A Pilot Study Associating Urinary Concentrations of Phthalate Metabolites and Semen Quality

Abstract

Phthalates are ubiquitous industrial chemicals that are reported to adversely affect human reproductive outcomes. Divergent effects on semen quality have been reported in a limited number of studies. To assess the possible contribution of regional differences in phthalate exposure to these results, we wished to determine if ambient phthalate exposure of men from the Great Lakes region was associated with human sperm parameters. Male partners (N=45) of subfertile couples presenting to a Michigan infertility clinic were recruited. Urinary concentrations of several phthalate metabolites were measured in these men. Semen parameters, measured according to the World Health Organization [WHO 1999] protocols, were divided into those at or above WHO cutoffs for motility (50% motile), concentration (20 million/mL) and morphology (4% normal) and those below. Phthalate metabolite concentrations were divided into those concentrations above the median and those at or below the median. Specific gravity was used as a covariate in the regression models to adjust for urine dilution. Low sperm concentration was significantly associated with above median concentrations of monoethyl phthalate (MEP) (OR=6.5, 95% CI: 1.0-43.6) and low morphology with above median concentrations of mono-3-carboxypropyl phthalate (OR=7.6, 95% CI: 1.7-33.3). Increased odds for low concentration and above median concentrations of metabolites of di(2-ethylhexyl) phthalate (DEHP) (OR=5.4, 95% CI: 0.9-30.8) and low morphology and above median concentrations of MEP (OR=3.4, 95% CI: 0.9-13.8) were also found. A significant trend was observed for tertiles of MEP and low sperm concentration (p=0.05). Results suggest that ambient phthalate metabolite concentrations may adversely affect human semen quality.

Environmental factors and semen quality

“…They observed an inverse dose-response relationship between 2 phthalate metabolites (monobutyl-and monobenzyl phthalate (MBP, MbzP)) on the one side and sperm concentration and motility on the other. These findings were corroborated in a subsequent study of 463 infertile men using same study design [55] and to some extent by a smaller study including 45 infertility clients from the Great Lakes Region in US [57]. Also in a study performed in India, a negative correlation between semen phthalate…”

“…Other studies in animals showed reduction of protein levels in foetal Leyding cells and deregulation of cholesterol transport and steroid synthesis [52]. Several recent epidemiological studies have addressed the male reproductive toxicity of phthalates [53][54][55][56][57][58][59] (Table 5). Duty et al (2003) [53] compared levels of eight phthalate metabolites in urine among men with normal and abnormal semen quality recruited from 168 subfertile couples.…”

Exposure to phthalates: Reproductive outcome and children health. A review of epidemiological studies

“…There were strong, inverse associations between increasing concentrations of high molecular weight phthalate metabolites [MBzP, mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), in a subsequent study of 463 infertile men using the same study design [15] and to some extent by a smaller study including 45 infertility clinic clients from the Great Lakes Region in US [50]. In line are also results of a study performed in India.…”

“…Several recent epidemiological studies have addressed the male reproductive toxicity of phthalates [14,15,[48][49][50][51][52] (Table 3). Duty et al [48], in Boston compared levels of eight phthalate metabolites in urine among men with normal and abnormal semen quality recruited from 168 subfertile couples.…”

Spermatozoa as biomarkers for the assessment of human male infertility and genotoxicity

“…The reproductive toxicity of phthalates has recently been addressed. An association between body levels of several phthalate metabolites and poor basic semen parameters of sperm concentration, morphology, and motility has been identified [Duty et al 2003;Hauser et al 2006;Wirth et al 2008]. As with PCBs there was no significant effect on DNA integrity as assessed by SCSA as a function of urinary monoethyl phthalate [Jonsson et al 2005].…”