No association between body mass index and sperm DNA integrity.

STUDY QUESTION: Is overweight associated with impaired sperm DNA integrity? SUMMARY ANSWER: High body mass index (BMI) is not associated with impaired sperm DNA integrity as assessed by the DNA Fragmentation Index (DFI). WHAT IS KNOWN ALREADY: Previous studies, based on fewer subjects and including mainly subfertile men, have shown conflicting results regarding the influence of overweight and obesity on sperm DNA integrity. STUDY DESIGN, SIZE, DURATION: This cross-sectional study was based on semen samples from 1503 men from the general population. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included two cohorts (cohort A and B) of military recruits (n = 275, n = 304, respectively), one group (cohort C) of fertile men and men without known fertility problems (n = 724), and one group (cohort D) of men between 19 and 40 years without known fertility problems (n = 200). In all cohorts, data were available on BMI, DFI as measured by the sperm chromatin structure assay (SCSA), standard semen characteristics, and potential confounders (age, abstinence time, smoking habits). The subjects were categorized according to BMI into four groups: underweight (<18.5 kg/m(2)), normal weight (18.5-24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)) and obese (≥30.0 kg/m(2)). Using a linear regression model, the inter-group differences in DFI were calculated. Furthermore with the normal-weight group as the reference, the odds ratios (ORs) for DFI > 20% and DFI > 30%, were calculated for the other groups. Calculations were made for the material as a whole and after exclusion of cohort C which included proven fertile men. MAIN RESULTS AND THE ROLE OF CHANCE: We found that normal-weight men had significantly higher DFI than overweight men, with a mean difference of 1.13% (95% CI: 1.05-1.22%); P = 0.001). Overweight men had a reduced risk of having DFI ≥ 20% and DFI ≥ 30%, compared with normal-weight men; adjusted odds ratio (OR) = 0.61 (95% CI: 0.42-0.88; P < 0.01) and adjusted OR = 0.48 (95% CI: 0.28-0.84; P < 0.01), respectively. When excluding cohort C, the statistical significance was lost. Regarding standard semen parameters, we found that obese men had a higher percentage of progressive motile spermatozoa than normal-weight men; mean difference 1.15% (95% CI: 1.02-1.30%, P < 0.05) but the significance was lost when excluding cohort C. All other standard semen parameters were unaffected by BMI. LIMITATIONS, REASONS FOR CAUTION: A main limitation might be the cross-sectional nature of the data. Furthermore our study included a significant proportion of men with proven fertility (75% of cohort C, n = 550), and could therefore be biased toward fertility. WIDER IMPLICATIONS OF THE FINDINGS: Our study indicates that overweight per se is not associated with a higher level of sperm DNA damage. STUDY FUNDING/COMPETING INTERESTS: This research has been given grants from the following: EU 5th and 7th framework program (Inuendo and Clear projects, [Contracts no. QLK4-CT-2001-00202 and FP7-ENV-2008-1-226217)]), the Swedish Research Council (Grants No. 2007-2590, 521-2004-6072 and 521-2002-3907); the Swedish Governmental Funding for Clinical Research, Skåne county council's research and development foundation, MAS Funds, University Hospital MAS Foundation in Malmö, Crafoordska Fund, Ove Tulefjords Fund, Foundation for Urological Research, Fundacion Federico SA, and Gunnar Nilssons Cancer Fund. The authors declare that there are no conflicts of interest.

Indices of methylation in sperm DNA from fertile men differ between distinct geographical regions.

STUDY QUESTION: Which are the main determinants, if any, of sperm DNA methylation levels? SUMMARY ANSWER: Geographical region resulted associated with the sperm methylation status assessed on genome-wide repetitive sequences. WHAT IS KNOWN ALREADY: DNA methylation level, assessed on repetitive sequences from peripheral blood lymphocyte, can vary with age, gender, alcohol consumption and white blood cell counts. STUDY DESIGN, SIZE, DURATION: A cross-sectional study. Individual data were collected from 269 young healthy men of proven fertility living in three geographical regions: Inuits from Greenland, Caucasians from Warsaw (Poland) and Kharkiv (Ukraine). Semen samples were collected between May 2002 and February 2004 and aliquots were immediately frozen. PARTICIPANTS/MATERIALS, SETTING, METHODS: We estimated sperm DNA global methylation level (DGML) in two ways. First DNA methylation in repetitive DNA sequences (LINE-1, Satα and Alu) was quantified by PCR pyrosequencing after bisulfite conversion and second by flow cytometry (FCM) using fluorescently labeled monoclonal antibodies anti-5-methylcytosine. We analyzed whether personal characteristics and habits, body mass index, semen quality parameters, sperm chromatin integrity, biomarkers of accessory gland function and the plasma concentration of reproductive hormones were associated with sperm DNA methylation levels in men. Associations were evaluated by analysis of variance and linear regression analyses. MAIN RESULTS AND THE ROLE OF CHANCE: The geographical location emerged as the main determinant when using the methylation level in repetitive sequences. FCM DGML results were not associated with those from repetitive sequence analysis. No other consistent associations between methylation markers and the assessed variables were identified across countries. LIMITATIONS, REASONS FOR CAUTION: The methods used are only surrogates of the actual sperm methylome and the methylation levels at individual specific loci were not explored. WIDER IMPLICATIONS OF THE FINDINGS: Sperm DGML is relatively independent from semen quality parameters and is a new candidate biomarker for epidemiological studies of the impact of environmental contaminants on male fertility. STUDY FUNDING/COMPETING INTERESTS: The study is part of the project CLEAR (Climate change, Environmental contaminants and Reproductive health) supported by the European Commission 7th framework program, contract no: FP7-ENV-2008-1-226217. No competing interest is declared.

Exposure to perfluorinated compounds and human semen quality in Arctic and European populations.

BACKGROUND: Perfluorinated compounds (PFCs) have been suspected to adversely affect human reproductive health. The aim of this study was to investigate the associations between PFC exposure and male semen quality. METHODS: PFCs were measured in serum from 588 partners of pregnant women from Greenland, Poland and Ukraine who provided a semen sample, using liquid chromatography tandem mass spectrometry. Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) could be detected in >97% of the samples. The associations between levels of these compounds and semen volume, sperm concentration, total sperm count, motility and morphology were assessed. RESULTS: Across countries, sperm concentration, total sperm count and semen volume were not consistently associated with PFOS, PFOA, PFHxS or PFNA levels. The proportion of morphologically normal cells was 35% lower [95% confidence interval (CI): 4-66%) for the third tertile of PFOS exposure as compared with the first. A similar reduction was found in relation to increasing PFHxS levels. At the third PFOA exposure tertile, the percentage of motile spermatozoa was 19% (95% CI: 1 to 39%) higher than in the first. CONCLUSIONS: The most robust finding in the present study was the negative associations between PFOS exposure and sperm morphology suggesting adverse effects of PFOS on semen quality, possibly due to interference with the endocrine activity or sperm membrane function. It cannot be excluded that this association and the positive association between PFOA and semen motility, which was not consistent across countries, might represent a chance finding due to the multiple statistical tests being performed.

[Well-being in call centres: a multidisciplinary approach to research and evaluation]. / Il benessere nei call center: un approccio multidisciplinare di ricerca e valutazione.

BACKGROUND: The topics of stress and well-being in call centres are the focus of many different disciplines. This article presents the definition and start-up phases of the "Well-being in Telecom Italia Call Centres" project, which was coordinated and supervised by an interdisciplinary scientific committee composed of members from different universities. To address the topic of individual well-being in the organizational context means considering all the main factors that can affect wellbeing. OBJECTIVES: For this reason, the study assessed the topic from three different view-points (psychological/sociological/cultural, physical/chemical/biological, organizational/technological/work-related) in order to obtain an accurate as possible picture of the complex well-being dynamics. METHODS: The study plan shows that merging qualitative methods (interviews, observations, focus-groups) and quantitative methods (questionnaires, physiological response to perceived stress) was a central concern for the research team. RESULTS: The collected data highlighted important differences between psychological and physical well-being and discomfort according to the different kinds of call centre, the respondents'gender and working hours. CONCLUSIONS: This method enabled us to define the specific features of call centre environments, leading to a definition of work in the centres as an activity with high psychological uncertainty, where rigid rules coexist with demands of high levels of flexibility and competence, and suggesting the importance of specific organizational measures in order to improve well-being.

Sperm chromatin integrity in DDT-exposed young men living in a malaria area in the Limpopo Province, South Africa.

BACKGROUND: There is mounting evidence that deteriorated semen quality may be associated with increased serum concentration of 1,1,1-trichloro-2,2-bis(chlorodiphenyl)ethane (DDT) and its metabolites. The problem is exacerbated in situations where DDT is the only resource available to control malaria mosquitoes and DDT metabolite plasma concentration can reach 1000-fold the level found in other populations. There are limited and contradictory epidemiological data on whether DDT/dichlorodiphenyl-dichloroethylene (DDE) can also damage sperm DNA. Therefore, there is a need to investigate the possible adverse effects on human sperm genetic integrity in a sufficiently large study population with adequate exposure contrasts, especially in the high exposure range. METHODS: We conducted a cross-sectional study, recruiting 209 young males from three communities in an endemic malaria area where DDT is sprayed annually. Blood plasma p,p'-DDT and its metabolite p,p'-DDE levels were measured and expressed as lipid adjusted p,p'-DDT and p,p'-DDE values. The sperm chromatin structure assay and Aniline Blue test were used to assess sperm DNA/chromatin integrity. RESULTS: The lipid adjusted p,p'-DDT mean (+/-SD) and median concentrations were 109.2 (+/-106.6) and 83.9 microg/g, respectively; and the lipid adjusted p,p'-DDE mean (+/-SD) and median concentrations were 246.2 (+/-218.5) and 177.8 microg/g, respectively. The results point to a weak association between DDT/DDE plasma concentration and the incidence of sperm with chromatin defects. CONCLUSIONS: The results suggest that non-occupational environmental DDT exposure may have a negative impact on sperm chromatin integrity in young South African males.

Sperm DNA integrity in cancer patients: the effect of disease and treatment.

As oncological treatment might impair the patients' fertility, male cancer patients are offered to cryopreserve semen prior to treatment. Impaired sperm DNA quality is associated with reduced fertility, and in case of assisted reproduction, sperm DNA integrity may have an impact on choice of method. Therefore, we have assessed sperm DNA integrity in cancer patients, comparing pre- and post-treatment quality. Sperm DNA integrity was investigated in cryopreserved semen from 121 cancer patients, the predominating diagnoses were germ cell cancer (GCC) and Hodgkin's lymphoma (HL). Post-treatment samples, with a median follow-up of 3 years, were analysed for 58 of the men, allowing a pre- and post-treatment analysis on an individual basis. Sperm DNA integrity was assessed using the Sperm Chromatin Structure Assay and expressed here as the DNA Fragmentation Index (DFI%). One hundred and thirty-seven fertile men served as controls. Before treatment, GCC (n = 84) and HL (n = 18) patients had higher DFI% than controls (n = 143) with a mean difference of 7.7 (95% CI 3.2-8.8) and 7.0 (95% CI 2-12), respectively. The same trend was observed for other cancer diagnoses, but without reaching statistical significance (mean difference 3.6, 95% CI -1.2 to 8.4). No increase was seen in DFI% comparing pre- and post-treatment semen, regardless of treatment modality. A moderate elevation of DFI% was observed in cryopreserved semen from cancer patients. Oncological treatment, generally, did not induce any increase in DFI. These findings should be considered when discussing the utilization of pre-treatment cryopreserved semen vs. post-treatment fresh sperm in cancer patients undergoing assisted reproduction.

Controlling cardiac chaos.

The extreme sensitivity to initial conditions that chaotic systems display makes them unstable and unpredictable. Yet that same sensitivity also makes them highly susceptible to control, provided that the developing chaos can be analyzed in real time and that analysis is then used to make small control interventions. This strategy has been used here to stabilize cardiac arrhythmias induced by the drug ouabain in rabbit ventricle. By administering electrical stimuli to the heart at irregular times determined by chaos theory, the arrhythmia was converted to periodic beating.

Toxicity and genotoxicity induced by abacavir antiretroviral medication alone or in combination with zidovudine and/or lamivudine in Drosophila melanogaster.

Abacavir (ABC), zidovudine (AZT), and lamivudine (3TC) are nucleoside analog reverse transcriptase inhibitors (NRTIs) widely used as combination-based antiretroviral therapy against human immunodeficiency virus. Despite effective viral suppression using NRTI combinations, genotoxic potential of NRTIs can be increased when administered in combination. This study investigated the toxic and genotoxic potential of ABC when administered alone or in combination with AZT and/or 3TC using the somatic mutation and recombination test in Drosophila melanogaster. This test simultaneously evaluated two events related to carcinogenic potential: mutation and somatic recombination. The results indicated that ABC was responsible for toxicity when administered alone or in combination with AZT and/or 3TC. In addition, all treatment combinations increased frequencies of mutation and somatic recombination. The combination of AZT/3TC showed the lowest genotoxic activity compared to all combinations with ABC. Therefore, our results indicated that ABC was responsible for a significant portion of genotoxic activity of these combinations. Somatic recombination was the main genetic event observed, ranging from 83.7% to 97.7%.

Neurobiological mechanisms of cannabinoid addiction.

The endocannabinoid system is implicated in the regulation of a variety of physiological processes, among which conditioning, motivation, habit forming, memory, learning, and cognition play pivotal roles in drug reinforcement and reward. In this article we will give a synopsis of last developments in research on cannabinoid actions on brain reward circuits coming from behavioral, neurochemical and electrophysiological studies. Central cannabinoid-induced effects as measured by animal models of addiction, in vivo cerebral microdialysis, in vitro and in vivo electrophysiological recording techniques, will be reviewed. Brain sites that have been implicated in the mediation of addictive cannabinoid properties include primarily the ventral tegmental area, the nucleus accumbens, and the medial prefrontal cortex, although the amygdala, the substantia nigra, the globus pallidus, and the hippocampus have also been shown to be critical structures mediating motivational and reinforcing effects of cannabinoids. Putative neurobiological mechanisms underlying these effects will be delineated.

Inhibitory effects of water extract of propolis on doxorubicin-induced somatic mutation and recombination in Drosophila melanogaster.

Propolis is a substance produced by honeybees (Apis mellifera L.). Its components are strong antioxidants and free radical scavengers. The aim of this study was to evaluate the protective effects of a water extract of Brazilian green propolis (WEP) combined with the antitumor agent doxorubicin (DXR) on Drosophila melanogaster wing cells through the somatic mutation and recombination test (SMART). Two different crosses were used: The standard (ST) cross and the high bioactivation (HB) cross. The HB cross is characterized by a constitutively enhanced level of cytochrome P450 which leads to an increased sensitivity to a number of promutagens and procarcinogens. Larvae obtained from these two crosses were chronically treated with different concentrations of WEP (12.5,25.0 and 50.0 mg/mL) alone or combined with DXR (0.125 mg/mL). The results obtained with the two different crosses were rather similar. Neither toxicity nor genotoxicity were observed in WEP treated series. Simultaneous treatment with different concentrations of WEP and DXR led to a reduction in the frequency of recombination compared to the treatment with DXR alone. This anti-recombinogenic effect was proportional to the concentrations applied, indicating a dose-response correlation and can be attributed to the powerful scavenger ability of WEP.

An endocannabinoid mechanism in relapse to drug seeking: a review of animal studies and clinical perspectives.

Detoxification from drug abuse is strongly threatened by the occurrence of renewed episodes of drug intake. In human addicts, relapse to drug seeking may take place even after a considerably long period from the last drug consumption. Over the last decade, the endocannabinoid system has received remarkable attention due to its unique features, including its rewarding properties closely resembling those of the most commonly abused substances and its multiple therapeutic implications. Although limited at present, evidence is now emerging on a possible participation of the endogenous cannabinoid system in the regulation of relapsing phenomena. Both stimulation and blockade of the central cannabinoid CB-sub1 receptor have proved to play an important role in drug- as well as in cue-induced reinstatement of drug seeking behavior. Indeed, while CB-sub1 receptor stimulation may elicit relapse not only to cannabinoid seeking but also to cocaine, heroin, alcohol and methamphetamine, this effect is significantly attenuated, when not fully prevented, by pretreatment with the CB-sub1 receptor antagonist rimonabant. However, corroborating data on the involvement of the cannabinoid system in stress-induced reinstatement are still rather scarce. The present review attempts to collect data obtained from different laboratories using diverse experimental approaches, to provide a comprehensive picture of the recent evidence of a relationship between the cannabinoid system and the neurobiological mechanisms leading to relapse. For each class of abused drugs, the conspicuous progress made in delineating the role of the endocannabinoid system in relapse to drug seeking has been examined by placing particular emphasis on the findings obtained from behavioral studies. After summarizing findings and implications emerging from the reviewed studies, we conclude by briefly discussing what information is still missing and how missing information might be obtained.

Prenatal cannabis exposure increases heroin seeking with allostatic changes in limbic enkephalin systems in adulthood.

BACKGROUND: Prenatal cannabis exposure is a growing concern with little known about the long-term consequences on behavior and neural systems relevant for reward and emotional processing. METHODS: We used an animal model to study the effects of prenatal exposure to Delta(9)-tetrahydrocannabinol (THC) on heroin self-administration behavior and opioid neural systems in adult males (postnatal day 62). Rats were exposed to THC (.15 mg/kg) or vehicle from gestational day 5 to postnatal day 2. RESULTS: Both pretreatment groups showed similar heroin intake, but THC-exposed rats exhibited shorter latency to the first active lever press, responded more for low heroin doses, and had higher heroin-seeking during mild stress and drug extinction. THC exposure reduced preproenkephalin (PENK) mRNA expression in the nucleus accumbens during early development, but was elevated in adulthood; no adult striatal changes on preprodynorphin mRNA or PENK in caudate-putamen. PENK mRNA was also increased in the central and medial amygdala in adult THC-exposed animals. THC animals had reduced heroin-induced locomotor activity and nucleus accumbens mu opioid receptor coupling. CONCLUSIONS: This study demonstrates enduring effects of prenatal THC exposure into adulthood that is evident on heroin-seeking behavior during extinction and allostatic changes in mesocorticolimbic PENK systems relevant to drug motivation/reward and stress response.

Strain and schedule-dependent differences in the acquisition, maintenance and extinction of intravenous cannabinoid self-administration in rats.

Cannabinoids have been reported to sustain self-administration in laboratory animals; however, genetic differences and environmental factors critical in the initiation and retention of such behaviour are yet to be defined. This study investigated the acquisition, maintenance and extinction of self-administration of the cannabinoid CB1 receptor agonist WIN 55,212-2 (6.25-25 microg/kg/inf) in Long Evans, Lister Hooded and Sprague-Dawley rats under a continuous schedule of reinforcement and two different response-like operanda, nose-poking and lever-pressing. Results showed that Long Evans and Lister Hooded, but not Sprague Dawley, rats acquired and retained stable cannabinoid self-administration behaviour under both modus operandi, as defined by significant differences between responding in the active versus the inactive hole/lever. In rats developing firm self-administration, substitution of saline for WIN 55,212-2 extinguished the responding, supporting the notion that cannabinoids may serve as a positive reinforcer in laboratory animals. Nevertheless, significant differences among strains and responding modalities were observed in the percentage of acquisition, amount of drug intake during maintenance and timing of extinction. In addition, no significant strain differences were found in motor response to WIN 55,212-2 (0.3 and 3.0 mg/kg), thus excluding that strain differences observed during cannabinoid self-administration could be related to different cannabinoid-induced locomotor effects.

Cannabinoid self-administration in rats: sex differences and the influence of ovarian function.

BACKGROUND AND PURPOSE: We recently demonstrated the existence of strain differences in self-administration of the cannabinoid CB1 receptor agonist WIN55,212-2 (WIN) by Long Evans (LE) and Lister Hooded (LH) but not Sprague-Dawley (SD) male rats. This follow-up study is aimed at verifying whether sex and ovarian hormones might also be critical factors in the initiation, retention and extinction of WIN self-administration. EXPERIMENTAL APPROACH: LE, LH and SD male and female rats, the latter either intact or bilaterally ovariectomized (OVX), were trained to self-administer WIN (12.5 microg kg(-1) per infusion) under a FR1 reinforcement schedule, using lever-pressing. KEY RESULTS: Data showed that contrary to the findings in SD rats, LE and LH rats developed robust cannabinoid intake, with rates of responding for WIN being constantly higher in intact females than in males (+45 and +42% for LE and LH strains, respectively). In comparison with intact females, OVX females of both strains acquired self-administration at lower rates, displaying slower acquisition, lower drug intake (-42 and -52% for LE and LH, respectively) and longer extinction. CONCLUSIONS AND IMPLICATIONS: These findings provide the first evidence of significant sex differences in cannabinoid self-administration, females acquiring stable WIN intake at higher rates and more rapidly than males. Moreover, when compared to intact females, a lower percentage of LE and LH OVX rats acquired and maintained stable drug intake, suggesting that ovarian hormones might represent a critical factor in modulating the reinforcing effect of cannabinoids.

Sperm chromatin structure and male fertility: biological and clinical aspects.

Sperm chromatin/DNA integrity is essential for the accurate transmission of paternal genetic information, and normal sperm chromatin structure is important for sperm fertilizing ability. The routine examination of semen, which includes sperm concentration, motility and morphology, does not identify defects in sperm chromatin structure. The origin of sperm DNA damage and a variety of methods for its assessment are described. Evaluation of sperm DNA damage appears to be a useful tool for assessing male fertility potential both in vivo and in vitro. The possible impact of sperm DNA defects on the offspring is also discussed.

Chaos control of cardiac arrhythmias.

Chaos theory has shown that many disordered and erratic phenomena are in fact deterministic, and can be understood causally and controlled. The prospect that cardiac arrhythmias might be instances of deterministic chaos is therefore intriguing. We used a recently developed method of chaos control to stabilize a ouabain-induced arrhythmia in rabbit ventricular tissue in vitro. Extension of these results to clinically significant arrhythmias such as fibrillation will require overcoming the additional obstacles of spatiotemporal complexity.

Use of hematopoietic cytokines to accelerate the recovery of the immune system in irradiated mice.

In our previous studies aimed at designing appropriate strategies to accelerate recovery of the immune system after irradiation, we found that the hematopoietic cytokine recombinant murine (rmu) interleukin (IL)-3 was able to induce differentiation and growth of thymocytes and splenic T and B lymphocytes in mice exposed to x-rays (200-500 cGy). The recovery, however, was complete at 7 days only after a dose of 200 cGy, whereas 2, 3, and 4 weeks were necessary to achieve full recovery after 300, 400, and 500 cGy, respectively. These studies were extended to investigate the effects of another hematopoietic cytokine, recombinant human (rhu) IL-11, a bone marrow stromal-derived cytokine, administered together with IL-3 to irradiated mice. The synergistic effect of the two cytokines was evident when relatively small doses of rhu IL-11 were injected with an optimal dose of rmu IL-3.

Testicular cancer and sperm DNA damage: short- and long-term effects of antineoplastic treatment.

The aim of this study was to investigate sperm DNA damage induced by chemo- and radiotherapy in patients with testicular cancer to provide data on the extent and persistence of nuclear damage that might affect individual reproductive potential. We evaluated pre- and post-antineoplastic treatment sperm DNA integrity, expressed as DNA Fragmentation Index (DFI), in a large caseload of testicular cancer patients by sperm chromatin structure assay. The mean total DFI for all patients at T0 was 18.0 ± 12.5%. Sperm chromatin profile was markedly impaired at T3 (27.7 ± 17.4%) and T6 (23.2 ± 15.3%), improving considerably at T12 and T24 (14.0 ± 8.9% and 14.4 ± 10.3%). After chemotherapy, we found a marked increase in DFI at T3 and T6 and a significant reduction at T12 and T24 in comparison with the baseline. In contrast, DFI increased at T3 and T6 after radiotherapy but the subsequent reduction was far less marked, reaching baseline values at T12 and T24. Finally, post-treatment DNA damage was not age or histotype dependent, but was more marked in the advanced stage of cancer. In this study, we showed that the chromatin profile may be affected in the months immediately following the end of the treatment, improving after 12-24 months. Our results thus indicate that post-treatment DNA damage is influenced both by the type and intensity of the therapy and by the pathological and clinical stage of the disease.

Body-composition changes with diet and exercise in obese women: a comparison of estimates from clinical methods and a 4-component model.

BACKGROUND: Most methods available to clinicians for estimating body-composition changes have been validated against estimates from densitometry, based on a 2-component (fat mass and fat-free mass) model. OBJECTIVE: Estimates of changes in percentage body fat (%BF) from dual-energy X-ray absorptiometry (DXA), skinfold thicknesses (SFTs), bioelectrical impedance analysis (BIA), and body mass index (BMI; in kg/m2) were compared with estimates from a 4-component (fat, water, mineral, and protein) model (%BFd,w,m), a more accurate method. DESIGN: Determinations of body density from hydrostatic weighing, body water from deuterium dilution, bone mineral and %BF from whole-body DXA, resistance from BIA, and anthropometric measures were made in 27 obese women (BMI: 31.1 +/- 4.9) assigned to 1 of 3 groups: control (C; n = 9), diet only (DO; n = 9), or diet plus aerobic exercise (DE; n = 9). RESULTS: After the 16-wk intervention, changes in body mass (BM) averaged 0.5 +/- 2.0, -7.2 +/- 7.4, and -4.0 +/- 3.3 kg and changes in %BFd,w,m averaged 2.1 +/- 1.0%, -1.2 +/- 1.4%, and -2.4 +/- 1.6% in the C, DO, and DE groups, respectively. Compared with changes in %BFd,w,m, the errors (SD of bias) for estimates of changes in %BF by DXA, BIA, SFTs, and BMI were similar (range: +/-2.0-2.4% of BM). BIA, SFTs, and BMI provided unbiased estimates of decreases in %BFd,w,m, but DXA overestimated decreases in %BF in the DO and DE groups. CONCLUSIONS: DXA, BIA, SFTs, and BMI are comparably accurate for evaluating body-composition changes induced by diet and exercise interventions; however, small changes in %BF may not be accurately detected by these clinical methods.