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      The Relationship of Urinary Metabolites of Carbaryl/Naphthalene and Chlorpyrifos with Human Semen Quality

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          Abstract

          Most of the general population is exposed to carbaryl and other contemporary-use insecticides at low levels. Studies of laboratory animals, in addition to limited human data, show an association between carbaryl exposure and decreased semen quality. In the present study we explored whether environmental exposures to 1-naphthol (1N), a metabolite of carbaryl and naphthalene, and 3,5,6-trichloro-2-pyridinol (TCPY), a metabolite of chlorpyrifos and chlorpyrifos-methyl, are associated with decreased semen quality in humans. Subjects ( n = 272) were recruited through a Massachusetts infertility clinic. Individual exposures were measured as spot urinary concentrations of 1N and TCPY adjusted using specific gravity. Semen quality was assessed as sperm concentration, percent motile sperm, and percent sperm with normal morphology, along with sperm motion parameters (straight-line velocity, curvilinear velocity, and linearity). Median TCPY and 1N concentrations were 3.22 and 3.19 μg/L, respectively. For increasing 1N tertiles, adjusted odds ratios (ORs) were significantly elevated for below-reference sperm concentration (OR for low, medium, and high tertiles = 1.0, 4.2, 4.2, respectively; p-value for trend = 0.01) and percent motile sperm (1.0, 2.5, 2.4; p-value for trend = 0.01). The sperm motion parameter most strongly associated with 1N was straight-line velocity. There were suggestive, borderline-significant associations for TCPY with sperm concentration and motility, whereas sperm morphology was weakly and nonsignificantly associated with both TCPY and 1N. The observed associations between altered semen quality and 1N are consistent with previous studies of carbaryl exposure, although suggestive associations with TCPY are difficult to interpret because human and animal data are currently limited.

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          Interpretation of urine results used to assess chemical exposure with emphasis on creatinine adjustments: a review.

          This paper reviews the process of elimination of creatinine (CRE), and the limitations presented when using it to express urine concentrations. This literature review leads to three conclusions: (1) CRE excretion is subject to wide fluctuations due to specific internal and external factors; (2) the use of CRE to correct chemical concentrations in urine will not necessarily improve the correlation to the exposure dose for all chemicals (it may, in fact, worsen the result); and (3) other means of expressing urine concentration may offer greater accuracy towards estimating individually absorbed dose.
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            Role of reactive oxygen species in male infertility.

            Human spermatozoa exhibit a capacity to generate ROS and initiate peroxidation of the unsaturated fatty acids in the sperm plasma membrane, which plays a key role in the etiology of male infertility. The short half-life and limited diffusion of these molecules is consistent with their physiologic role in key biological events such as acrosome reaction and hyperactivation. The intrinsic reactivity of these metabolites in peroxidative damage induced by ROS, particularly H2O2 and the superoxide anion, has been proposed as a major cause of defective sperm function in cases of male infertility. The number of antioxidants known to attack different stages of peroxidative damage is growing, and it will be of interest to compare alpha-tocopherol and ascorbic acid with these for their therapeutic potential in vitro and in vivo. Both spermatozoa and leukocytes generate ROS, although leukocytes produce much higher levels. The clinical significance of leukocyte presence in semen is controversial. Seminal plasma confers some protection against ROS damage because it contains enzymes that scavenge ROS, such as catalase and superoxide dismutase. A variety of defense mechanisms comprising a number of anti-oxidants can be employed to reduce or overcome oxidative stress caused by excessive ROS. Determination of male infertility etiology is important, as it will help us develop effective therapies to overcome excessive ROS generation. ROS can have both beneficial and detrimental effects on the spermatozoa and the balancing between the amounts of ROS produced and the amounts scavenged at any moment will determine whether a given sperm function will be promoted or jeopardized. Accurate assessment of ROS levels and, subsequently, OS is vital, as this will help clinicians both elucidate the fertility status and identify the subgroups of patients that respond or do not respond to these therapeutic strategies. The overt commercial claims of antioxidant benefits and supplements for fertility purposes must be cautiously looked into, until proper multicentered clinical trials are studied. From the current data it appears that no single adjuvant will be able to enhance the fertilizing capacity of sperm in infertile men, and a combination of the possible strategies that are not toxic at the dosage used would be a feasible approach.
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              Relationship between oxidative stress, semen characteristics, and clinical diagnosis in men undergoing infertility investigation.

              To determine whether particular semen characteristics in various clinical diagnoses of infertility are associated with high oxidative stress and whether any group of infertile men is more likely to have high seminal oxidative stress. Reactive oxygen species (ROS) play an important role in sperm physiological functions, but elevated levels of ROS or oxidative stress are related to male infertility. Measurement of sperm concentration, motility, morphology, seminal ROS, and total antioxidant capacity (TAC) in patients seeking infertility treatment and controls. Male infertility clinic of a tertiary care center. One hundred sixty-seven infertile patients and 19 controls. None. Semen characteristics, seminal ROS, and TAC in samples from patients with various clinical diagnoses and controls. Fifteen patients (9.0%) were Endtz positive and 152 (91.0%) Endtz negative. Sperm concentration, motility, and morphology were significantly reduced in all groups compared with the controls (P =.02), except in varicocele associated with infection group. Mean (+/-SD) ROS levels in patient groups ranged from 2.2 +/- 0.13 to 3.2 +/- 0.35, significantly higher than controls (1.3 +/- 0.3; P<.005). Patient groups had a significantly lower mean (+/-SD) TAC from 1014.75 +/- 79.22 to 1173.05 +/- 58.07 than controls (1653 +/- 115.28, P<.001), except in the vasectomy reversal group (1532.02 +/- 74.24). Sperm concentration was negatively correlated with ROS both overall and within all groups (P
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                Author and article information

                Journal
                Environ Health Perspect
                Environmental Health Perspectives
                0091-6765
                December 2004
                7 September 2004
                : 112
                : 17
                : 1665-1670
                Affiliations
                1Department of Environmental Health and
                2Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA
                3Centers for Disease Control and Prevention, Atlanta, Georgia, USA
                Author notes

                Address correspondence to R. Hauser, Department of Environmental Health, Occupational Health Program, Harvard School of Public Health, Building 1, Room 1405, 665 Huntington Ave., Boston, MA 02115 USA. Telephone: (617) 432-3326. Fax: (617) 432-0219. E-mail: rhauser@ 123456hohp.harvard.edu

                We thank L. Godfrey-Bailey who recruited the study patients and collected the biological specimens; J. Frelich who was responsible for data management; and A. Trisini and R. Dadd, who assisted with manuscript preparation and literature reviews.

                This work was supported by grants ES09718 and ES00002 from the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH).

                Contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS or the NIH.

                The authors declare they have no competing financial interests.

                Article
                ehp0112-001665
                10.1289/ehp.7234
                1253656
                15579410
                058ebf38-4a31-447a-9950-4c51f4e00b58
                This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI.
                History
                : 6 May 2004
                : 7 September 2004
                Categories
                Research
                Articles

                Public health
                semen,environment,pesticides,biological markers,human
                Public health
                semen, environment, pesticides, biological markers, human

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