Urinary Concentrations of Parabens and Serum Hormone Levels, Semen Quality Parameters, and Sperm DNA Damage

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Abstract

Background

Parabens are commonly used as antimicrobial preservatives in cosmetics, pharmaceuticals, and food and beverage processing. Widespread human exposure to parabens has been recently documented, and some parabens have demonstrated adverse effects on male reproduction in animal studies. However, human epidemiologic studies are lacking.

Objective

We investigated relationships between urinary concentrations of parabens and markers of male reproductive health in an ongoing reproductive epidemiology study.

Methods

Urine samples collected from male partners attending an infertility clinic were analyzed for methyl paraben (MP), propyl paraben (PP), butyl paraben (BP), and bisphenol A (BPA). Associations with serum hormone levels ( n = 167), semen quality parameters ( n = 190), and sperm DNA damage measures ( n = 132) were assessed using multivariable linear regression.

Results

Detection rates in urine were 100% for MP, 92% for PP, and 32% for BP. We observed no statistically significant associations between MP or PP and the outcome measures. Categories of urinary BP concentration were not associated with hormone levels or conventional semen quality parameters, but they were positively associated with sperm DNA damage ( p for trend = 0.03). When urinary BPA quartiles were added to the model, BP and BPA were both positively associated with sperm DNA damage ( p for trend = 0.03). Assessment of paraben concentrations measured on repeated urine samples from a subset of the men ( n = 78) revealed substantial temporal variability.

Conclusions

We found no evidence for a relationship between urinary parabens and hormone levels or semen quality, although intraindividual variability in exposure and a modest sample size could have limited our ability to detect subtle relationships. Our observation of a relationship between BP and sperm DNA damage warrants further investigation.

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Most cited references 37

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Heterogeneity in radiation-induced DNA damage and repair in tumor and normal cells measured using the "comet" assay.

P Olive, Sarah Durand, J Banáth (1990)

A method for measuring DNA damage to individual cells, based on the technique of microelectrophoresis, was described by Ostling and Johanson in 1984 (Biochem. Biophys. Res. Commun. 123, 291-298). Cells embedded in agarose are lysed, subjected briefly to an electric field, stained with a fluorescent DNA-binding stain, and viewed using a fluorescence microscope. Broken DNA migrates farther in the electric field, and the cell then resembles a "comet" with a brightly fluorescent head and a tail region which increases as damage increases. We have used video image analysis to define appropriate "features" of the comet as a measure of DNA damage, and have quantified damage and repair by ionizing radiation. The assay was optimized for lysing solution, lysing time, electrophoresis time, and propidium iodide concentration using Chinese hamster V79 cells. To assess heterogeneity of response of normal versus malignant cells, damage to both tumor cells and normal cells within mouse SCC-VII tumors was assessed. Tumor cells were separated from macrophages using a cell-sorting method based on differential binding of FITC-conjugated goat anti-mouse IgG. The "tail moment", the product of the amount of DNA in the tail and the mean distance of migration in the tail, was the most informative feature of the comet image. Tumor and normal cells showed significant heterogeneity in damage produced by ionizing radiation, although the average amount of damage increased linearly with dose (0-15 Gy) and suggested similar net radiosensitivities for the two cell types. Similarly, DNA repair rate was not significantly different for tumor and normal cells, and most of the cells had repaired the damage by 30 min following exposure to 15 Gy. The heterogeneity in response did not appear to be a result of differences in response through the cell cycle.

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On the possible origins of DNA damage in human spermatozoa.

N. De Groot, R. Alan Aitken (2009)

DNA damage in the male germ line has been linked with a variety of adverse clinical outcomes including impaired fertility, an increased incidence of miscarriage and an enhanced risk of disease in the offspring. The origins of this DNA damage could, in principle, involve: (i) abortive apoptosis initiated post meiotically when the ability to drive this process to completion is in decline (ii) unresolved strand breaks created during spermiogenesis to relieve the torsional stresses associated with chromatin remodelling and (iii) oxidative stress. In this article, we present a two-step hypothesis for the origins of DNA damage in human spermatozoa that highlights the significance of oxidative stress acting on vulnerable, poorly protaminated cells generated as a result of defective spermiogenesis. We further propose that these defective cells are characterized by several hallmarks of 'dysmaturity' including the retention of excess residual cytoplasm, persistent nuclear histones, poor zona binding and disrupted chaperone content. The oxidative stress experienced by these cells may originate from infiltrating leukocytes or, possibly, the entry of spermatozoa into an apoptosis-like cascade characterized by the mitochondrial generation of reactive oxygen species. This oxidative stress may be exacerbated by a decline in local antioxidant protection, particularly during epididymal maturation. Finally, if oxidative stress is a major cause of sperm DNA damage then antioxidants should have an important therapeutic role to play in the clinical management of male infertility. Carefully controlled studies are now needed to critically examine this possibility.

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Safety assessment of esters of p-hydroxybenzoic acid (parabens).

Bakul Soni, Ioana Carabin, George A Burdock (2005)

Parabens are widely used as preservatives in food, cosmetic and pharmaceutical products. Acute, subchronic, and chronic studies in rodents indicate that parabens are practically non-toxic. Parabens are rapidly absorbed, metabolized, and excreted. In individuals with normal skin, parabens are, for the most part, non-irritating and non-sensitizing. However, application of compounds containing parabens to damaged or broken skin has resulted in sensitization. Genotoxicity testing of parabens in a variety of in vitro and in vivo studies primarily gave negative results. The paraben structure is not indicative of carcinogenic potential, and experimental studies support these observations. Some animal studies have reported adverse reproductive effects of parabens. In an uterotrophic assay, methyl and butyl paraben administered orally to immature rats were inactive, while subcutaneous administration of butyl paraben produced a weak positive response. The ability of parabens to transactivate the estrogen receptor in vitro increases with alkyl group size. The detection of parabens in a small number of breast tumor tissue samples and adverse reproductive effects of parabens in animals has provoked controversy over the continued use of these substances. However, the possible estrogenic hazard of parabens on the basis of the available studies is equivocal, and fails to consider the metabolism and elimination rates of parabens, which are dose, route, and species dependent. In light of the recent controversy over the estrogenic potential of parabens, conduct of a reproductive toxicity study may be warranted.

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Author and article information

Journal

Journal ID (nlm-ta): Environ Health Perspect

Title: Environmental Health Perspectives

Publisher: National Institute of Environmental Health Sciences

ISSN (Print): 0091-6765

ISSN (Electronic): 1552-9924

Publication date (Print): February 2011

Publication date (Electronic): 28 September 2010

Volume: 119

Issue: 2

Pages: 252-257

Affiliations

[1 ] Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA

[2 ] Centers for Disease and Control and Prevention, Atlanta, Georgia, USA

[3 ] Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA

[4 ] Vincent Memorial Obstetrics and Gynecology Service, Massachusetts General Hospital, Boston, Massachusetts, USA

Author notes

Address correspondence to J. Meeker, Department of Environmental Health Sciences, University of Michigan School of Public Health, 6635 SPH Tower, 109 S. Observatory St., Ann Arbor, MI 48109 USA. Telephone: (734) 764-7184. Fax: (734) 936-7283. E-mail: meekerj@ 123456umich.edu

The authors declare they have no actual or potential competing financial interests.

Article

Publisher ID: ehp-119-252

DOI: 10.1289/ehp.1002238

PMC ID: 3040614

PubMed ID: 20876036

SO-VID: a39e33c2-0304-4ce6-a1df-ec5de1fe3b4c

Copyright © 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.

Urinary Concentrations of Parabens and Serum Hormone Levels, Semen Quality Parameters, and Sperm DNA Damage

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Most cited references 37

Heterogeneity in radiation-induced DNA damage and repair in tumor and normal cells measured using the "comet" assay.

On the possible origins of DNA damage in human spermatozoa.

Safety assessment of esters of p-hydroxybenzoic acid (parabens).

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