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. 2022 Aug 20;11(8):1617. doi: 10.3390/antiox11081617

Table 1.

Association of endocrine-disrupting chemicals—bisphenols, phthalates, and parabens—with human semen quality and oxidative stress: review of the studies.

Study/Author Year Number of Patients EDC Outcome
BPA
Meeker et al. [51] 2010 190 men at an infertility clinic
  • -

    Urine and semen samples

  • -

    Urinary BPA concentrations

  • -

    Evaluation of semen quality

  • -

    Evaluation of sperm DNA damage (comet tail)
  • -

    Increased urinary BPA concentrations were associated with declines in sperm concentration, motility, and morphology, as well as increased sperm DNA damage
Lassen et al. [52] 2014 308 young Danish men from the general population
  • -

    Urine and semen samples

  • -

    Urinary BPA concentrations measured using isotope dilution TurboFlow liquid chromatography with tandem mass spectrometry

  • -

    Evaluation of sperm quality
  • -

    BPA concentration above the lowest quartile was associated with higher levels of serum T, LH, E2, and free T compared to the lowest quartile

  • -

    Men in the highest quartile of BPA excretion had on average 18% higher total T and 13% higher E2 levels compared with the lowest quartile.

  • -

    Men in the highest quartile of urinary BPA concentrations had a significantly lower percentage of progressive motile spermatozoa compared with men in the lowest quartile
Vitku et al. [53] 2016 191 men with different degrees of (in)fertility from an infertility clinic
  • -

    Blood plasma and seminal plasma

  • -

    Determination of BPA in blood and seminal plasma
  • -

    Seminal BPA, but not plasma BPA, was negatively associated with sperm concentration, count, and morphology
Hu et al. [54] 2017 357 obese men
  • -

    Urine and semen samples

  • -

    Determination of urinary concentrations of BPA

  • -

    Evaluation of semen quality
  • -

    Urinary BPA concentrations were significantly correlated with sperm counts per ejaculate
Omran et al. [55] 2018 100 men: 50 infertile men and 50 control men with normal semen quality
  • -

    Urine and semen samples

  • -

    Determination of urinary concentrations of BPA

  • -

    Evaluation of semen quality

  • -

    Evaluation of antioxidant levels and sperm DNA damage
  • -

    Urinary BPA concentrations were negatively associated with semen quality and antioxidant levels, and positively correlated with DNA damage
Adoamnei et al. [56] 2018 215 healthy men, aged 18–23 years, recruited in southern Spain
  • -

    Urine, semen, and blood samples

  • -

    Determination of urinary BPA concentrations using dispersive liquid–liquid microextraction and ultrahigh-performance liquid chromatography with tandem mass spectrometry detection

  • -

    Evaluation of sperm quality and reproductive hormone levels
  • -

    There was a significant positive association between urinary BPA concentrations and serum LH levels

  • -

    Urinary BPA concentrations were significantly and inversely associated with sperm concentrations and total sperm counts
Caporossi et al. [57] 2020 105 men at an infertility clinic
  • -

    Urine and semen samples

  • -

    Urinary levels of BPA and six phthalate metabolites (MEP, MBzP, MnBP, MEHP, MnOP, and MiNP) were analyzed by high-performance liquid chromatography with tandem mass spectrometry

  • -

    Evaluation of associations between BPA and phthalates and semen quality using regression analysis
  • -

    Semen volume was positively associated with BPA, MnBP, and MnOP levels, while it was negatively associated with MiNP levels

  • -

    Sperm concentration had a significant inverse relationship with MEP levels.

  • -

    Negative association was found between the use of plastic containers for food storage and semen volume

  • -

    Significant positive correlation between the consumption of canned food and the levels of BPA, and between the use of perfumes and levels of MEP
Palak et al. [58] 2021 116 men: 20 infertile men with non-obstructive azoospermia, 46 infertile men with oligoasthenoteratozoospermia, and 50 control normospermic men
  • -

    Semen (seminal plasma) and blood samples

  • -

    Analysis of BPA in seminal plasma

  • -

    Analysis of sperm quality
  • -

    Levels of BPA in the seminal plasma of azoospermic men were significantly higher compared to the healthy controls

  • -

    Concentrations of E2 and A were significantly decreased in the seminal plasma of azoospermic men compared to the normospermic men

  • -

    Levels of BPA were negatively correlated with sperm concentration and normal semen morphology

  • -

    BPA was correlated with the miR-let-7a, miR-let-7c, and miR-518f levels in seminal plasma, suggesting that BPA may act directly in seminal plasma, affecting the testicular environment
Benson et al. [59] 2021 556 young adult Danish men, aged 18–20 years
  • -

    Urine and semen samples

  • -

    Determination of urinary BPA, BPF, and BPS concentrations

  • -

    Evaluation of semen quality:

  • -

    volume, sperm concentration, total sperm count, sperm motility, and sperm morphology

  • -

    Associations between urinary bisphenol levels and semen characteristics were estimated using an adjusted negative binomial regression model
  • -

    No associations between urinary bisphenol concentrations and semen quality were found.
Chen et al. [60] 2022 984 Chinese men from an infertility clinic
  • -

    Urine and semen samples

  • -

    Analyses of urinary concentrations of BPA, BPS, and BPF

  • -

    Urinary measurements were associated with semen quality
  • -

    Higher BPA exposure was associated with increased odds ratios (ORs) of having below-reference sperm concentration, total sperm count, progressive motility, and total motility

  • -

    Higher BPS exposure was associated with increased ORs of having below-reference progressive motility and total motility

  • -

    Higher exposure to individual BPA, BPS, and bisphenol mixtures was associated with impaired semen quality. This was not observed for BPF
Phthalates
Duty et al. [61] 2003 168 men
  • -

    Urine and semen samples

  • -

    Determination of urinary concentrations of eight phthalate metabolites using high-performance liquid chromatography and tandem mass spectrometry

  • -

    Evaluation of sperm DNA integrity using a neutral single-cell microgel electrophoresis assay (comet assay)
  • -

    Statistically significant positive association between urinary MEP and mean comet extent as a measure of DNA fragmentation, e.g., damage

  • -

    No significant associations were found between comet assay parameters and other urinary phthalate metabolites, including MBP, MBzP, MEHP, and MMP
Hauser et al. [62] 2006 463 male partners from subfertile couples
  • -

    Urine and semen samples

  • -

    Determination of urine phthalate metabolites using solid-phase extraction coupled with high-performance liquid chromatography isotope dilution tandem mass spectrometry

  • -

    Evaluation of semen quality
  • -

    Dose–response relationships of MBP with low sperm concentration (odds ratio per quartile adjusted for age, abstinence time, and smoking status) and motility

  • -

    There was suggestive evidence of an association between the highest MBzP quartile and low sperm concentration
Liu et al. [63] 2012 150 Chinese men of reproductive age
  • -

    Urine and semen samples

  • -

    Determination of urinary MBP phthalate concentrations

  • -

    Evaluation of semen quality
  • -

    Increased urinary concentrations of MBP phthalate were associated with decreased sperm concentrations.
Jurewitz et al. [64] 2013 269 men with normal semen concentration or slight oligozoospermia
  • -

    Urine, semen and blood samples

  • -

    Determination of urinary phthalate metabolites

  • -

    Evaluation of semen quality (sperm concentration, motility, morphology, CASA parameters)

  • -

    Evaluation of sperm chromatin structure and sperm aneuploidy

  • -

    Determination of reproductive hormones
  • -
    Higher levels of urinary phthalate metabolites were significantly associated with:
    • ◦
      Decreases in sperm motility (5OH MEHP, MEHP, MINP) and CASA parameters (MBP)
    • ◦
      Decreases in testosterone levels (MEHP)
    • ◦
      Increases in sperm DNA damage (MBP)
    • ◦
      Increases in sperm aneuploidy (MBzP, MBP, MEHP, MEP)
Axelsson et al. [65] 2015 314 young Swedish men from the general population
  • -

    Urine, semen, and blood samples

  • -

    Determination of urinary metabolites of phthalates

  • -

    Determination of reproductive hormones

  • -

    Evaluation of semen and sperm high DNA stainability (HDS)—a marker of sperm immaturity
  • -

    Levels of DEHP metabolites—particularly urinary MECPP—were negatively associated with progressive sperm motility

  • -

    Men in the highest quartile of MECPP concentration had 27% higher HDS than men in the lowest quartile
Bloom et al. [66] 2015 501 men from the United States—male partners in couples discontinuing contraception to become pregnant—general population
  • -

    Urine and semen samples

  • -

    Determination of 14 monoester metabolites of phthalate diesters using high-performance liquid chromatography coupled with tandem mass spectrometry

  • -

    Evaluation of semen quality
  • -
    Increased levels of urinary MCMHP, MEHHP, MBzP, and MNP were significantly associated with:
    • ◦
      Lower total sperm counts and concentrations
    • ◦
      Larger sperm heads
    • ◦
      Higher proportions of megalohead sperm morphology
    • ◦
      Other morphological changes of the spermatozoa
  • -

    Urinary MMP and MCPP were significantly associated with lower sperm motility.

  • -

    Urinary MEHP was significantly associated with higher sperm motility
Wang et al. [67] 2015 1040 Chinese infertile men from an infertility clinic
  • -

    Urine and semen samples

  • -

    Determination of urinary concentrations of eight phthalate metabolites

  • -

    Evaluation of semen quality
  • -

    Urinary concentrations of MBP were found to be positively associated with below-reference sperm concentrations and total sperm counts

  • -

    Significant dose-dependent relationships of the urinary level of MEHP and the percentage of DEHP excreted as MEHP (%MEHP) with an increased percentage of abnormal sperm heads.
Jurewicz et al. [68] 2016 194 men aged less than 45 years, with normal sperm concentration or with slight oligozoospermia
  • -

    Urine and semen samples

  • -

    Urinary phthalate metabolites were analyzed

  • -

    Semen quality was evaluated

  • -

    Sperm chromosome Y:X ratio was assessed by FISH
  • -

    MEHP concentrations were negatively related to Y:X sperm chromosome ratios
Thurston et al. [69] 2016 420 men from the US—fertile partners of pregnant women
  • -

    Urine and semen samples

  • -

    Determination of urinary concentrations of nine phthalate metabolites in urine: MEHP, MEHHP, MEOHP, MECPP, MBP, MiBP, MCPP, MBzP, and MEP

  • -

    Evaluation of semen quality
  • -

    In adjusted linear models, urinary metabolite concentrations were not associated with any semen parameters

  • -

    An inverse association between MBzP concentrations and sperm motility was found
Chen et al. [70] 2017 796 male students who experienced a relocation of campuses and shifting environmental exposure
  • -

    Urine, semen, and blood samples

  • -

    Determination of 13 urinary phthalate metabolites

  • -

    Evaluation of semen quality and reproductive hormones
  • -

    All but two semen/hormone outcomes were associated with at least one phthalate metabolite: Decrease in sperm concentration, total sperm number, and progressive motility
Parabens
Meeker et al. [71] 2011 190 male partners attending an infertility clinic, aged between 18 and 55 years, without post-vasectomy status
  • -

    Urine, semen, and blood samples were collected

  • -

    Urine samples were analyzed for MP, PP, BP, and BPA

  • -

    Associations with serum hormone levels, semen quality parameters, and sperm DNA damage measures were assessed using multivariable linear regression
  • -

    Detection rates in urine were 100% for MP, 92% for PP, and 32% for BP

  • -

    No statistically significant associations were observed between MP or PP and the outcome measures

  • -

    Urinary BP concentrations were not associated with hormone levels or conventional semen quality parameters, but they were positively associated with sperm DNA damage

  • -

    When urinary BPA quartiles were added to the model, BP and BPA were both positively associated with sperm DNA damage

  • -

    Assessment of paraben concentrations in repeated urine samples from a subset of the men (n = 78) revealed substantial temporal variability
Jurewiczet al. [42] 2017 315 men who attended an infertility clinic for diagnostic purposes, with normal semen concentrations
  • -

    Urine, semen, and saliva samples

  • -

    Analysis of five parabens’ concentrations using a validated gas chromatography ion-tap mass spectrometry method
  • -

    Urinary parabens’ concentrations were significantly associated with an increase in the percentage of spermatozoa with abnormal morphology, increased DNA fragmentation, and a decrease in the percentage of motility and serum T levels
Nishihama et al. [72] 2017 42 male partners of couples who visited a gynecology clinic for infertility consultation
  • -

    Urine and semen samples

  • -

    Analyses of urinary parabens: MP, EP, PP, and BP

  • -

    Multiple regression and logistic regression analyses of associations between concentrations of urinary parabens and sperm parameters
  • -

    No significant association was found between semen parameters and urinary paraben concentrations in multiple regression analyses and logistic regression analyses
Adoamnei et al. [73] 2018 Cross-sectional study with 215 young university students (18–23 years old) recruited in southern Spain
  • -

    Urine, blood, and semen samples retrieved on a single day

  • -

    Urinary paraben concentrations were measured

  • -

    Reproductive hormones (FSH, T, E2, inhibin B) were measured in serum samples

  • -

    Semen quality was evaluated
  • -

    Ninety-four percent of men had detectable urinary concentrations of parabens

  • -

    Urinary concentrations of parabens or their molar sum were not significantly associated with any semen parameters or reproductive hormone levels
Smarr et al. [74] 2018 501 male partners of couples planning to become pregnant
  • -

    Urine and semen samples

  • -

    Urinary paraben concentrations were measured

  • -

    Linear adjusted mixed-effects models were used for analysis of semen parameters
  • -

    Parabens were associated with diminished sperm count and several sperm motility parameters

  • -

    Hydroxylated paraben metabolites were significantly positively associated with selected semen quality parameters

Abbreviations: A, androstenedione; BP, butyl paraben; BPA, bisphenol A; BPF, bisphenol F; BPS, bisphenol S; DEHP, di-2-ethylhexyl-phthalate metabolites; DNA, deoxyribonucleic acid; EDC, endocrine-disrupting chemical; E2, estradiol; T, testosterone; LH, luteinizing hormone; EP, ethyl paraben; E2, estradiol; MBP, mono-n-butyl phthalate; MBzP, monobenzyl phthalate; MCMHP, mono-[2-(carboxymethyl) hexyl] phthalate; MCPP, mono-3-carboxypropyl phthalate; MECPP, mono-2-ethyl-5-carboxypentyl phthalate; MEOHP, mono-2-ethyl-5-oxohexyl phthalate; MEHP, mono-2-ethylhexyl phthalate; MEHHP, mono-2-ethyl-5-hydroxyhexyl phthalate; MEP, monoethyl phthalate; MiNP, monoisononyl phthalate; MMP, monomethyl phthalate; MnBP, mono-n-butyl phthalate; MnOP, mono-n-octyl phthalate; MNP, monoisononyl phthalate; MiBP, monoisobutyl phthalate; MP, methyl paraben; PP, propyl paraben.