Environmental exposure to non-persistent endocrine disrupting chemicals and semen quality: An overview of the current epidemiological evidence.

Some of the recent publications have reported a decline in semen quality in the last few decades. This phenomenon is associated with environmental factors, particularly with exposure to endocrine disrupting chemicals (EDCs). The aim of this publication is to critically review the literature on exposure to the following 6 ubiquitous environmental non-persistent EDCs: bisphenol A, triclosan, parabens, synthetic pyrethroids, organophosphate pesticides and phthalates, and on their influence on semen quality measured as sperm concentration, sperm volume, total sperm count, motility, total motile count, morphology, sperm motion, sperm DNA damage (comet extent, tail length, tail distributed moment, percent of DNA located in the tail (tail%), DNA fragmentation index, high DNA stainability, X:Y ratio and aneuploidy. Several electronic databases were systematically searched until 31 August 2016. Studies were qualified for the review if they: linked environmental exposure to non-persistent EDCs to semen quality outcomes, were published in English after 2006 (and, in the case of phthalates, if they were published after 2009) and were conducted in the case of humans. Out of the 970 references, 45 articles were included in the review. This review adds to the body of evidence that exposure to non-persistent EDCs may affect semen quality parameters and decrease semen quality. Int J Occup Med Environ Health 2018;31(4):377–414

Zamkowska D ，Karwacka A ，Jurewicz J ，Radwan M ... -  《-》

Environmental and occupational pesticide exposure and human sperm parameters: A Navigation Guide review.

Global sperm counts have declined in recent decades, coinciding with the proliferation of endocrine-disrupting chemicals, of which pesticides are some of the most common. Previous systematic reviews of epidemiologic studies published between 1991 through 2013 have reported associations between environmental and occupational pesticide exposure and reduced sperm quality, particularly associations with reduced sperm concentration. This systematic review used the Navigation Guide to critically evaluate the current body of evidence examining sperm quality and pesticide exposure in epidemiological studies. PubMed, Scopus, and Web of Science databases were searched for all English-language articles published after September 2012 until August 2021. Original observational studies that assessed human sperm quality parameters, defined as concentration, motility, morphology, and DNA integrity, and individual-level pesticide exposure were included. The risk of bias for each included study and the strength of evidence were evaluated using the Navigation Guide protocol. Nineteen studies assessing environmental or occupational pesticide exposure and sperm parameters were included. Eighteen studies were cross-sectional studies and one prospective cohort; sample sizes ranged from 42 to 2122 men from 14 different countries. Fifteen (79 %) studies found at least one significant association between pesticide exposure and reduced sperm quality. The overall risk of bias across studies was classified as low to moderate. The quality of evidence was determined to be moderate based on systematic evaluation criteria. There were consistent adverse associations between pesticide exposure and sperm motility (63 % of studies) and DNA integrity (80 % of studies). For sperm concentration and morphology, 42 % and 36 % of studies found significant negative associations, respectively. The strength of the body of evidence overall was rated as having sufficient evidence of toxicity. Regarding specific sperm endpoints, there was sufficient evidence that pesticides are toxic for sperm motility and DNA integrity; limited evidence of toxicity for sperm concentration; and inadequate evidence of toxicity for sperm morphology. The studies reviewed here showed consistent associations between pesticide exposure and diminished sperm parameters, particularly sperm motility and sperm DNA integrity. These findings are largely consistent with results of previous reviews, which have found significant negative associations between pesticide exposure and sperm quality in 13 of 20 (65 %) studies published between 1991 and 2008, and in 14 of 17 (82 %) studies published between 2008 and 2012. After thirty years of mounting evidence, actions are needed to reduce pesticide risks to testicular function and male fertility.

Knapke ET ，Magalhaes DP ，Dalvie MA ，Mandrioli D ，Perry MJ ... -  《-》

Environmental non-persistent endocrine-disrupting chemicals exposure and reproductive hormones levels in adult men.

Non-persistent endocrine-disrupting chemicals (EDCs) are exogenous, man-made substances present in the environment that may interfere with the natural human hormones and may exert adverse consequences on human organism. Endocrinedisrupting chemicals have been suspected to be associated with altered reproductive function in the case of males and females. Environmental endocrine-disrupting non-persistent chemicals like parabens, phthalates, bisphenol A (BPA), synthetic pyrethroids and organophosphate pesticides are found in various products such as metal food cans, plastic bottles, detergents, personal care products or chemicals used for fighting against insects. The widespread distribution of these chemicals causes that humans are permanently exposed through multiple sources. The aim of this review is to summarize data linking non-persistent endocrine-disrupting chemicals exposure, and human, male reproductive hormones levels. The included studies were selected by searched PubMed, Web of Science and MEDLINE, original papers published from 2006 to 2016 and referring to human data were included to the review. The results of reviewed studies were not consistent, however, majority of the studies indicated that non-persistent EDCs may affect male reproductive hormones levels. Most findings suggest that exposure to environmental EDCs is negatively related to the level of testosterone (except for exposure to BPA which is positively associated). In most of the studies negative association was found between exposure to examined EDCs and free androgen index, too. Considering the suggested health effect of exposure to EDCs, more epidemiological data is needed. Int J Occup Med Environ Health 2018;31(5):551-573.

Dziewirska E ，Hanke W ，Jurewicz J 《-》

Preconception seminal plasma concentrations of endocrine disrupting chemicals in relation to semen quality parameters among male partners planning for pregnancy.

Some non-persistent endocrine disruptors (EDCs) are adversely associated with semen quality and few studies have measured those EDCs in seminal plasma. To find an association between EDCs in seminal plasma and semen quality parameters. Five chemical classes of non-persistent EDCs were quantified in seminal plasma from 339 male partners who participated in a prospective pregnancy study. Bisphenols, benzophenone UV-filters, antimicrobials and phthalate diesters and their monoester metabolites were measured using high performance liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry. Semen samples underwent next day analysis using a standardized protocol for the quantification of 35 endpoints. Linear mixed-effects models of EDCs that were log transformed and rescaled by their standard deviations or dichotomized at the 75th percentile for each exposure and outcomes with covariate adjustment were performed. EDCs in seminal plasma were also assessed relative to clinical reference values of semen quality endpoints using logistic regression or generalized estimating equations. The most consistent findings supporting adverse associations between seminal EDCs and semen quality were observed for some phthalate metabolites. For example, seminal plasma mono-ethyl, mono-n-butyl, mono-2-isobutyl and mono-benzyl phthalate concentrations were associated with decreased odds of having semen volume above clinical reference values (mEP: aOR=0.46; 95%CI= 0.32, 0.66; mBP: aOR=0.40; 95%CI= 0.28, 0.57; miBP: aOR=0.39; 95%CI= 0.27, 0.56), and mBzP: aOR= 0.34; 95%CI= 0.24, 0.49). Environmentally relevant concentrations of specific phthalates in seminal plasma were associated with diminished semen volume, sperm motility, viability, and morphological alterations in sperm heads such that semen volume and sperm viability fall below reference values.

Smarr MM ，Kannan K ，Sun L ，Honda M ，Wang W ，Karthikraj R ，Chen Z ，Weck J ，Buck Louis GM ... -  《-》

The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders: a systematic review and meta-analysis.

More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders. The aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commission's list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism. A systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data. The literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91-1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four compounds, p,p'-DDE, was related to an elevated risk: OR 1.35 (95% CI 1.04-1.74). The data did not indicate that this increased risk was driven by any specific disorder. The current epidemiological evidence is compatible with a small increased risk of male reproductive disorders following prenatal and postnatal exposure to some persistent environmental chemicals classified as endocrine disruptors but the evidence is limited. Future epidemiological studies may change the weight of the evidence in either direction. No evidence of distortion due to publication bias was found, but exposure-response relationships are not evident. There are insufficient data on rapidly metabolized endocrine disruptors and on specific exposure-outcome relations. A particular data gap is evident with respect to delayed effects on semen quality and testicular cancer. Although high quality epidemiological studies are still sparse, future systematic and transparent reviews may provide pieces of evidence contributing to the narrative and weight of the evidence assessments in the field.

Bonde JP ，Flachs EM ，Rimborg S ，Glazer CH ，Giwercman A ，Ramlau-Hansen CH ，Hougaard KS ，Høyer BB ，Hærvig KK ，Petersen SB ，Rylander L ，Specht IO ，Toft G ，Bräuner EV ... -  《-》