e.g. multi-variable components of models. Copy from methods)||The following variables were evaluated as potential covariates: time from sample collection to sample processing; duration of sexual abstinence before semen collection; season of sample collection; exposure to occupational chemicals and radiation; history of working with radioisotopes; history of tobacco use; alcohol and caffeine intake; prescription and non-prescription medication use; history of chronic disease such as high blood pressure, heart problems or diabetes; history of genitourinary disease including urinary tract or other genitourinary infection, sexually transmitted diseases or history of infertility; fatherhood history; BMI; ethnicity; diet characteristics and vitamin supplement use|
|Provide a general description of results (as reported by the authors).||Higher caffeine intake was associated with higher values of neutral % tail DNA (P < 0.1, unadjusted), but not alkaline % tail DNA. Men were then assigned to tertiles based on caffeine consumption, and men with >308 mg of caffeine intake per day (equivalent to ∼ 2.9 cups of coffee) had ∼ 20% higher neutral % tail DNA than men with no caffeine intake (P = 0.01 unadjusted; P = 0.005 after adjusting for the covariates total kilocalorie intake and the history of urinary tract infections).|
|Did the authors perform a dose-response analysis (or trend/related analysis)?||Yes|
|What were the authors's observations re: trend analysis?||Higher caffeine intake was associated with higher values of neutral % tail DNA (P < 0.1, unadjusted), but not alkaline % tail DNA|
|What were the author's conclusions?||We also found that men with high caffeine consumption (∼3 cups per day or more) had significantly higher frequencies of sperm with DNA damage as measured under neutral, but not alkaline conditions compared to men with less caffeine consumption. Our finding that higher daily caffeine intake is associated with increased frequencies of damaged sperm, suggests the need for future studies to investigate the roles of dietary factors on sperm DNA damage in ageing males.|
|What were the sources of funding?||This work was performed in part under the auspices of the US Department of Energy by Lawrence Livermore National Laboratory, contract W-7405-ENG-48, with funding from NIEHS Superfund P42ES04705. A.B. was a Marie Curie fellow, EC Contract No: QLG4-CT-2002-51611.|
|What conflicts of interest were reported?||Not addressed by authors.|
|Does the exposure (dose) need to be standardized to the SR?||No|
|Provide calculations/conversions for the exposure based on the decision tree in the guide (for all endpoints/exposure levels of interest).|
|List all the endpoint(s) followed by the dose (mg) which will be used in comparison to Nawrot. Characterize value as LOAEL/NOAEL, etc. if possible.||LOEL = >308 mg/day for frequency of DNA damage in sperm|
|Notes regarding selection/listing of endpoints and exposures/doses to be compared to Nawrot.||Some difficulty in determining when significance was achieved (and which covariates were included to achieve significance)|
|What is the importance of the study with respect to the adverseness of the outcome?||Important|
No baseline characteristics have been defined for this extraction form.
Results & Comparisons
No Results found.
|Arm or Total||Title||Description||Comments|
No quality dimensions were specified.
No quality rating data was found.