Phthalate exposure and human semen quality: Results from an infertility clinic in China.

Exposure to phthalates has been demonstrated to have adverse effects on male reproduction in animal studies, but findings in human studies have been inconsistent. We recruited 1040 men from the Reproductive Center of Tongji Hospital in Wuhan, China from March to June 2013. Each man provided one semen sample and two urine samples. Semen quality parameters and the urinary concentrations of eight phthalate metabolites were determined. After multivariable adjustments, the urinary concentrations of monobutyl phthalate (MBP) were found to be positively associated with the below-reference sperm concentration and total sperm count, and the odds ratios (ORs) comparing extreme MBP quartiles were 2.01 (95% CI: 1.07, 3.79; p for trend=0.06) and 1.80 (95% CI: 1.05, 3.08; p for trend=0.02), respectively. The associations were confirmed by multivariable linear regression analysis, which showed that the MBP concentration was significantly associated with decreasing trends in the sperm concentration and total sperm count (both p for trend <0.05). Additionally, we found significant dose-dependent relationships of the urinary level of mono-(2-ethylhexyl) phthalate (MEHP) and the percentage of di-(2-ethylhexyl)-phthalate metabolites (DEHP) excreted as MEHP (%MEHP) with an increased percentage of abnormal heads (both p for trend <0.01). Our findings suggest that environmental exposure to di-n-butyl phthalate (DBP) and DEHP may contribute to a decline in semen quality.

[1]  J. Furr,et al.  Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[2]  Antonia M. Calafat,et al.  Temporal Variability of Urinary Phthalate Metabolite Levels in Men of Reproductive Age , 2004, Environmental health perspectives.

[3]  P. Foster,et al.  Effects of phthalate esters on the developing reproductive tract of male rats , 2001, Human reproduction update.

[4]  N Keiding,et al.  Evidence for decreasing quality of semen during past 50 years. , 1992, BMJ.

[5]  S. Yoshimura,et al.  Effect of butyl benzyl phthalate in Sprague-Dawley rats after gavage administration: a two-generation reproductive study. , 2000, Reproductive toxicology.

[6]  J. Daurès,et al.  Prenatal environmental risk factors for genital malformations in a population of 1442 French male newborns: a nested case-control study. , 2011, Human reproduction.

[7]  N. Pant,et al.  Correlation of phthalate exposures with semen quality. , 2008, Toxicology and applied pharmacology.

[8]  Robert F. Herrick,et al.  Phthalate Exposure and Human Semen Parameters , 2003, Epidemiology.

[9]  R. Maronpot,et al.  Adverse effects of butyl benzyl phthalate on the reproductive and hematopoietic systems of male rats. , 1985, Toxicology.

[10]  L. Hagmar,et al.  Urinary Phthalate Metabolites and Biomarkers of Reproductive Function in Young Men , 2005, Epidemiology.

[11]  U. N. Joensen,et al.  Phthalate Excretion Pattern and Testicular Function: A Study of 881 Healthy Danish Men , 2012, Environmental health perspectives.

[12]  Jia Cao,et al.  Urinary phthalate metabolites and male reproductive function parameters in Chongqing general population, China. , 2014, International journal of hygiene and environmental health.

[13]  J. Brock,et al.  The relationship between environmental exposure to phthalates and computer-aided sperm analysis motion parameters. , 2004, Journal of andrology.

[14]  M. Baras,et al.  CHANGES IN SEMEN QUALITY IN JERUSALEM BETWEEN 1990 AND 2000: A CROSS-SECTIONAL AND LONGITUDINAL STUDY , 2003, Archives of andrology.

[15]  Ken Takahashi,et al.  Decreased Serum Free Testosterone in Workers Exposed to High Levels of Di-n-butyl Phthalate (DBP) and Di-2-ethylhexyl Phthalate (DEHP): A Cross-Sectional Study in China , 2006, Environmental health perspectives.

[16]  R. Mclachlan,et al.  Testosterone effects on spermatogenesis in the gonadotropin-releasing hormone-immunized rat. , 1994, Biology of reproduction.

[17]  B. Le Bizec,et al.  Human testis steroidogenesis is inhibited by phthalates. , 2012, Human reproduction.

[18]  Tingting Ma,et al.  Phthalate esters contamination in soils and vegetables of plastic film greenhouses of suburb Nanjing, China and the potential human health risk , 2015, Environmental Science and Pollution Research.

[19]  Yu-bang Wang,et al.  Effects of di-n-butyl phthalate on male rat reproduction following pubertal exposure. , 2011, Asian journal of andrology.

[20]  Yankai Xia,et al.  Association of exposure to phenols and idiopathic male infertility. , 2013, Journal of hazardous materials.

[21]  R. Mclachlan,et al.  Testosterone withdrawal promotes stage-specific detachment of round spermatids from the rat seminiferous epithelium. , 1996, Biology of reproduction.

[22]  Antonia M. Calafat,et al.  Variability over 1 Week in the Urinary Concentrations of Metabolites of Diethyl Phthalate and Di(2-Ethylhexyl) Phthalate among Eight Adults: An Observational Study , 2010, Environmental health perspectives.

[23]  C. Niederberger.  Re: Association of exposure to phenols and idiopathic male infertility. , 2013, The Journal of urology.

[24]  W. Hanke,et al.  Human urinary phthalate metabolites level and main semen parameters, sperm chromatin structure, sperm aneuploidy and reproductive hormones. , 2013, Reproductive toxicology.

[25]  M. Perrot-Applanat,et al.  Xenoestrogens modulate vascular endothelial growth factor secretion in breast cancer cells through an estrogen receptor-dependent mechanism. , 2008, The Journal of endocrinology.

[26]  J. Sumpter,et al.  A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic. , 1995, Environmental health perspectives.

[27]  A. Calafat,et al.  Altered Semen Quality in Relation to Urinary Concentrations of Phthalate Monoester and Oxidative Metabolites , 2006, Epidemiology.

[28]  J. Arnaud,et al.  Reproductive toxicity of di(2-ethylhexyl) phthalate in selenium-supplemented and selenium-deficient rats , 2011, Drug and chemical toxicology.

[29]  Heqing Shen,et al.  Phthalates exposure of Chinese reproductive age couples and its effect on male semen quality, a primary study. , 2012, Environment international.

[30]  Qian Wu,et al.  Phthalate metabolites in urine from China, and implications for human exposures. , 2011, Environment international.

[31]  J. Furr,et al.  A mixture of five phthalate esters inhibits fetal testicular testosterone production in the sprague-dawley rat in a cumulative, dose-additive manner. , 2008, Toxicological sciences : an official journal of the Society of Toxicology.

[32]  S Greenland,et al.  Modeling and variable selection in epidemiologic analysis. , 1989, American journal of public health.

[33]  Yi-Xin Wang,et al.  Semen phthalate metabolites, spermatozoa apoptosis, and DNA damage: a cross-sectional study in China. , 2015, Environmental science & technology.

[34]  Na Li,et al.  Dibutyl phthalate contributes to the thyroid receptor antagonistic activity in drinking water processes. , 2010, Environmental science & technology.

[35]  V. Wagner,et al.  Decline in semen concentration and morphology in a sample of 26,609 men close to general population between 1989 and 2005 in France. , 2013, Human reproduction.

[36]  T. K. Jensen,et al.  Urinary Bisphenol A Levels in Young Men: Association with Reproductive Hormones and Semen Quality , 2014, Environmental health perspectives.

[37]  N. Skakkebaek,et al.  Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects , 2001, Human reproduction.

[38]  J. Auger,et al.  WHO laboratory manual for the examination and processing of human semen , 2010 .

[39]  Soon Young Han,et al.  An Exposure Assessment of DI-(2-Ethylhexyl) Phthalate (DEHP) and DI-n-Butyl Phthalate (DBP) in Human Semen , 2009, Journal of toxicology and environmental health. Part A.

[40]  C. A. Harris,et al.  The estrogenic activity of phthalate esters in vitro. , 1997, Environmental health perspectives.