Male Reproductive Impacts - HH-RA.org

Bibliography Tag: male reproductive impacts

Anway et al., 2005

Anway, Matthew D., Cupp, Andrea S., Uzumcu, Mehmet, and Skinner, Michael K., “Epigenetic Transgenerational Actions of Endocrine Disruptors and Male Fertility,” Science, 2005, 308:5727, DOI: 10.1126/SCIENCE.1108190.

ABSTRACT:

Transgenerational effects of environmental toxins require either a chromosomal or epigenetic alteration in the germ line. Transient exposure of a gestating female rat during the period of gonadal sex determination to the endocrine disruptors vinclozolin (an antiandrogenic compound) or methoxychlor (an estrogenic compound) induced an adult phenotype in the F1 generation of decreased spermatogenic capacity (cell number and viability) and increased incidence of male infertility. These effects were transferred through the male germ line to nearly all males of all subsequent generations examined (that is, F1 to F4). The effects on reproduction correlate with altered DNA methylation patterns in the germ line. The ability of an environmental factor (for example, endocrine disruptor) to reprogram the germ line and to promote a transgenerational disease state has significant implications for evolutionary biology and disease etiology. FULL TEXT

Swan et al., 2003

Swan SH, Kruse RL, Liu F, Barr DB, Drobnis EZ, Redmon JB, Wang C, Brazil C, Overstreet JW, “Semen quality in relation to biomarkers of pesticide exposure,” Environmental Health Perspectives, 2003, 111:12.

ABSTRACT: We previously reported reduced sperm concentration and motility in fertile men in a U.S. agrarian area (Columbia, MO) relative to men from U.S. urban centers (Minneapolis, MN; Los Angeles, CA; New York, NY). In the present study we address the hypothesis that pesticides currently used in agriculture in the Midwest contributed to these differences in semen quality. We selected men in whom all semen parameters (concentration, percentage sperm with normal morphology, and percentage motile sperm) were low (cases) and men in whom all semen parameters were within normal limits (controls) within Missouri and Minnesota (sample sizes of 50 and 36, respectively) and measured metabolites of eight current-use pesticides in urine samples provided at the time of semen collection. All pesticide analyses were conducted blind with respect to center and case-control status. Pesticide metabolite levels were elevated in Missouri cases, compared with controls, for the herbicides alachlor and atrazine and for the insecticide diazinon [2-isopropoxy-4-methyl-pyrimidinol (IMPY)]; for Wilcoxon rank test, p = 0.0007, 0.012, and 0.0004 for alachlor, atrazine, and IMPY, respectively. Men from Missouri with high levels of alachlor or IMPY were significantly more likely to be cases than were men with low levels [odds ratios (ORs) = 30.0 and 16.7 for alachlor and IMPY, respectively], as were men with atrazine levels higher than the limit of detection (OR = 11.3). The herbicides 2,4-D (2,4-dichlorophenoxyacetic acid) and metolachlor were also associated with poor semen quality in some analyses, whereas acetochlor levels were lower in cases than in controls (p = 0.04). No significant associations were seen for any pesticides within Minnesota, where levels of agricultural pesticides were low, or for the insect repellent DEET (N,N-diethyl-m-toluamide) or the malathion metabolite malathion dicarboxylic acid. These associations between current-use pesticides and reduced semen quality suggest that agricultural chemicals may have contributed to the reduction in semen quality in fertile men from mid-Missouri we reported previously. FULL TEXT

Swan, 2006

Swan SH, “Semen quality in fertile US men in relation to geographical area and pesticide exposure,” International Journal of Andrology, 2006, 29:1.

ABSTRACT: We conducted the first US study to compare semen quality among study centres using standardized methods and strict quality control. We present data on semen quality in partners of 493 pregnant women recruited through prenatal clinics in four US cities during 1999-2001. Sperm concentration, semen volume and motility were determined at the centres and morphology was assessed at a central laboratory. While between-centre differences in sperm morphology and sample volume were small, sperm concentration and motility were significantly reduced in Columbia, MO (MO) relative to men in New York, NY, Minneapolis, MN and Los Angeles, CA; total number of motile sperm was 113 x 10(6) in MO and 162, 201 and 196 x 10(6) in CA, MN and NY respectively. Differences among centres remained significant in multivariate models that controlled for abstinence time, semen analysis time, age, race, smoking, history of sexually transmitted disease and recent fever (all p-values <0.01). We hypothesized that poorer sperm concentration and motility in MO men relative to other centres might be related to agricultural pesticides that are commonly used in the mid-west. We investigated this hypothesis by conducting a nested case-control study within the MO cohort. We selected 25 men in this cohort for whom all semen parameters (concentration, % normal morphology and % motile) were low as cases and an equal number of men for whom all semen parameters were within normal limits as controls. We measured metabolites of eight non-persistent, current-use pesticides in urine samples the men had provided at the time of semen collection. Pesticide metabolite levels were elevated in cases compared with controls for the herbicides alachlor and atrazine, and for the insecticide diazinon (2-isopropoxy-4-methyl-pyrimidinol) (p-values for Wilcoxon rank test = 0.0007, 0.012, and 0.0004 for alachlor, atrazine and diazinon respectively). Men with higher levels of alachlor or diazinon were significantly more likely to be cases than men with low levels [odds ratios (OR) = 30.0, 16.7 for alachlor and diazinon respectively], as were men with atrazine over the limit of detection (OR = 11.3). These associations between current-use pesticides and reduced semen quality suggest that agricultural chemicals may have contributed to the reduced semen quality seen in fertile men from mid-Missouri.

Rocheleau et al., 2009

Rocheleau CM, Romitti PA, Dennis LK, “Pesticides and hypospadias: a meta-analysis.,” Journal of Pediatric Urology, 2009, 5:1, DOI: 10.1016/j.jpurol.2008.08.006.

ABSTRACT:

OBJECTIVE: To use meta-analytic techniques to synthesize the findings of the current body of published literature regarding the risk of hypospadias resulting from parental exposure to pesticides.

MATERIALS AND METHODS: A search of Pub Med for original research published in English from January 1966 through March 2008 identified 552 studies, 90 of which were reviewed in detail. Nine studies met all study inclusion criteria. Two reviewers independently abstracted data from each included study. Any disagreements were resolved by consensus. Pooled risk ratios (PRRs) and confidence intervals (CIs) were calculated using both random and fixed effects models, along with statistical tests of homogeneity.

RESULTS: Elevated but marginally significant risks of hypospadias were associated with maternal occupational exposure (PRR of 1.36, CI=1.04-1.77), and paternal occupational exposure (PRR of 1.19, CI=1.00-1.41). Subgroup analyses provided insights into needed designs for future studies. Notably, exposure assessment using a job-exposure matrix resulted in slightly higher estimated risk than agricultural occupation in fathers; but this effect was reversed in mothers, suggesting the importance of indirect and residential pesticide exposures in this group.

CONCLUSIONS: Despite potential exposure misclassification, which would tend to diminish observed associations, the previous literature indicates a modestly increased risk of hypospadias associated with pesticide exposure. FULL TEXT

Omoike et al., 2015

Omoike OE, Lewis RC, Meeker JD, “Association between urinary biomarkers of exposure to organophosphate insecticides and serum reproductive hormones in men from NHANES 1999-2002,” Reproductive Toxicology, 2015, 53, DOI: 10.1016/j.reprotox.2015.04.005.

ABSTRACT: Exposure to organophosphate (OP) insecticides may alter reproductive hormone levels in men and increase the risk for poor reductive health and other adverse health outcomes. However, relevant epidemiology studies in men are limited. We evaluated urinary concentrations of OP metabolites (3,5,6-trichloro-2-pyridinol and six dialkyl phosphates) in relation to serum concentrations of testosterone (T) and estradiol among 356 men aged 20-55 years old from the U.S. National Health and Nutrition Examination Survey. Biomarkers were detected in greater than 50% of the samples, except for diethyldithiophosphate, dimethylphosphate, and dimethyldithiophosphate. In adjusted regression models, we observed a statistically significant inverse relationship between diethyl phosphate (DEP) and T when DEP was modeled as either a continuous or categorical variable. These findings add to the limited evidence that exposure to certain OP insecticides is linked to altered T in men, which may have important implications for male health. FULL TEXT

Manikkam et al., 2012b

Manikkam M, Guerrero-Bosagna C, Tracey R, Haque MM, Skinner MK, “Transgenerational actions of environmental compounds on reproductive disease and identification of epigenetic biomarkers of ancestral exposures,” PLoS One, 2012, 7:2.

ABSTRACT:

Environmental factors during fetal development can induce a permanent epigenetic change in the germ line (sperm) that then transmits epigenetic transgenerational inheritance of adult-onset disease in the absence of any subsequent exposure. The epigenetic transgenerational actions of various environmental compounds and relevant mixtures were investigated with the use of a pesticide mixture (permethrin and insect repellant DEET), a plastic mixture (bisphenol A and phthalates), dioxin (TCDD) and a hydrocarbon mixture (jet fuel, JP8). After transient exposure of F0 gestating female rats during the period of embryonic gonadal sex determination, the subsequent F1-F3 generations were obtained in the absence of any environmental exposure. The effects on the F1, F2 and F3 generations pubertal onset and gonadal function were assessed. The plastics, dioxin and jet fuel were found to promote early-onset female puberty transgenerationally (F3 generation). Spermatogenic cell apoptosis was affected transgenerationally. Ovarian primordial follicle pool size was significantly decreased with all treatments transgenerationally. Differential DNA methylation of the F3 generation sperm promoter epigenome was examined. Differential DNA methylation regions (DMR) were identified in the sperm of all exposure lineage males and found to be consistent within a specific exposure lineage, but different between the exposures. Several genomic features of the DMR, such as low density CpG content, were identified. Exposure-specific epigenetic biomarkers were identified that may allow for the assessment of ancestral environmental exposures associated with adult onset disease. FULL TEXT

Manikkam et al., 2012

Manikkam M, Tracey R, Guerrero-Bosagna C, Skinner MK, “Pesticide and insect repellent mixture (permethrin and DEET) induces epigenetic transgenerational inheritance of disease and sperm epimutations,” Reproductive Toxicology, 2012, 34:4, DOI: 10.1016/j.reprotox.2012.08.010.

ABSTRACT:

Environmental compounds are known to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a “pesticide mixture” (pesticide permethrin and insect repellent N,N-diethyl-meta-toluamide, DEET) promotes epigenetic transgenerational inheritance of disease and associated DNA methylation epimutations in sperm. Gestating F0 generation female rats were exposed during fetal gonadal sex determination and the incidence of disease evaluated in F1 and F3 generations. There were significant increases in the incidence of total diseases in animals from pesticide lineage F1 and F3 generation animals. Pubertal abnormalities, testis disease, and ovarian disease (primordial follicle loss and polycystic ovarian disease) were increased in F3 generation animals. Analysis of the pesticide lineage F3 generation sperm epigenome identified 363 differential DNA methylation regions (DMR) termed epimutations. Observations demonstrate that a pesticide mixture (permethrin and DEET) can promote epigenetic transgenerational inheritance of adult onset disease and potential sperm epigenetic biomarkers for ancestral environmental exposures. FULL TEXT

Manfo et al., 2012

Manfo FP, Moundipa PF, Déchaud H, Tchana AN, Nantia EA, Zabot MT, Pugeat M, “Effect of agropesticides use on male reproductive function: a study on farmers in Djutitsa (Cameroon),” Environmental Toxicology, 2012, 27:7, DOI: 10.1002/tox.20656.

ABSTRACT: This study aimed at investigating the effect of agropesticides on male reproductive function in farmers in Djutitsa (West Cameroon). To this end, 47 farmers in Djutitsa were asked questions on their health status and pesticide use in agriculture. Thereafter, their blood samples were collected for assessment of sex hormones including serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), androstenedione, testosterone, as well as sex hormone binding globulin (SHBG). Their serum triiodothyronine (T3) and thyroxine (T4) levels were also measured. Thirty seven men not exposed to agropesticides were recruited as control group. Fifty six pesticides containing 25 active substances were currently used by farmers enrolled in our study, and most of their symptoms were related to spread/use of these chemicals. Compared to the control group, there was no significant difference in FSH, LH, SHBG, estradiol, and thyroid hormones (T3 and T4) levels. Farmers had significantly lower serum testosterone (20.93 ± 1.03 nM vs. 24.32 ± 1.32 nM; P < 0.05) and higher androstenedione level (3.83 ± 0.20 nM vs. 2.80 ± 0.15 nM; P < 0.001). Their serum free testosterone as well as bioavailable testosterone were unchanged, while estradiol/testosterone and androstenedione/testosterone ratios were significantly increased (0.45 ± 0.03% vs. 0.33 ± 0.02%; P < 0.01 and 12.26 ± 3.64 vs 19.31 ± 6.82; P < 0.001, respectively). Our results suggest that male farmers of Djutitsa (West Cameroon) are exposed to agropesticides due to improper protective tool, and this exposure may impair their reproductive function through inhibition of testosterone synthesis; probably by inhibition of testicular 17β- hydroxysteroid dehydrogenase (17HSD3) and induction of aromatase (CYP19).

Garry et al., 2003

Garry VF, Holland SE, Erickson LL, Burroughs BL, “Male reproductive hormones and thyroid function in pesticide applicators in the Red River Valley of Minnesota,” Journal of Toxicology and Environmental Health – Part A, 2003, 66:11.

ABSTRACT: In the present effort, 144 pesticide applicators and 49 urban control subjects who reported no chronic disease were studied. Applicators provided records of the season’s pesticides used by product, volumes, dates, and methods of application. Blood specimens for examination of hormone levels were obtained in summer and fall. In the herbicide-only applicator group, significant increases in testosterone levels in fall compared to summer and also elevated levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the fall were noted. With respect to fungicide use, in an earlier cross-sectional epidemiologic study, data demonstrated that historic fungicide use was associated with a significant alteration of the sex ratio of children borne to applicators. As before, among current study subjects it was noted that historic fungicide use was associated with increased numbers of girls being born. Lower mean total testosterone concentrations by quartile were also correlated with increased numbers of live-born female infants. A downward summer to fall seasonal shift in thyroid-stimulating hormone (TSH) concentrations occurred among applicators but not among controls. Farmers who had aerial application of fungicides to their land in the current season showed a significant shift in TSH values (from 1.75 to 1.11 mU/L). Subclinical hypothyroidism was noted in 5/144 applicators (TSH values >4.5 mU/L), but not in urban control subjects. Based on current and past studies, it was concluded that, in addition to pesticide exposure, individual susceptibility and perhaps economic factors may play a supporting role in the reported results.

Clair et al., 2012

Clair E, Mesnage R, Travert C, Séralini GÉ, “A glyphosate-based herbicide induces necrosis and apoptosis in mature rat testicular cells in vitro, and testosterone decrease at lower levels,” Toxicology In Vitro, 2012, 26:2, doi: 10.1016/j.tiv.2011.12.009.

ABSTRACT: The major herbicide used worldwide, Roundup, is a glyphosate-based pesticide with adjuvants. Glyphosate, its active ingredient in plants and its main metabolite (AMPA) are among the first contaminants of surface waters. Roundup is being used increasingly in particular on genetically modified plants grown for food and feed that contain its residues. Here we tested glyphosate and its formulation on mature rat fresh testicular cells from 1 to 10000ppm, thus from the range in some human urine and in environment to agricultural levels. We show that from 1 to 48h of Roundup exposure Leydig cells are damaged. Within 24-48h this formulation is also toxic on the other cells, mainly by necrosis, by contrast to glyphosate alone which is essentially toxic on Sertoli cells. Later, it also induces apoptosis at higher doses in germ cells and in Sertoli/germ cells co-cultures. At lower non toxic concentrations of Roundup and glyphosate (1ppm), the main endocrine disruption is a testosterone decrease by 35%. The pesticide has thus an endocrine impact at very low environmental doses, but only a high contamination appears to provoke an acute rat testicular toxicity. This does not anticipate the chronic toxicity which is insufficiently tested, and only with glyphosate in regulatory tests.

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