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

Wang, Yixin; You, Long; Zeng, Qiang; Sun, Yang; Huang, Yue-Hui; Wang, Cheng; Wang, Peng; Cao, Wencheng; Pan, Yang; Li, Yufeng; Lu, Wen-Qing

doi:10.1016/j.envres.2015.06.010

Cited by 129 publications

(58 citation statements)

References 40 publications

(54 reference statements)

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“…MBP, MiBP, MEP, MMP, MEOHP and MBzP) were negatively associated with semen parameters (e.g. sperm concentration, total sperm count and sperm morphology), which was consistent with the results of previous studies (Bloom et al, 2015;Duty et al, 2003;Hauser et al, 2006;Liu et al, 2012;Specht et al, 2014;Wang et al, 2015a). Although we still do not know if DNA methylation or hydroxymethylation play any specific role in the effect of phthalates on spermatogenesis, the mediation analysis in our study showed a statistically suggestive effect (p = 0.06) of phthalate exposure on sperm morphology mediated by urinary 5mdC (SI Table S8).…”

Section: Discussionsupporting

confidence: 92%

“…Urinary metabolites of phthalates have been widely detected in different human populations Guo et al, 2011;Joensen et al, 2012). Human epidemiologic studies have reported associations between exposure to some phthalates and adverse male reproductive outcomes, including reduced sperm quality, increased sperm DNA damage, and altered serum hormone levels, although these associations are not entirely consistent (Bloom et al, 2015;Duty et al, 2003;Hauser et al, 2006;Hauser et al, 2007;Lenters et al, 2015;Joensen et al, 2012;Mendiola et al, 2012;Specht et al, 2014;Thurston et al, 2015;Wang et al, 2015aWang et al, , 2015b. In one animal exposure study, anti-androgenic effects on male reproductive development, decreased testes and epididymis weight, and increased incidences of external reproductive tract malformation in male rats were observed (Saillenfait et al, 2008).…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Associations of urinary 5-methyl-2′-deoxycytidine and 5-hydroxymethyl-2′-deoxycytidine with phthalate exposure and semen quality in 562 Chinese adult men

Pan

Jing

Yeung

et al. 2016

Environment International

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 98%

Associations of urinary 5-methyl-2′-deoxycytidine and 5-hydroxymethyl-2′-deoxycytidine with phthalate exposure and semen quality in 562 Chinese adult men

Pan

Jing

Yeung

et al. 2016

Environment International

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“…Epidemiologic data suggest that exposure to some phthalates is adversely associated with a variety of reproductive outcomes including lower oocyte yield and lower proportion of cycles resulting in pregnancy as well as live birth (Hauser et al, 2015), poor sperm quality measures in the general population (Bloom et al, 2015b) as well as those seeking fertility treatment (Duty et al, 2003; Hauser et al, 2006; Wang et al, 2015), and longer time to pregnancy (Buck Louis et al, 2014). The direct mechanisms by which phthalates may induce these adverse reproductive outcomes are not clear but there is growing evidence that oxidative stress may be a contributing factor.…”

Section: Introductionmentioning

confidence: 99%

Urinary phthalate and phthalate alternative metabolites and isoprostane among couples undergoing fertility treatment

Olmsted

Cantonwine

et al. 2017

Environmental Research

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Background Epidemiological data suggest associations between phthalate exposures to a variety of adverse reproductive outcomes including reduced sperm quality and reproductive success. While mechanisms of these associations are not fully elucidated, oxidative stress has been implicated as a potential mediator. We examined associations of urinary metabolites of phthalates and phthalate alternative plasticizers with oxidative stress among couples seeking fertility treatment. Methods Seventeen urinary plasticizer metabolites and 15-F2t isoprostane, a biomarker of oxidative stress, were quantified in spot samples from 50 couples seeking fertility treatment who enrolled in the Sperm Environmental Epigenetics and Development Study during 2014-2015. Results In multivariable analyses, percent change in isoprostane was positively associated with interquartile range increases for the oxidative metabolites of di-2-ethylhexyl phthalate, [mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP; 20.0%, p=0.02), mono-2-ethyl-5-oxohexyl phthalate (MEOHP; 24.1%, p=0.01), and mono-2-ethyl-5-carboxypentyl phthalate (MECPP; 24.1%, p=0.004)], mono-isobutyl phthalate (MiBP; 17.8%, p=0.02), mono-hydroxyisobutyl phthalate (MHiBP; 27.5%, p=0.003), and cyclohexane-1,2-dicarboxylic acid mono-hydroxy-isononyl ester (MHINCH; 32.3%, p=0.002). Stratification of participants by sex revealed that isoprostane was positively associated with MHiBP (41.4%, p=0.01) and monocarboxy-isononyl phthalate (MCNP; 26.0%, p=0.02) among females and MEOHP (35.8%, p=0.03), MiBP (29.2%, p=0.01), MHiBP (34.7%, p=0.007) and MHINCH (49.0%, p=0.002) among males. Conclusions Our results suggest that exposure to phthalates and phthalate replacements are associated with higher levels of oxidative stress in a sex-specific manner. Additional studies are needed to replicate our findings and to examine the potential health implications of the use of phthalates and alternative phthalates in consumer end products.

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“…There are several epidemiologic studies in adult men that explored cross-sectional associations between background low-DBP environmental exposure, and other phthalates, with semen quality. Most of these studies were conducted in men recruited from infertility clinics 20-27 , and although some studies found associations of DBP 22,24 and other phthalates 20,21,24,25,28 with lower semen quality, others did not 23,29,30 .…”

Section: Introductionmentioning

confidence: 99%

A crossover–crossback prospective study of dibutyl-phthalate exposure from mesalamine medications and semen quality in men with inflammatory bowel disease

Nassan

Coull

Skakkebæk

et al. 2016

Environment International

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Background Phthalates are widely used chemicals with ubiquitous exposure. Dibutyl-phthalate (DBP), a male reproductive toxicant in animals, is understudied in humans. Some mesalamine medications used to treat inflammatory bowel disease (IBD) have DBP in their coating, whereas other mesalamine formulations do not. Objectives Taking advantage of differences in mesalamine formulations, we investigated whether high-DBP exposure from mesalamine medications was associated with decreased semen parameters. Methods 73 men with IBD taking mesalamine participated in a crossover-crossback prospective study. Men taking non-DBP containing mesalamine at baseline i.e., background exposure, crossed-over for four months to high-DBP mesalamine and then crossed-back for four months to their non-DBP mesalamine (B1HB2-arm;Background1-High-Background2) and vice versa for men taking high-DBP mesalamine at baseline (H1BH2-arm;High1-Background-High2). Men provided up to six semen samples (2: baseline, 2: crossover and 2: crossback). Results We estimated crossover, crossback and carryover effects using linear mixed models adjusted for abstinence time, age, season and duration on high-DBP mesalamine at baseline. Semen parameters in B1HB2-arm (26 men, 133 samples) decreased after high-DBP mesalamine exposure (crossover versus baseline), especially motility parameters, and continued to decrease further even after crossback to non-DBP mesalamine (crossback versus crossover).The cumulative carryover effect of high-DBP (crossback versus baseline) was a decrease of % total sperm motility by 7.61(CI:-13.1, -2.15), % progressive sperm motility by 4.23(CI:-8.05, -0.4) and motile sperm count by 26.0% (CI:-46.2%, 1.7%). However, H1BH2-arm (47 men, 199 samples) had no significant change during crossover or crossback. Conclusions Men newly exposed to high-DBP mesalamine for four months had a cumulative reduction in several semen parameters, primarily sperm motility, that was more pronounced and statistically significant even after exposure ended for four months.

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

Cited by 129 publications

References 40 publications

Associations of urinary 5-methyl-2′-deoxycytidine and 5-hydroxymethyl-2′-deoxycytidine with phthalate exposure and semen quality in 562 Chinese adult men

Associations of urinary 5-methyl-2′-deoxycytidine and 5-hydroxymethyl-2′-deoxycytidine with phthalate exposure and semen quality in 562 Chinese adult men

Urinary phthalate and phthalate alternative metabolites and isoprostane among couples undergoing fertility treatment

A crossover–crossback prospective study of dibutyl-phthalate exposure from mesalamine medications and semen quality in men with inflammatory bowel disease

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