Semen phthalate metabolites, semen quality parameters and serum reproductive hormones: A cross-sectional study in China.

Exposure to phthalates has been found to have adverse effects on male reproductive function in animals. However, the findings from human studies are inconsistent. Here we examined the associations of phthalate exposure with semen quality and reproductive hormones in a Chinese population using phthalate metabolite concentrations measured in semen as biomarkers. Semen (n = 687) and blood samples (n = 342) were collected from the male partners of sub-fertile couples who presented to the Reproductive Center of Tongji Hospital in Wuhan, China. Semen quality parameters and serum reproductive hormone levels were determined. Semen concentrations of 8 phthalate metabolites were assessed using high-performance liquid chromatography and tandem mass spectrometry. Associations of the semen phthalate metabolites with semen quality parameters and serum reproductive hormones were assessed using confounder-adjusted linear and logistic regression models. Semen phthalate metabolites were significantly associated with decreases in semen volume [mono-n-butyl phthalate (MBP), mono-(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)], sperm curvilinear velocity [monobenzyl phthalate (MBzP), MEHP, the percentage of di-(2-ethylhexyl)-phthalate metabolites excreted as MEHP (%MEHP)], and straight-line velocity (MBzP, MEHP, %MEHP), and also associated with an increased percentage of abnormal heads and tails (MBzP) (all p for trend <0.05). These associations remained suggestive or significant after adjustment for multiple testing. There were no significant associations between semen phthalate metabolites and serum reproductive hormones. Our findings suggest that environmental exposure to phthalates may impair human semen quality.

Wang YX ，Zeng Q ，Sun Y ，Yang P ，Wang P ，Li J ，Huang Z ，You L ，Huang YH ，Wang C ，Li YF ，Lu WQ ... -  《-》

Semen quality and insulin-like factor 3: Associations with urinary and seminal levels of phthalate metabolites in adult males.

Certain phthalates have adverse effects on male reproductive functions in animals, and potentially affect human testicular function and spermatogenesis, but little is known about the active mechanisms. We measured the urinary and seminal phthalate metabolites and explored their associations on insulin-like factor 3 (INSL3) and semen quality. Urine, blood, and semen samples were collected from the male partners of subfertile (n = 253) and fertile (n = 37) couples in a reproductive center in southern Taiwan. INSL3, reproductive hormones, semen-quality, and 11 phthalate metabolites in urine and semen were measured. There were significant correlations in the distribution pattern of metabolites, such as the relative contribution of low or high molecular weight phthalate metabolites. The significantly monotonic trends in semen volume, sperm concentration and motility were associated with increasing quartiles of INSL3 (all p-trend < 0.001). In adjusted regression models, increases in urinary phthalate metabolites levels were adversely associated with sperm concentration (monobenzyl phthalate [MBzP], mono-2-ethylhexyl phthalate [MEHP] and MEHP%), motility (MBzP and MEHP) and INSL3 (MBzP, MEHP and MEHP%) (all p < 0.01). Higher seminal phthalate metabolite levels were associated with decreases in sperm concentration (MEHP and mono-2-ethyl-5-hydroxyhexyl phthalate), motility (mono-ethyl phthalate [MEP] and di-(2-ethylhexyl) phthalate [DEHP] metabolites), normal morphology (MEP), and INSL3 (monomethyl phthalate and MEP) (all p < 0.05). Our data suggest that INSL3 secretion, reproductive hormone balance, and sperm production and quality might be simultaneously adversely affected for individuals excreting increasing levels of phthalates metabolites (especially di-ethyl phthalate, butylbenzyl phthalate, and DEHP) in urine and semen samples.

Chang WH ，Wu MH ，Pan HA ，Guo PL ，Lee CC ... -  《-》

Phthalates exposure of Chinese reproductive age couples and its effect on male semen quality, a primary study.

Phthalates are suspected of having adverse effects on androgen-regulated reproductive development in animals and may be toxic for human sperm. The purposes of our study were to investigate the general exposure of a Chinese reproductive age cohort to these ubiquitous pollutants and to assess their potential effect on semen quality. Six phthalate metabolites, monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP), and mono-2-ethyl-5-oxohexyl phthalate (MEOHP) were measured in spot urines of 150 individuals recruited from a Chongqing, China, reproductive institute. The questionnaire and clinical data were evaluated, and the correlations of phthalate exposure and semen qualities like semen volume, sperm concentration, motility and sperm motion parameters, were determined by multiple logistic regression analysis. The creatinine adjusted average concentrations for MMP, MEP, MBP, MBzP, MEHP and MEOHP were 41.3, 300, 41.0, 0.78, 2.99 and 3.90 μg/g, respectively. After adjustment for age, body mass index (BMI), abstinence, smoking, drinking, and education, there was a borderline-significant dose-response relationship between MBP and sperm concentration, with odd ratios (ORs) 1.0, 6.8 and 12.0 for increasing exposure tertiles (p=0.05). Although the dose-response relationships for MMP and MEP versus sperm concentration were not significant, a significant positive correlation between MEP and straight-line velocity of sperm motion was observed. The present data may imply some effects of phthalate exposure on semen. However, due to the small sample size, our finding needs to be confirmed on a larger population.

Liu L ，Bao H ，Liu F ，Zhang J ，Shen H ... -  《-》

Biomonitoring of phthalate metabolites in the Canadian population through the Canadian Health Measures Survey (2007-2009).

Human exposure to phthalates occurs through multiple sources and pathways. In the Canadian Health Measures Survey 2007-2009, 11 phthalate metabolites, namely, MMP, MEP, MnBP, MBzP, MCHP, MCPP, MEHP, MEOHP, MEHHP, MnOP, and MiNP were measured in urine samples of 6-49 year old survey respondents (n=3236). The phthalate metabolites biomonitoring data from this nationally-representative Canadian survey are presented here. The metabolites MEP, MnBP, MBzP, MCPP, MEHP, MEOHP and MEHHP were detected in >90% of Canadians while MMP, MCHP, MnOP and MiNP were detected in <20% of the Canadian population. Step-wise regression analyses were carried out to identify important predictors of volumetric concentrations (μg/L) of the metabolites in the general population. Individual multiple regression models with covariates age, sex, creatinine, fasting status, and the interaction terms age×creatinine, age×sex and fasting status×creatinine were constructed for MEP, MnBP, MBzP, MCPP, MEHP, MEOHP and MEHHP. The least square geometric mean (LSGM) estimates for volumetric concentration (μg/L) of the metabolites derived from respective regression models were used to assess the patterns in the metabolite concentrations among population sub-groups. The results indicate that children had significantly higher urinary concentrations of MnBP, MBzP, MEHP, MEHHP, MEOHP and MCPP than adolescents and adults. Moreover, MEP, MBzP, MnBP and MEOHP concentrations in females were significantly higher than in males. We observed that fasting status significantly affects the concentrations of MEHP, MEHHP, MEOHP, and MCPP metabolites analyzed in this study. Moreover, our results indicate that the sampling time could affect the DEHP metabolite concentrations in the general Canadian population.

Saravanabhavan G ，Guay M ，Langlois É ，Giroux S ，Murray J ，Haines D ... -  《-》

Phthalate exposure and semen quality in fertile US men.

Several experimental and observational studies have demonstrated the antiandrogenicity of several phthalates. However, there is limited evidence of an association between phthalate exposure in adult life and semen quality. The aim of this study was to examine phthalate exposure during adulthood in relation to semen quality in fertile US men. This multi-center cross-sectional study included 420 partners of pregnant women who attended a prenatal clinic in one of five US cities during 1999-2001. Nine phthalate metabolites [mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP)], as well as mono-n-butyl phthalate (MBP) and mono-isobutyl phthalate (MiBP), mono (three carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP), and monoethyl phthalate (MEP)] were measured in urine collected at the same time as the semen sample. We regressed natural log-transformed (ln) sperm concentration, ln(total sperm count), ln(total motile sperm count), percent motile spermatozoa, and percent spermatozoa with normal morphology on each of the nine natural log-transformed metabolite concentrations and on the molar-weighted sum of DEHP metabolites in separate models. We fit unadjusted models and models that adjusted for confounders determined a priori. In unadjusted models, ln(MiBP) was significantly and positively associated with motility and ln(MBzP) significantly negatively associated with ln(total sperm count). In adjusted linear models, urinary metabolite concentrations of DEHP, DBP, DEP, and DOP were not associated with any semen parameter. We found an inverse association between ln(MBzP) concentrations and sperm motility (β = -1.47, 95% CI: -2.61, -0.33), adjusted for ln(creatinine concentration), geographic location, age, race, smoking status, stress, recent fever, time from sample collection and time to complete analysis. Several sensitivity analyses confirmed the robustness of these associations. This study and the available literature suggest that impacts of adult exposure to phthalates at environmental levels on classical sperm parameters are likely to be small.

Thurston SW ，Mendiola J ，Bellamy AR ，Levine H ，Wang C ，Sparks A ，Redmon JB ，Drobnis EZ ，Swan SH ... -  《-》