Human urinary/seminal phthalates or their metabolite levels and semen quality: A meta-analysis

Cai, Hongquan; Zheng, Weiwei; Zheng, Pai; Shu, Wang; Tan, Handong; He, Gengsheng; Qu, Weidong

doi:10.1016/j.envres.2015.07.008

Cited by 60 publications

(34 citation statements)

References 51 publications

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“…In similar potentially infertile male populations, Jurewicz and collaborators (2013) and Pant and coworkers (2014) showed an inverse association between urinary DEHP metabolites and sperm motility. Finally, in a recent meta-analysis (14 studies) looking at the associations between phthalates or their metabolite levels and human semen quality, Cai and colleagues (2015) found some evidence of an inverse relationship between specific phthalate exposures and impaired semen quality (e.g. MBP, MBzP or MEHP), but also noted that there were several cases where associations between phthalates and semen quality were not found (e.g.…”

Section: Discussionmentioning

confidence: 99%

Phthalate exposure and semen quality in fertile US men

et al. 2015

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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 U.S. 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 (3 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 sperm and percent sperm 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.

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Section: Discussionmentioning

confidence: 99%

Phthalate exposure and semen quality in fertile US men

et al. 2015

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“…Phthalate exposure in humans has been associated with a number of adverse health outcomes, including asthma, inflammation, poorer birth outcomes, child growth, and sperm quality (Cai et al, 2015; Ferguson et al, 2015; Smarr et al, 2015; Teitelbaum et al, 2012; Whyatt et al, 2014). Several studies have identified adverse effects particularly in response to phthalate exposure during pregnancy (Kim et al, 2011; Valvi et al, 2015a; Whyatt et al, 2014), suggesting that the in utero period may be a critical window of vulnerability.…”

Section: Introductionmentioning

confidence: 99%

Maternal phthalate exposure during pregnancy is associated with DNA methylation of LINE-1 and Alu repetitive elements in Mexican-American children

Huen

Calafat

Bradman

et al. 2016

Environmental Research

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Phthalates are frequently used in personal care products and plasticizers and phthalate exposure is ubiquitous in the US population. Exposure to phthalates during critical periods in utero has been associated with a variety of adverse health outcomes but the biological mechanisms linking these exposures with disease are not well characterized. In this study, we examined the relationship of in utero phthalate exposure with repetitive element DNA methylation, an epigenetic marker of genome instability, in children from the longitudinal birth cohort CHAMACOS. Methylation of Alu and long interspersed nucleotide elements (LINE-1) was determined using pyrosequencing of bisulfite-treated DNA isolated from whole blood samples collected from newborns and 9 year old children (n=355). Concentrations of eleven phthalate metabolites were measured in urine collected from pregnant mothers at 13 and 26 weeks gestation. We found a consistent inverse association between prenatal concentrations of monoethyl phthalate, the most frequently detected urinary metabolite, with cord blood methylation of Alu repeats (β(95%CI):−0.14(−0.28,0.00) and −0.16(−0.31,−0.02)) for early and late pregnancy, respectively, and a similar but weaker association with LINE-1 methylation. Additionally, increases in urinary concentrations of di-(2-ethylhexyl) phthalate metabolites during late pregnancy were associated with lower levels of methylation of Alu repeats in 9 year old blood (significant p-values ranged from 0.003 to 0.03). Our findings suggest that prenatal exposure to some phthalates may influence differences in repetitive element methylation, highlighting epigenetics as a plausible biological mechanism through which phthalates may affect health.

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“…Phthalate exposure is widespread, such that urinary phthalate metabolites have been detected in the majority of individuals from representative samples within the U.S. general population (CDC, 2010). In humans, urinary phthalate metabolite concentrations have been associated with adverse male reproductive outcomes such as shorter anogenital distance (Suzuki et al, 2012; Swan et al, 2015), abnormal sex steroid hormone synthesis (Meeker et al, 2009), lower serum testosterone (Meeker and Ferguson, 2014), reduced sperm motility, concentration (Cai et al, 2015; Pant et al, 2014), and increased DNA damage (Hauser et al, 2007). Additionally, studies of phthalate exposure animal models reported reduced sex organ weight (Shono and Taguchi, 2014), abnormal Leydig cell aggregation (Mahood et al, 2007), repression of sex determination (Wang et al, 2016), altered sex ratio (Dobrzynska et al, 2011), and delayed sexual maturity (Lee et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Associations of urinary phthalate metabolites and lipid peroxidation with sperm mitochondrial DNA copy number and deletions

Huffman

Rosati

et al. 2018

Environmental Research

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Background: Phthalates, a chemical class of plasticizers, are ubiquitous environmental contaminants that have been associated with oxidative stress. Mitochondria DNA copy number (mtDNAcn) and DNA deletions (mtDNAdel) are emerging biomarkers for cellular oxidative stress and environment exposures. Objectives: To examine associations of urinary phthalate metabolite and isoprostane concentrations on sperm mtDNAcn and mtDNAdel in male partners undergoing assisted reproductive technologies (ART). Methods: Ninety-nine sperm samples were collected from male partners undergoing ART at Baystate Medical Center in Springfield, MA as part of the Sperm Environmental Epigenetics and Development Study (SEEDS). Seventeen urinary phthalate metabolite concentrations were analyzed by the Centers for Disease Control using tandem mass spectrometry. Urinary 15-F2t-isoprostane concentrations, a biomarker of lipid peroxidation, were measured using a competitive enzyme-linked immunosorbent assay. A triplex qPCR method was used to determine the relative quantification of mtDNAcn and mtDNAdel. Results: Sperm mtDNAcn and mtDNAdel were positively correlated (Spearman rho = 0.31; p = .002). Adjusting for age, BMI, current smoking, race, and measurement batch, urinary monocarboxy-isononyl phthalate (MCNP) concentrations were positively associated with mtDNAcn (β = 1.63, 95% CI: 0.14, 3.11). Other urinary phthalate metabolite and isoprostane concentrations were not associated with sperm mtDNAcn or mtDNAdel. Conclusions: Among this cohort of male ART participants, those with higher MCNP had higher mtDNAcn; other phthalate metabolites and isoprostane were not associated with mtDNAcn and mtDNAdel. Given our relatively small sample size, our results should be interpreted with caution. Future research is needed to replicate the findings in larger studies and among sperm samples obtained from the general population.

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Human urinary/seminal phthalates or their metabolite levels and semen quality: A meta-analysis

Cited by 60 publications

References 51 publications

Phthalate exposure and semen quality in fertile US men

Phthalate exposure and semen quality in fertile US men

Maternal phthalate exposure during pregnancy is associated with DNA methylation of LINE-1 and Alu repetitive elements in Mexican-American children

Associations of urinary phthalate metabolites and lipid peroxidation with sperm mitochondrial DNA copy number and deletions

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