Journal of Environmental Treatment Techniques  
2020, Volume 8, Issue 1, Pages: 299-309  
J. Environ. Treat. Tech.  
ISSN: 2309-1185  
Journal web link: http://www.jett.dormaj.com  
Aspects of Environmental Pollutants on Male  
Fertility and Sperm Parameters  
Zohre Nateghian¹, Elham Aliabadi²  
1
PhD student of Anatomy, Department Anatomy, Shiraz University of Medical Sciences, Fars, Iran  
Associate Professor, Department Anatomy, Shiraz University of Medical Sciences, Fars, Iran  
2
Received: 13/09/2019  
Accepted: 22/11/2019  
Published: 20/12/2019  
Abstract  
Air pollution has considerable interest because it has multiple adverse effects on human health and the male reproductive  
system seems to be sensitive. For male fertility, environmental pollutants are vital owing to effects on semen quality. Male infertility  
is increasing in industrial countries with high air pollution. This review aims to investigate the effect of air pollution on fertility in  
humans based on available signs. Genetic and epigenetic alterations effect on the failure of male gamete. In this paper, we reviewed  
the major impacts of air pollutants on male infertility as well as the role of sperm DNA damage and epigenetic changes in male  
gamete. The DNA molecule and epigenetic changes, transmitted to future generations, can be altered and induced, respectively by  
some pollutants. A good knowledge on the effects of air contaminants on the molecular mechanisms leading to infertility is helpful  
for clinicians to identify the cause of infertility.  
Keywords: Environmental Pollutants, Male Fertility, Sperm Parameters  
1
Introduction  
In industrial countries, there has been an increase in  
infertility from 7% - 8% to 20% - 35% from 1960 by now,  
respectively (1). For the World Health Organization (WHO),  
the important priority is decreasing infertility rate (2). Based  
on some studies carried out, there has been a decrease in  
semen quality and sperm concentrations recently in most  
places in the world. In addition, there has been a noticeable  
decrease in human sperm concentrations from 113 to 61  
million/Ml (which shows 50% reduction) during the last50  
years (3). According to available evidence, fecundity and  
human semen quality have been decreasing during the last  
decades especially in Europe and the United States (2-4).  
Based on an estimate provided, there has been a decline by  
1
Corresponding author: Dr. Elham Aliabadi, Associate Professor, Department of Anatomy, Shiraz University of Medical  
Sciences, Fars, Iran. E-mail:aliabade@sums.ac.ir.  
299  
 
Journal of Environmental Treatment Techniques  
2020, Volume 8, Issue 1, Pages: 299-309  
1.5% each year in the sperm count in American males (5, 6).  
3
Mechanisms of action of air pollutants on  
However, there has been an increase in the infertility rate in  
Iran for the last 20 years. Studies show that in one-fourth  
Iranian couples are infertile; thus, by the end of their  
reproductive age three-fourth will be infertile. Furthermore,  
the infertility and the primary infertility rate have been  
increased by 20% and two-fold, respectively, for the last two  
decades (7). On the other hand, this idea that important  
factors might lead to decreasing semen in quality in some  
areas not all of them can be supported by geographical  
variations effects on semen quality (8, 9) as well as other  
changes which are in men reproductive functions(4,5).  
Lifestyle and environmental factors contribute toward these  
changes and constant exposure to environmental endocrine-  
disrupting chemicals has been provided (6). According to the  
reports, the malfunction of male reproductive system may be  
a well sensitive marker for environmental danger (4). Either  
gonadal endocrine disruption or direct damage to the  
spermatogenesis may cause the changes of male  
reproductive system (6). Investigating the unclear results  
obtained from the effect lead (Pb) and cadmium (Cd)  
elements on some variables, including male infertility,  
sperm parameters and hormone concentration has been  
carried out by epidemiological studies. (Give reference).  
Now, one of the most vital risk factors of metropolises is  
air pollution and it has an effect on all people, who live in  
urban areas. Owing to the importance of air pollution and  
effects, many studies have done to investigate adverse  
effects of it on the human health (10). Based on perinatal  
outcomes, there has been a correlation between air pollution  
and some adverse perinatal events, including reduced  
gestational period (11), preterm delivery (1214) and low  
birth weight (15). However, the effect of air pollution on the  
fertility has not been clear yet, it has been interested due to  
multiple adverse effects, which were reported on human  
health (1). The impacts of air pollution on some items,  
including in vitro fertilization (IVF) success rates (16),  
mammalian fertility and semen quality (1720) have been  
highlighted by some reports (21, 22). Clinical practice is  
tended to focus on the impacts of various air pollutants on  
fertility and knowing if subfertile populations are more  
sensitive toward these detrimental impacts. This review aims  
to investigate the effect of air pollution on fertility in humans  
based on available signs.  
fertility  
There have been 4 mechanisms for air pollutants effects  
on fertility, as follows: i) hormonal changes caused as a  
result of an endocrine disruptor action, ii) induction of  
oxidative stress, iii) cell DNA change and iv) epigenetic  
modifications. Air pollutants can play a key role as  
endocrine disruptors through activation of the aryl  
hydrocarbon receptor (AhR), estrogen or androgen receptors  
(
24). One of the common cellular mechanism caused air  
pollutants and used adverse effects is acting directly as pro-  
oxidants of lipids and proteins or as free radicals’ generators,  
developing the inflammatory responses induction and  
oxidative stress (25). The DNA molecule and epigenetic  
changes, including DNA methylation and histone  
modifications transmitted to future generations, can be  
altered and induced, respectively by some pollutants.  
3
.1 Action as endocrine disruptors  
All air pollutants especially the PAHs and heavy metals like  
Cu, Pb, Znin PM, notablyfrom diesel exhaust (26, 27), are  
discussed in the article as endocrine disruptors with either  
estrogenic, antiestrogenicor anti-androgenic activity (28–  
33).  
3
.2 Induction of reactive oxygen species (ROS)  
The most air pollutants like NO or O can generate ROS;  
2 3  
in addition, ROS is produced by particulate matters (PM)  
using the heavy metals and the PAHs. They are able to  
change by CYP450 dihydro-dehydrogenase producing  
quinone redox, catalyzing electron transfer reactions and  
hence stimulating ROS production (3437).  
3
.3 Cell DNA alteration  
Inducing alterations in the cell DNA is the third  
mechanism discussedin the paper in orderto explain the  
pathophysiologic mechanisms, which are in fertility  
alteration ledby air pollution. As discussed above, these  
DNA alterations could be relatedto oxidative stress, which is  
induced. Based on studies carried out on taxi drivers, DNA  
can be altered by the inflammation processes because of  
ROS (38). Besides, increasing annual some factors,  
x
including exposure to NO , inhalable particulate matter and  
fine particulate matter (PM-2·5) cause telomere length to  
increase (39). After forming of DNA adducts, they might  
occur. Since some of molecules can bind to a DNA base  
within covalent bonding, then change gene expression.  
Moreover, mutation incidence can lead to alternating the cell  
DNA and increasing apoptosis risk. Some of air pollutants  
are able to form DNA adducts in germ cells and the PAHs,  
which are in PM (40, 41, 42).  
2
Methods of Searching  
This study is a review investigating the effect of  
environmental air pollutants on reproductive health or  
fertility. The PubMed database is our source helping us to  
conduct the search in April 2019. In our study, there has been  
a combination of descriptors and terms correlated to air  
pollution and fertility so that every contaminant or substance  
such as gases, particulate matters, or volatile organic  
compounds in the air, which have an interference with  
human health or produce other harmful environmental  
effects, was considered as an air pollution (23). The entire  
search was conducted using the Advanced Search Builder  
and the keywords were found in ‘Title OR Abstract’.  
Wetried to filter the hits by selecting articles, which are  
written in English.  
4
Epigenetic modifications  
Epigenetic modifications, which are noticeable changes  
in DNA methylation, are able to cause abnormal gene  
expression. These abnormalities have roles in impact of air  
pollution upon respiratory failure (43, 44) and  
carcinogenesis (45). According to studies carried out by  
Ding et al, both hypomethylation and hypermethylation  
2
were shown in rats exposed to PM-10, PM-2.5and NO (46)  
and mitochondrial (mt) DNA canbe affected bythese  
300  
 
 
 
 
 
 
Journal of Environmental Treatment Techniques  
2020, Volume 8, Issue 1, Pages: 299-309  
changes (47). It was shown by Byun et al. blood mtDNA  
methylation, which is in the D-loop promoter, was  
accompanied with PM-2.5 levels (48).It was reported that  
epigenetic alterations are involved in the spermatogenesis  
failure (49). Based on findings of Stouder et al. (50),  
administration of alcohol in pregnant mice led to inducing  
hypomethylation of the H19 imprinted gene, in addition  
tothe decreased spermatogenesis. Furthermore, it is proven  
by Park et al., (51) that exposure to butylparaben (BP) for a  
long time can make DNA hypermethylation from the mitotic  
ina post-meiotic stage in tests for adult rats. Altering  
microRNA (miRNA) can occur by air pollutants. According  
to study done by Tsamou et al, the placental expression of  
miR-146a, miR-21 and miR-222, which are three miRNAs  
affected by air pollution exposure in leucocyte blood cells  
and also expressed in the placenta, was inversely  
accompanied with PM-2.5 exposure throughout the 2nd  
trimester of pregnancy (52). There are some details about  
environmental pollutants which are effective on male  
fertility as follows:  
morphology and sperm number and a male fertility  
impairment, epigenetic modification of sperm gene function  
can have an effect on the reproductive outcome. It is  
important to reprogram epigenome and-imprinted loci  
throughout gametogenes is and peri-implantation stagesin  
order to maintain a suitable inheritance pattern, especially at  
imprinted loci (61). Based on data obtained from literatures  
such as animal and human studies, there has been an  
increasing concern about risk of various diseases in the  
offspring made using assisted reproductive technologies (62;  
63). Most of abnormal conditions are correlated to  
epigenetic alterations, which lead into adversely affecting  
embryonic development and imprinting disorders, based on  
some strong evidence. To identify reasons of infertility and  
describe therapeutic and preventive protocols, clinicians  
need to have better information about air contaminants  
effects on the molecular mechanisms, which lead to male  
infertility (64).  
5.2 Environmental pollutants and changes in sperm  
parameters  
Air pollution as a common factor has an effect on  
reproductive functions in all countries for both men and  
women especially for sperm parameters in men. According  
the results obtained from meta-analysis that air pollution,  
however, decreases sperm motility, it does not affect the  
others parameters of spermogram. Some of stages in  
spermatogenesis and testicular size in mice were impaired  
and decreased, respectively, by post-natal and prenatal  
exposures to ambient air pollution (65). However, air  
pollution does not cause any changes in sperm counts in  
many studies; some abnormalities in DNA, sperm motility  
and morphology have been seen (66-69) and there is a  
negative correlation between air pollution and sperm counts  
specially in some population (70).  
A decrease in sperm counts can occur due to exposure to  
environmental pollution in the world (7177). In a reported  
done recently, it was shown that there is progressive  
decrease in sperm production throughout a period due to  
increasing air pollution in Greece (78). Although a  
relationship between either exposure to increasing air  
pollution or residence district and declined sperm  
production, including sperm per sample and concentration  
has not been found in the Czech Republic (66).  
However, there was poorer morphology (both years) and  
lower sperm motility from1994 samples for men sampled at  
the winter after increasing pollution in comparison with  
those of sampled after decreasing air pollution (Teplice in  
the fall and Prachatice the late winter or fall). Thus, based on  
the evidence, it is likely to have a relation between  
increasing air pollution and decreasing sperm quality. In  
addition, fertility data are not, however, available for this  
group of young men, there is a correlation between normal  
morphology and low values for sperm motility with  
infertility (7982). In study carried out by Selevan et al (66),  
it was found that there is highly noticeable relation between  
exposure to high (1993) air pollution, periods of medium  
5
Effects of environmental pollutants on male  
fertility  
5.1 Environmental pollutants and epigenetic changes in  
male germ cells  
Reliable evidence for damage to spermiogenes, which is  
caused by ambient air pollution exposure notable for  
genotoxic impacts and epigenetic alterations is provided by  
experimental and clinical studies. It is needed to have more  
investigations on the clinical relevance of air pollution-  
inducedi mpactsin male germ cells. Indeed, one of the  
clinical challenges has been the diagnosis of  
environmentally induced DNA damage or male infertility.  
The importance of the genotoxic impact on human  
spermatozoa is or both the offspring’s health and the  
reproductive performance of the men, who were exposed.  
There is a negative correlation between the semen quality  
and percentage of DNA-fragmented spermatozoa in an  
ejaculation (53; 54; 55). Although fragmented DNA with a  
spermatozoon is able to fertilize similarly an oocyte (56).  
Some studies have been carried out to show that the embryo  
and oocyte keep the ability to make a repair to DNA damage  
present in the paternal genome (57).Although there has been  
a question if all damage can be repaired. For example,  
double-stranded DNA breaks seem less repairable in  
comparison with single-stranded breaks and; therefore, they  
have a stronger effect on embryo development (58).  
Indeed, the oocyte is able to repair DNA, which has  
damage of sperm, for a certain level that damage caused in  
this level will lead to fragmenting low rate embryonic  
development and embryos. In addition, it was shown by  
Carrell et al, (59) that measurement of DNA fragmentation  
in men, with partners had pregnancy losses repeatedly, had  
higher levels. Therefore, some events, including impaired  
embryo morphology of blastocysts, fertilization failure,  
repeated spontaneous abortions or embryo implantation  
failure might happen.  
(
1994) and poor sperm morphology. Increasing air pollution  
According to evidence, epigenetic changes cause  
toxicity mediated from some environmental pollutants (60),  
thus, studies should be accurately carried out to investigate  
probable direct interactions between epigenetics alterations,  
air contaminants, and sperm abnormalities. By alterations in  
in winter 1993 was accompanied with increasing sperm  
percent and abnormal chromatin structure (COMPαt). In  
clinical studies, high COMPαt (> 30) has been accompanied  
with spontaneous abortion and infertility (83); however, this  
301  
 
 
 
Journal of Environmental Treatment Techniques  
2020, Volume 8, Issue 1, Pages: 299-309  
measure has been used recently for epidemiology studies. In  
another study, there was a relation between increasing  
COMPαt and exposure to cigarette smoke such as air  
pollution containing genotoxic PAHs and elevated COMPαt  
DNA fragmentation, which can be an important reason for  
undiagnosed/unexplained infertility, sperm DNA integrity  
has been considered as a better suggestion to predict male  
fertility better in comparison with common semen analysis.  
In a study carried out by Rubes et al. (94) in 2005, it was  
revealed that air pollution was correlated with increasing  
damage of DNA in human sperm without any other changes  
associated with semen quality such as motility and sperm  
concentration. These results proved preceding evidence of  
sperm morphological abnormalities (95, 66) in men, who  
live in the Teplice District in Northern Bohemia (Czech  
Republic) an place in which high-levelair pollution has been  
annually registered (96; 97). Radwan et al. (98) observed a  
statistically noticeable relation between exposure to all  
examined air pollutants and abnormalities in sperm  
morphology using analyzing infertile men based on normal  
semen concentrations. It is probable that sperm DNA  
fragmentation was the most common reason of paternal  
DNA noticeably transmission to progeny and found in a high  
percentage of spermatozoa from infertile men, subfertile and  
also from subjects, which were exposed to toxicants (99).  
In many studies, there has been a potential relation  
between fertility status and sperm DNA fragmentation (100-  
102). Rubes et al. (103,104) investigating seasonal  
differences in policemen worked in the center of Prague and  
exposed, which was verified by personal monitoring and  
ambient), revealed that there is notably higher DNA  
fragmentation in winter, that has high exposure compared to  
spring, that has low exposure for total non-smokers.  
Furthermore, it was seen a noticeable correlation between  
two standard indexes of DNA fragmentation, including Hdfi  
and detDFI with% of sperm with only high DNA damage  
and detectable DNA fragmentation Index, respectively, and  
specific genetic modification on DNA repair genes. A  
correlation was between immature sperm and  
polymorphisms in GSTM1 gene codifying for one of the  
enzymes, which generally defend from many toxicants, and  
supported the genetic polymorphisms role as potential  
modifiers of associations between modifications in sperm  
quality and air pollution exposure (103,104). On the other  
hand, the idea for special factors, which present in some  
areas not all of them, might be in charge of declining semen  
quality, is maintained by the impact of geographical  
variables in the quality of semen and other alterations in men  
reproductive function (105-107).  
(
84). Thus, it can be deducted that smoking was kept in the  
COMPαt model. Regarding this, other measurement of  
genetic integrity called sperm aneuploidy noticeably  
increased in a subset of the same men exposed to high air  
pollution, including nonsmokers from the Teplice winter  
1993 group in comparison with those exposed to low air  
pollution, including nonsmokers from the Teplice summer  
1993 group, who were from Czech (84).  
5.3 Environmental pollutants and changes in sperm DNA  
integrity and telomeres  
Nowadays, it is believed, based on the available  
evidence, that sperm DNA integrity maybe a better factor to  
predict male fertility potentiality in comparison with  
common semen parameters (85). However, the most routine  
method used in a clinical setting called DNA fragmentation  
might not to be able to give complete information about  
DNA damages everityand the molecular mechanisms (85).  
Thus, it is needed urgently for male germ line cells to have  
more sensitive biomarkers of DNA integrity. Recently, there  
have been many studies about the effect of sperm telomeres  
in male infertility and reproduction (86). According to  
results obtained from studies, sperm telomere length could  
be as an extra sperm quality parameter which might add  
information regarding DNA damage and make a new way in  
evaluating infertile males (87, 88).It was shown, by a study  
conducted recently, that a probable relation has been  
between sperm telomere length and high environmental  
pressure, in which polluted areas (89).  
Based on a study carried out recently, environmental  
exposure with high level might lead to increasing semen  
telomere length (TL) in young normospermic men, who  
have important effects and roles on sperm as a sensitive  
sentinel biomarker of environmental impactsthat was  
obtained for the first time (90). In addition, it has been shown  
tha tembryo quality development sperm and sperm telomere  
length (STL) have been correlated and TL is higher in  
normozoospermic than oligozoospermic men (91). The  
pollutants effect on semen telomere length has been  
evaluated in a just one study owing to a few types of PAHs;  
there was a shortening in semen TL ledby an impairment in  
telomerase (89) and it is shown that there has been a  
noticeable increase in telomere length in sperm for young  
men who live in places with high environmental pollutants  
exposure than others. These results reveal that one of the  
sensitive sentinel biomarkers of environmental exposure is  
semen. To do morestudies in majorpopulations, it is  
necessary to know the importance of telomere lengthening  
in places with high environmental situations.  
5.5 Environmental pollutants and Epigenetic changes and  
male infertility  
Heritable alterations in gene expression and in  
phenotype without changes in the DNA sequence are defined  
based on Epigenetics containing chemical changes to histone  
proteins related to DNA (histone modifications), the  
cytosine residues of DNA (DNA methylation) in addition to  
posttranscriptional regulation by noncoding microRNAs.  
Despite of the similarity of DNA sequence between humans,  
there has been a large epigenetic difference (108). Some  
diseases might be caused bychanges of epigenetic profile  
responding to environmental stimuli, and epigenetic  
modifications triggered by environmental exposure (109-  
111). There has not carried out any studies yet to investigate  
the direct impact of environmental toxicant exposure on  
male fertility abnormality and epigenetic stat; however, there  
5
.4 Environmental pollutants and sperm DNA damage  
Fertility can be affected by chromosomal aberrations,  
either structural or numerical. The chromosomal aberration  
sfrequency is approximately 0.6 %in the total population  
(
92), while increaseup2%14% in infertile males (93).There  
has been an increase in chromosomal aberrations due to  
increasing severity of infertility. In conclusion, as men, who  
have normal semen parameters, might have high-degree  
302  
 
 
 
Journal of Environmental Treatment Techniques  
2020, Volume 8, Issue 1, Pages: 299-309  
issome animal evidence making a suggestion that epigenome  
is altered by environment-induced abnormality in sperm  
parameters (112,113). Epigenetics mechanisms ultimately  
regulating the activity of gene and expression throughout  
differentiation and development are basic mechanisms for  
normal spermatogenesis and gonadal development (114-  
in Leydig cells on the testicular level, (126); Watanabehas  
reported a Sertoli cells reduction in rats, which were exposed  
todiesel exhaust (127). It was shown by Jeng and Yuhaveon  
the hormonal level that prolonged exposure to PAHs leads  
to decreasing and increasing in blood testosterone levels and  
LH levels, respectively, at the end of the exposure time (46).  
It was found byInyang et al. that there is a statistically  
noticeable decrease and increase in levels of blood  
testosterone and LH levels, respectively, in rats, which were  
exposed toa type of PAH: benzo (a) pyrene (134). According  
to study carried out on rates by Tsukue et al., hormonal  
alterationsin the group, which were exposed to diesel  
exhaust with a statistically noticeable increase in levels of  
blood testosterone and LH, were correlated with  
modifications in the weight of the accessory sex glands such  
as seminal vesicles and prostate (135). It was reported by  
Watanabe and Oonuki that there was a statistically  
noticeable increase in testosterone and estrogens levels and  
a noticeable decrease in the levels of FSH and LH in a group  
of rats, which were exposed to diesel exhaust. Moreover, an  
increase in degenerative cells was observed between  
spermatid and the spermatocytestages (130).  
116). It has been clear that special errors, which are in the  
procedure of epigenetic control, mightoccur throughout  
every stage of spermatogenesis, negatively, having an effect  
on embryonic development and male fertility and (117).  
Inrecent meta-analysis, alterations in miRNA profile  
caused sensitive indicators made from impacts of chronic  
and acute environmental exposure (118). There has not been  
published any special studies yet; however, the available  
data strongly makes a suggestion that air pollutants could  
have an impact on the miRNA signature, which are needed  
for normal spermatogenesis. miRNAs have an important  
role in meiosis, mitosis and spermatogenesis (119-121). In  
order to participate in every step control of male germ cell  
differentiation, throughout spermatogenesis, the miRNAs  
are stated in a cell-specific manner. The significance of  
miRNA paths for normal spermatogenesis has been revealed  
bymodels of genetically modified mouse, and functional  
studies have been conducted in order to dissect the specific  
miRNAs roles in different cell type (122). Based on clinical  
studies, spermatozoa from patients with seminal changes  
shows a differential miRNA profile (123,124). Therefore, on  
the one hand, there is a hard evidence of miRNA important  
role in spermatogenesis contributing to the mechanisms,  
which are involved in human fertility; on the other hand, the  
profile of miRNA expression has been offered as a new non-  
invasive, diagnostic biomarker of male fertility. Study  
conducted by Wang et al. (125), investigated samples of  
pooled semen acquired from infertile men and the results in  
comparison with normal fertile individuals as control  
groups. It was revealed that changes in miRNA profiles in  
both asthenozoospermia and azoospermia. The seven  
miRNAs level was noticeably lower and higher in  
azoospermia and asthenozoospermia, respectively, in  
comparison with control. Therefore, it was proposed by the  
authors that seven miRNAs may confirm molecular  
diagnostic value for infertility in males.  
5.7 Impact of Environmental pollutants on the male  
gamete in humans  
In the past few decades, there was a decrease in the  
sperm quality in industrialized countries (136, 137). The  
exposure to toxic materials in ambient and the environment  
air pollution can be a probable cause for these changes (138–  
140). Indeed, it has been revealed that professions, which  
were exposed to exhaust like toll collectors and worked on  
expressways, more regularly generate sperm abnormalities  
(141, 142).However, this paper is rich in this subject, there  
have not been enough studies on it since they do not  
investigate the same pollutants and their methods are  
different based on populations studied during exposure time.  
Besides, results obtained are not sometimes in agreement.  
Although many studies reveal modifications, after  
exposure to air pollution, in parameters of sperm, giving  
evidence for decreasing the quality of sperm. These changes  
have a decrease in either sperm mobility (138, 140146), or  
in the movement quality (138, 140). In addition, a decrease  
in the percentage of normal shapes, especially head  
morphology, along with changed sperm morphology is  
regularly mentioned (66, 140, 142,144150, 151). Results  
obtained for sperm counts are not in agreement with a few  
studies reporting a noticeable decline in the concentration of  
sperm in semen after exposure to specific forms of air  
pollution (140, 142, 144, 149, and 152); however, others do  
not report noticeable impacts (66, 148, and 153). The results  
can be true for the proportion of alive spermatozoa such as  
sperm vitality, with a few studies investigating a noticeably  
negative impact of air pollution on these parameters (138,  
146).  
5.6 Impact of Environmental pollutants on the male  
gamete in animals  
Studies conductedout on animals have revealed that  
different forms of air pollution have detrimental impactson  
the quality of sperm. A statistically noticeable decline in  
spermatozoa production has been expressedwhich is along  
with increasing abnormal sperm shapes in rats and  
miceexposed to car exhaust, remarkably from diesel vehicles  
(
126130). It has been reported that there is an impact on the  
nuclear quality of spermatozoa (131). It was observed by  
Yauk et al. that there was a statistically noticeable increase  
in sperm DNA breakage and hypermethylation in mice  
which were exposed to air pollutedin a Canadian city (132).  
There was a noticeable increase in the mutations rate, which  
wasfound in sperm DNA, particularly on the loci of DNA  
sequence repeats. The probability of genetic mutations in  
germ line cell’s DNA increased by this last phenomenon  
such as spermatozoa, which are transmitted to descendants  
Guven et al. carried out a study on comparison sperm  
parameters at males, who were exposed to exhaust from  
diesel vehicles during work at toll plazas on pathways with  
unexposed males, who worked as official personnel in the  
exact company. The exposed group had a statistically  
noticeable decline in sperm mobility, sperm counts as well  
as sperm morphology especially cephalic faults (142).  
Selevan et al, conducted a study on parameters of sperm in  
(
133). However, Yoshida et al. reported structural alterations  
303  
 
 
Journal of Environmental Treatment Techniques  
2020, Volume 8, Issue 1, Pages: 299-309  
healthy young males from two areas of the CzechRepublic,  
a coal-producing region with high levels of air pollution  
parameters of sperm for the 4 air pollutants calculated at  
region, including PM-10,CO, NO andO ) after alteration for  
2 3  
(
Teplice) and a less-polluted region (Prachatice).  
many factors such as abstinence period and the other air  
pollutants. There was a 4.22% decline in concentration of  
In comparison with the low level of exposure, it was  
found that there a statistically noticeable negative effect of  
exposure to high and medium air pollution levels on the  
proportion of motile sperm that they are respectively for low,  
medium and high exposure are as follows: 36.2% ± 17;  
3
sperm per inter quartile range (IQR) of increase in O (p =  
0.01)for every exposure until before semen collection 9  
days. Moreover, there was 2.92% and 3.90% declines in  
3
concentration of sperm per IQR for an increase in O ,  
27.9% ± 18.1and 32.5% ± 13.2. Those was also true for  
respectively (p = 0.05 in both cases) (156) for the exposure  
sperm morphology, noticeably sperm heads. On the other  
hand, In comparison with the low level of exposure, they did  
not have an impact of high or medium exposure to air  
pollution on all sperm count which are respectively for low,  
medium and high exposure as follows: 113.5 ± 130.7  
million/ejaculate; 100.9 ± 97.6 and 129.1 ± 103.1 (66). The  
same team revealed that therea statistically noticeable  
increase in the percentage of spermatozoa along with  
abnormal chromatin such as abnormalities in DNA  
compaction and fragmentation in males, who were exposed  
to air pollution with high levels in the Teplice are of Czech  
Republic (153). Thus, these studies offer that air pollution  
might change sperm DNA (131, 154). Based on these  
observations, it was expressed by other authors that there is  
a probable impactof air pollution upon the sperm genome at  
the chromosomal level (144, 155). Therefore, the rate of  
aneuploidy in the sperm of Polish men associated with  
normal sperm concentrations (> or = 15 million/ml), which  
consult for infertility was measured by Jurewiczet al. (155).  
It was observed that there a noticeable relation between the  
rate of aneuploidy as well as exposure to sure air pollutants,  
significantly Y-chromosome disomy and disomy21 and PM-  
1014 days and 7090 days before ejaculation.  
6
Conclusion  
Clinical and experimental studies provide important  
evidence for damage to male gamete caused by air pollution  
for its genotoxic effects and epigenetic alterations.  
Diagnosis of environmentally induced male infertility by  
clinicians is likely to remain a challenge. An accurate  
knowledge of genotoxic effect on spermatogenesis is  
important not only for the fertility of the men exposed, but  
also for the offsprings health. Indeed, the percentage of  
DNA-fragmented spermatozoa in an ejaculate negatively  
correlates with semen quality on the other hand it is now  
clear that also a spermatozoon with fragmented DNA can  
fertilize an oocyte and cause to abnormal offspring. Indeed,  
the effect of epigenetic modification of sperm gene function  
can affect the reproductive outcome.  
A large amount of literature data, including human and  
animal studies strongly suggest that the majority of risk of  
different diseases in the offspring are related to epigenetic  
alterations leading to imprinting disorders and adversely  
affecting embryonic development. A good knowledge about  
the effects of air contaminants on the molecular mechanisms  
cause to male infertility could help the clinicians to identify  
the cause of infertility and to define preventive and  
therapeutic protocol.  
10 (β = 0.58 (95% CI: 0.46–0.72)), PM-2.5 (β = 0.68 (95%  
CI: 0.550.85)) and PM-2.5 (β = 0.78 (95% CI: 0.62–0.97)),  
after alteration for 12 confusing factors, including smoking,  
age ,season, alcohol consumption, , abstinence interval, past  
diseases, distance from the monitoring station,.  
Recently, it was reported by some authors that there is  
an alteration in the circulating levels of hormones in the  
gonadal axis, which follows exposure to air pollution.  
According to study carried out by De Rosa et al., there is a  
comparison between a group of exposed men, who work at  
a toll plaza on an pathway and an unexposed group, who  
work as drivers, clerks, doctors and students or live in the  
same geographical region. According to altering sperm  
parameters, a noticeably higher level of FSH was observed  
in the group that were exposed (mean ± SE: 4.1 ± 0.3 UI/l vs  
References  
1
. Thompson ST. Preventable causes of male infertility. World  
journal of urology. 1993 May 1;11(2):111-9.  
2. Sharma R, Biedenharn KR, Fedor JM, Agarwal A. Lifestyle  
factors and reproductive health: taking control of your fertility.  
Reproductive Biology and Endocrinology. 2013 Dec;11(1):66.  
3
. Joffe M. Infertility and environmental pollutants. British medical  
bulletin. 2003 Dec 1;68(1):47-70.  
4
. Hauser R, Sokol R. Science linking environmental contaminant  
exposures with fertility and reproductive health impacts in the  
adult male. Fertility and sterility. 2008 Feb 1;89(2):e59-65.  
. Akre O, Cnattingius S, Bergström R, Kvist U, Trichopoulos D,  
Ekbom A. Human fertility does not decline: evidence from  
Sweden. Fertility and sterility. 1999 Jun 1;71(6):1066-9.  
3.2 ± 0.2; p < 0.05); however, it was kept within range of  
5
normal value (138). It was also found by Radwan et al. (150)  
that there is a negative correlation between exposure to  
specific air pollutants testosterone levels (PM-10, PM-2.5,  
6. Hammoud A, Carrell DT, Gibson M, Sanderson M, Parker-Jones  
K, Peterson CM. Decreased sperm motility is associated with  
air pollution in Salt Lake City. Fertility and sterility. 2010 Apr  
CO and NO  
x
).  
Therefore, there is  
a
strong evidence regarding  
1
;93(6):1875-9.  
detrimental impacts of air pollution on male reproductive  
parameters; in addition, a decreased in male fertility can be  
in interest. Although, the many studies of human are  
retrospective. It was found just one study on a 2-year period  
in the youth, who were nonsmoker with healthy sperm  
donors from Los Angeles, California (152). The sample was  
completely small (n = 48) and only motility and sperm  
concentration were investigated. Although, every sperm  
donor gave sample at least 10 times at the duration studied  
7
. Safarinejad MR. Infertility among couples in a populationbased  
study in Iran: prevalence and associated risk factors.  
International journal of andrology. 2008 Jun;31(3):303-14.  
8. Auger J, Kunstmann JM, Czyglik F, Jouannet P. Decline in semen  
quality among fertile men in Paris during the past 20 years. New  
England Journal of Medicine. 1995 Feb 2;332(5):281-5.  
9
. Mendiola J, Jørgensen N, Andersson AM, Stahlhut RW, Liu F,  
Swan SH. Reproductive parameters in young men living in  
Rochester, New York. Fertility and sterility. 2014 Apr  
1
;101(4):1064-71  
3
period. Only O exposure revealed a noticeable effect on  
304  
 
 
Journal of Environmental Treatment Techniques  
2020, Volume 8, Issue 1, Pages: 299-309  
.
10. Brunekreef B, Holgate ST. Air pollution and health. The lancet.  
Environmental sciences: an international journal of  
environmental physiology and toxicology. 2004;11(1):33-45.  
27. Wang J, Xie P, Kettrup A, Schramm KW. Inhibition of  
progesterone receptor activity in recombinant yeast by soot  
from fossil fuel combustion emissions and air particulate  
materials. Science of the total environment. 2005 Oct 15;349(1-  
3):120-8.  
2
002 Oct 19;360(9341):1233-42.  
1
1. Candela S, Ranzi A, Bonvicini L, Baldacchini F, Marzaroli P,  
Evangelista A, Luberto F, Carretta E, Angelini P, Sterrantino  
AF, Broccoli S. Air pollution from incinerators and  
reproductive outcomes: a multisite study. Epidemiology. 2013  
Nov 1:863-70.  
2
8. Okamura K, Kizu R, Toriba A, Murahashi T, Mizokami A,  
Burnstein KL, Klinge CM, Hayakawa K. Antiandrogenic  
activity of extracts of diesel exhaust particles emitted from  
diesel-engine truck under different engine loads and speeds.  
Toxicology. 2004 Feb 15;195(2-3):243-54.  
1
1
2. Dadvand P, Parker J, Bell ML, Bonzini M, Brauer M, Darrow  
LA, Gehring U, Glinianaia SV, Gouveia N, Ha EH, Leem JH.  
Maternal exposure to particulate air pollution and term birth  
weight: a multi-country evaluation of effect and heterogeneity.  
Environmental health perspectives. 2013 Feb 6;121(3):267-  
29. Han Y, Xia Y, Zhu P, Qiao S, Zhao R, Jin N, Wang S, Song L,  
Fu G, Wang X. Reproductive hormones in relation to polycyclic  
aromatic hydrocarbon (PAH) metabolites among non-  
occupational exposure of males. Science of the total  
environment. 2010 Jan 15;408(4):768-73.  
30. Taneda S, Hayashi H, Sakata M, YOSHINO S, SUZUKI A,  
SAGAI M, MORI Y. Anti-estrogenic activity of diesel exhaust  
particles. Biological and Pharmaceutical Bulletin. 2000 Dec  
1;23(12):1477-80.  
31. Oh SM, Ryu BT, Chung KH. Identification of estrogenic and  
antiestrogenic activities of respirable diesel exhaust particles by  
bioassay-directed fractionation. Archives of pharmacal  
research. 2008 Jan 1;31(1):75-82.  
32. Noguchi K, Toriba A, Chung SW, Kizu R, Hayakawa K.  
Identification of estrogenic/antiestrogenic compounds in diesel  
exhaust particulate extract. Biomedical Chromatography. 2007  
Nov;21(11):1135-42.  
3
73.  
3. Pedersen M, Giorgis-Allemand L, Bernard C, Aguilera I,  
Andersen AM, Ballester F, Beelen RM, Chatzi L, Cirach M,  
Danileviciute A, Dedele A. Ambient air pollution and low  
birthweight: a European cohort study (ESCAPE). The lancet  
Respiratory medicine. 2013 Nov 1;1(9):695-704.  
4. Laurent O, Wu J, Li L, Chung J, Bartell S. Investigating the  
association between birth weight and complementary air  
pollution metrics: a cohort study. Environmental Health. 2013  
Dec;12(1):18.  
5. Estarlich M, Ballester F, Aguilera I, Fernández-Somoano A,  
Lertxundi A, Llop S, Freire C, Tardón A, Basterrechea M,  
Sunyer J, Iñiguez C. Residential exposure to outdoor air  
pollution during pregnancy and anthropometric measures at  
birth in a multicenter cohort in Spain. Environmental health  
perspectives. 2011 Mar 23;119(9):1333-8.  
1
1
1
1
1
1
6. Frutos V, González-Comadrán M, Sola I, Jacquemin B, Carreras  
R, Checa Vizcaino MA. Impact of air pollution on fertility: a  
systematic review. Gynecological Endocrinology. 2015 Jan  
33. Yoshida S, Hirano S, Shikagawa K, Hirata S, Rokuta S, Takano  
H, Ichinose T, Takeda K. Diesel exhaust particles suppress  
expression of sex steroid hormone receptors in TM3 mouse  
Leydig cells. Environmental toxicology and pharmacology.  
2007 Nov 1;24(3):292-6.  
34. Agarwal A, Allamaneni SS. Free radicals and male  
reproduction. Journal of the Indian medical association. 2011  
Mar;109(3):184-7.  
2
;31(1):7-13.  
7. Guven A, Kayikci A, Cam K, Arbak P, Balbay O, Cam M.  
Alterations in semen parameters of toll collectors working at  
motorways: does diesel exposure induce detrimental effects on  
semen?. Andrologia. 2008 Dec;40(6):346-51.  
8. Hammoud A, Carrell DT, Gibson M, Sanderson M, Parker-Jones  
K, Peterson CM. Decreased sperm motility is associated with  
air pollution in Salt Lake City. Fertility and sterility. 2010 Apr  
35. Arbak P, Yavuz O, Bukan N, Balbay O, Ulger F, Annakkaya  
AN. Serum oxidant and antioxidant levels in diesel exposed toll  
collectors. Journal of occupational health. 2004;46(4):281-8.  
36. Cho AK, Sioutas C, Miguel AH, Kumagai Y, Schmitz DA,  
Singh M, Eiguren-Fernandez A, Froines JR. Redox activity of  
airborne particulate matter at different sites in the Los Angeles  
Basin. Environmental research. 2005 Sep 1;99(1):40-7.  
37. Sklorz M, Briedé JJ, Schnelle-Kreis J, Liu Y, Cyrys J, de Kok  
TM, Zimmermann R. Concentration of oxygenated polycyclic  
aromatic hydrocarbons and oxygen free radical formation from  
urban particulate matter. Journal of Toxicology and  
Environmental Health, Part A. 2007 Sep 28;70(21):1866-9.  
38. Barth A, Brucker N, Moro AM, Nascimento S, Goethel G, Souto  
C, Fracasso R, Sauer E, Altknecht L, Da Costa B, Duarte M.  
Association between inflammation processes, DNA damage,  
and exposure to environmental pollutants. Environmental  
Science and Pollution Research. 2017 Jan 1;24(1):353-62.  
39. Walton RT, Mudway IS, Dundas I, Marlin N, Koh LC, Aitlhadj  
L, Vulliamy T, Jamaludin JB, Wood HE, Barratt BM, Beevers  
S. Air pollution, ethnicity and telomere length in east London  
schoolchildren: an observational study. Environment  
international. 2016 Nov 1;96:41-7.  
40. Gaspari L, Chang SS, Santella RM, Garte S, Pedotti P, Taioli E.  
Polycyclic aromatic hydrocarbon-DNA adducts in human  
sperm as a marker of DNA damage and infertility. Mutation  
Research/Genetic Toxicology and Environmental Mutagenesis.  
2003 Mar 3;535(2):155-60.  
41. Jeng HA, Yu L. Alteration of sperm quality and hormone levels  
by polycyclic aromatic hydrocarbons on airborne particulate  
particles. Journal of Environmental Science and Health, Part A.  
2008 Apr 29;43(7):675-81.  
1
;93(6):1875-9.  
9. Rubes J, Selevan SG, Evenson DP, Zudova D, Vozdova M,  
Zudova Z, Robbins WA, Perreault SD. Episodic air pollution is  
associated with increased DNA fragmentation in human sperm  
without other changes in semen quality. Human Reproduction.  
2
005 Jun 24;20(10):2776-83.  
2
0. Rubes J, Selevan SG, Sram RJ, Evenson DP, Perreault SD.  
GSTM1 genotype influences the susceptibility of men to sperm  
DNA damage associated with exposure to air pollution.  
Mutation research/fundamental and molecular mechanisms of  
mutagenesis. 2007 Dec 1;625(1-2):20-8.  
1. Januário DA, Perin PM, Maluf M, Lichtenfels AJ, Nascimento  
Saldiva PH. Biological effects and dose-response assessment of  
diesel exhaust particles on in vitro early embryo development  
in mice. Toxicological Sciences. 2010 Jun 4;117(1):200-8.  
2. Mohallem SV, de Araujo Lobo DJ, Pesquero CR, Assuncao JV,  
de Andre PA, Saldiva PH, Dolhnikoff M. Decreased fertility in  
mice exposed to environmental air pollution in the city of Sao  
Paulo. Environmental research. 2005 Jun 1;98(2):196-202.  
3. Vizcaíno MA, Gonzalez-Comadran M, Jacquemin B. Outdoor  
air pollution and human infertility: a systematic review.  
Fertility and Sterility. 2016 Sep 15;106(4):897-904.  
2
2
2
2
4. De Coster S, Van Larebeke N. Endocrine-disrupting chemicals:  
associated disorders and mechanisms of action. Journal of  
environmental and public health. 2012;2012.  
5. Kampa M, Castanas E. Human health effects of air pollution.  
Environmental pollution. 2008 Jan 1;151(2):362-7.  
2
2
6. Takeda K, Tsukue N, Yoshida S. Endocrine-disrupting activity  
of chemicals in diesel exhaust and diesel exhaust particles.  
42. Rubes J, Selevan SG, Evenson DP, Zudova D, Vozdova M,  
Zudova Z, Robbins WA, Perreault SD. Episodic air pollution is  
305  
Journal of Environmental Treatment Techniques  
2020, Volume 8, Issue 1, Pages: 299-309  
associated with increased DNA fragmentation in human sperm  
without other changes in semen quality. Human Reproduction.  
60. Baccarelli A, Bollati V. Epigenetics and environmental  
chemicals. Current opinion in pediatrics. 2009 Apr;21(2):243.  
61. Barakat TS, Jonkers I, Monkhorst K, Gribnau J. X-changing  
information on X inactivation. Experimental cell research. 2010  
Mar 10;316(5):679-87.  
62. Pinborg A, Henningsen AK, Malchau SS, Loft A. Congenital  
anomalies after assisted reproductive technology. Fertility and  
sterility. 2013 Feb 1;99(2):327-32.  
63. Shufaro Y, Laufer N. Epigenetic concerns in assisted  
reproduction: update and critical review of the current  
literature. Fertility and sterility. 2013 Mar 1;99(3):605-6.  
64. Vecoli C, Montano L, Andreassi MG. Environmental pollutants:  
genetic damage and epigenetic changes in male germ cells.  
Environmental Science and Pollution Research. 2016 Dec  
1;23(23):23339-48.  
65. Pires A, de Melo EN, Mauad T, Nascimento Saldiva PH, de  
Siqueira Bueno HM. Pre-and postnatal exposure to ambient  
levels of urban particulate matter (PM2. 5) affects mice  
spermatogenesis. Inhalation toxicology. 2011 Mar 1;23(4):237-  
45.  
2
005 Jun 24;20(10):2776-83.  
4
3. Lepeule J, Bind MA, Baccarelli AA, Koutrakis P, Tarantini L,  
Litonjua A, Sparrow D, Vokonas P, Schwartz JD. Epigenetic  
influences on associations between air pollutants and lung  
function in elderly men: the normative aging study.  
Environmental health perspectives. 2014 Mar 6;122(6):566-72.  
4. Holloway JW, Savarimuthu Francis S, Fong KM, Yang IA.  
Genomics and the respiratory effects of air pollution exposure.  
Respirology. 2012 May;17(4):590-600.  
5. Cao Y. Environmental pollution and DNA methylation:  
carcinogenesis, clinical significance, and practical applications.  
Frontiers of medicine. 2015 Sep 1;9(3):261-74.  
6. Ding R, Jin Y, Liu X, Zhu Z, Zhang Y, Wang T, Xu Y.  
Characteristics of DNA methylation changes induced by traffic-  
related air pollution. Mutation Research/Genetic Toxicology  
and Environmental Mutagenesis. 2016 Jan 15;796:46-53.  
7. Byun HM, Barrow TM. Analysis of pollutant-induced changes  
in mitochondrial DNA methylation. InMitochondrial Medicine  
4
4
4
4
4
2
015 (pp. 271-283). Humana Press, New York, NY.  
66. Selevan SG, Borkovec L, Slott VL, Zudová Z, Rubes J, Evenson  
DP, Perreault SD. Semen quality and reproductive health of  
young Czech men exposed to seasonal air pollution.  
Environmental Health Perspectives. 2000 Sep;108(9):887-94.  
67. Rubes J, Selevan SG, Evenson DP, Zudova D, Vozdova M,  
Zudova Z, Robbins WA, Perreault SD. Episodic air pollution is  
associated with increased DNA fragmentation in human sperm  
without other changes in semen quality. Human Reproduction.  
2005 Jun 24;20(10):2776-83.  
68. Hammoud A, Carrell DT, Gibson M, Sanderson M, Parker-Jones  
K, Peterson CM. Decreased sperm motility is associated with  
air pollution in Salt Lake City. Fertility and sterility. 2010 Apr  
1;93(6):1875-9.  
8. Byun HM, Colicino E, Trevisi L, Fan T, Christiani DC,  
Baccarelli AA. Effects of air pollution and blood mitochondrial  
DNA methylation on markers of heart rate variability. Journal  
of the American Heart Association. 2016 Apr 22;5(4):e003218.  
9. Vecoli C, Montano L, Andreassi MG. Environmental pollutants:  
genetic damage and epigenetic changes in male germ cells.  
Environmental Science and Pollution Research. 2016 Dec  
4
1
;23(23):23339-48.  
0. Stouder C, Somm E, Paoloni-Giacobino A. Prenatal exposure to  
ethanol: specific effect on the H19 gene in sperm.  
5
5
5
a
Reproductive Toxicology. 2011 May 1;31(4):507-12.  
1. Park CJ, Nah WH, Lee JE, Oh YS, Gye MC. Butyl paraben‐  
induced changes in DNA methylation in rat epididymal  
spermatozoa. Andrologia. 2012 May;44:187-93.  
2. Tsamou M, Vrijens K, Madhloum N, Lefebvre W, Vanpoucke  
C, Nawrot TS. Air pollution-induced placental epigenetic  
69. Hansen C, Luben TJ, Sacks JD, Olshan A, Jeffay S, Strader L,  
Perreault SD. The effect of ambient air pollution on sperm  
quality. Environmental health perspectives. 2009 Sep  
18;118(2):203-9.  
alterations in early life:  
Epigenetics. 2018 Feb 1;13(2):135-46.  
a
candidate miRNA approach.  
70. Guven A, Kayikci A, Cam K, Arbak P, Balbay O, Cam M.  
Alterations in semen parameters of toll collectors working at  
motorways: does diesel exposure induce detrimental effects on  
semen?. Andrologia. 2008 Dec;40(6):346-51.  
71. Toppari J, Larsen JC, Christiansen P, Giwercman A, Grandjean  
P, Guillette Jr LJ, Jégou B, Jensen TK, Jouannet P, Keiding N,  
Leffers H. Male reproductive health and environmental  
xenoestrogens. Environmental health perspectives. 1996  
Aug;104(suppl 4):741-803.  
5
3. Lopes S, Sun JG, Jurisicova A, Meriano J, Casper RF. Sperm  
deoxyribonucleic acid fragmentation is increased in poor-  
quality semen samples and correlates with failed fertilization in  
intracytoplasmic sperm injection. Fertility and sterility. 1998  
Mar 1;69(3):528-32.  
4. IRVINE DS, TWIGG JP, GORDON EL, FULTON N, MILNE  
PA, AITKEN RJ. DNA integrity in human spermatozoa:  
relationships with semen quality. Journal of andrology. 2000  
Jan 2;21(1):33-44.  
5. MURATORI M, PIOMBONI P, BALDI E, FILIMBERTI E,  
PECCHIOLI P, MORETTI E, GAMBERA L, BACCETTI B,  
BIAGIOTTI R, FORTI G, Maggi M. Functional and  
ultrastructural features of DNAfragmented human sperm.  
Journal of andrology. 2000 Nov 12;21(6):903-12.  
6. Yamauchi Y, Riel JM, Ward MA. Paternal DNA damage  
resulting from various sperm treatments persists after  
fertilization and is similar before and after DNA replication.  
Journal of andrology. 2012 Mar 4;33(2):229-38.  
5
5
72. Acacio BD, Gottfried T, Israel R, Sokol RZ. Evaluation of a  
large cohort of men presenting for a screening semen analysis.  
Fertility and sterility. 2000 Mar 1;73(3):595-7.  
73. Andersen AG, Jensen TK, Carlsen E, Jørgensen N, Andersson  
AM, Krarup T, Keiding N, Skakkebaek NE. High frequency of  
sub-optimal semen quality in an unselected population of young  
men. Human Reproduction. 2000 Feb 1;15(2):366-72.  
74. Jensen TK, Vierula M, Hjollund NH, Saaranen M, Scheike T,  
Saarikoski S, Suominen J, Keiski A, Toppari J, Skakkebæk NE.  
Semen quality among Danish and Finnish men attempting to  
conceive. The Danish First Pregnancy Planner Study Team.  
European Journal of Endocrinology. 2000 Jan 1;142(1):47-52.  
75. Fisch H, Goluboff ET, Olson JH, Feldshuh J, Broder SJ, Barad  
DH. Semen analyses in 1,283 men from the United States over  
a 25-year period: no decline in quality. Fertility and sterility.  
1996 May 1;65(5):1009-14.  
5
5
5
7. Ménézo Y, Dale B, Cohen M. DNA damage and repair in human  
oocytes and embryos: a review. Zygote. 2010 Nov;18(4):357-  
6
5.  
8. Derijck A, van der Heijden G, Giele M, Philippens M, de Boer  
P. DNA double-strand break repair in parental chromatin of  
mouse zygotes, the first cell cycle as an origin of de novo  
76. Carlsen E, Giwercman A, Keiding N, Skakkebæk NE. Evidence  
for decreasing quality of semen during past 50 years. Bmj. 1992  
Sep 12;305(6854):609-13.  
mutation. Human molecular  
8;17(13):1922-37.  
genetics. 2008 Mar  
1
5
9. Carrell DT, Liu L, Peterson CM, Jones KP, Hatasaka HH,  
Erickson L, Campbell B. Sperm DNA fragmentation is  
increased in couples with unexplained recurrent pregnancy loss.  
Archives of andrology. 2003 Jan 1;49(1):49-55.  
77. Auger J, Kunstmann JM, Czyglik F, Jouannet P. Decline in  
semen quality among fertile men in Paris during the past 20  
years. New England Journal of Medicine. 1995 Feb  
2;332(5):281-5.  
306  
Journal of Environmental Treatment Techniques  
2020, Volume 8, Issue 1, Pages: 299-309  
7
7
8. Adamopoulos DA, Pappa A, Nicopoulou S, Andreou E,  
Karamertzanis M, Michopoulos J, Deligianni V, Simou M.  
Andrology: seminal volume and total sperm number trends in  
men attending subfertllity clinics in the greater Athens area  
during the period 19771993. Human Reproduction. 1996 Sep  
without other changes in semen quality. Human Reproduction.  
2005 Jun 24;20(10):2776-83.  
95. Robbins WA, Rubes J, Selevan SG, Perreault SD. Air pollution  
and sperm aneuploidy in healthy young men. Environ  
Epidemiol Toxicol. 1999;1(125ñ131):154.  
96. Moldan B, Schnoor JL. Czechoslovakia: examining a critically  
ill environment. Environmental science & technology. 1992  
Jan;26(1):14-21.  
97. Sram RJ, BeneS I, Binková B, Dejmek J, Horstman D,  
Kotĕsovec F, Otto D, Perreault SD, Rubes J, Selevan SG, Skalík  
I. Teplice program--the impact of air pollution on human health.  
Environmental health perspectives. 1996 Aug;104(suppl  
4):699-714.  
98. Radwan M, Jurewicz J, Polańska K, Sobala W, Radwan P,  
Bochenek M, Hanke W. Exposure to ambient air pollution-does  
it affect semen quality and the level of reproductive hormones?.  
Annals of human biology. 2016 Jan 2;43(1):50-6.  
99. Tamburrino L, Marchiani S, Montoya M, Marino FE, Natali I,  
Cambi M, Forti G, Baldi E, Muratori M. Mechanisms and  
clinical correlates of sperm DNA damage. Asian journal of  
andrology. 2012 Jan;14(1):24.  
1
;11(9):1936-41.  
9. Jouannet P, Ducot B, Feneux D, Spira A. Male factors and the  
likelihood of pregnancy in infertile couples. I. Study of sperm  
characteristics. International journal of andrology. 1988  
Oct;11(5):379-94.  
0. Bartoov B, Eltes F, Pansky M, Lederman H, Caspi E, Soffer Y.  
Estimating fertility potential via semen analysis data. Human  
Reproduction. 1993 Jan 1;8(1):65-70.  
1. AYALA C, STEINBERGER E, SMITH DP. The influence of  
semen analysis parameters on the fertility potential of infertile  
couples. Journal of andrology. 1996 Nov 12;17(6):718-25.  
2. ZINAMAN MJ, BROWN CC, SELEVAN SG, CLEGG ED.  
Semen quality and human fertility: a prospective study with  
healthy couples. Journal of Andrology. 2000 Jan 2;21(1):145-  
8
8
8
5
3.  
8
3. Evenson DP, Jost LK, Marshall D, Zinaman MJ, Clegg E, Purvis  
K, De Angelis P, Claussen OP. Utility of the sperm chromatin  
structure assay as a diagnostic and prognostic tool in the human  
fertility clinic. Human reproduction. 1999 Apr 1;14(4):1039-  
100. Evenson DP, Wixon R. Clinical aspects of sperm DNA  
fragmentation detection and male infertility. Theriogenology.  
2006 Mar 15;65(5):979-91.  
4
9.  
101. Erenpreiss J, Spano M, Erenpreisa J, Bungum M, Giwercman  
A. Sperm chromatin structure and male fertility: biological and  
clinical aspects. Asian journal of andrology. 2006 Jan;8(1):11-  
29.  
102. Bungum M, Humaidan P, Axmon A, Spano M, Bungum L,  
Erenpreiss J, Giwercman A. Sperm DNA integrity assessment  
in prediction of assisted reproduction technology outcome.  
Human reproduction. 2006 Aug 18;22(1):174-9.  
8
8
4. Potts RJ, Newbury CJ, Smith G, Notarianni LJ, Jefferies TM.  
Sperm chromatin damage associated with male smoking.  
Mutation Research/Fundamental and Molecular Mechanisms of  
Mutagenesis. 1999 Jan 25;423(1-2):103-11.  
5. Aitken RJ, De Iuliis GN, Finnie JM, Hedges A, McLachlan RI.  
Analysis of the relationships between oxidative stress, DNA  
damage and sperm vitality in a patient population: development  
of diagnostic criteria. Human Reproduction. 2010 Aug  
103. Ménézo Y, Dale B, Cohen M. DNA damage and repair in  
1
7;25(10):2415-26.  
human oocytes and embryos: a review. Zygote. 2010  
Nov;18(4):357-65.  
8
8
6. Thilagavathi J, Venkatesh S, Dada R. Telomere length in  
reproduction. Andrologia. 2013 Oct 1;45(5):289-304.  
7. Rocca MS, Speltra E, Menegazzo M, Garolla A, Foresta C,  
Ferlin A. Sperm telomere length as a parameter of sperm quality  
in normozoospermic men. Human reproduction (Oxford,  
England). 2016 Jun;31(6):1158-63.  
8. Cariati F, Jaroudi S, Alfarawati S, Raberi A, Alviggi C,  
Pivonello R, Wells D. Investigation of sperm telomere length  
as a potential marker of paternal genome integrity and semen  
quality. Reproductive biomedicine online. 2016 Sep  
104. Rubes J, Rybar R, Prinosilova P, Veznik Z, Chvatalova I,  
Solansky I, Sram RJ. Genetic polymorphisms influence the  
susceptibility of men to sperm DNA damage associated with  
exposure to air pollution. Mutation Research/Fundamental and  
Molecular Mechanisms of Mutagenesis. 2010 Jan 5;683(1-2):9-  
15.  
105. Auger J, Kunstmann JM, Czyglik F, Jouannet P. Decline in  
semen quality among fertile men in Paris during the past 20  
years. New England Journal of Medicine. 1995 Feb  
2;332(5):281-5.  
8
8
1
;33(3):404-11.  
9. Ling X, Zhang G, Chen Q, Yang H, Sun L, Zhou N, Wang Z,  
Zou P, Wang X, Cui Z, Liu J. Shorter sperm telomere length in  
association with exposure to polycyclic aromatic hydrocarbons:  
Results from the MARHCS cohort study in Chongqing, China  
and in vivo animal experiments. Environment international.  
106. Hauser R, Sokol R. Science linking environmental contaminant  
exposures with fertility and reproductive health impacts in the  
adult male. Fertility and sterility. 2008 Feb 1;89(2):e59-65.  
107. Mendiola J, Jørgensen N, Andersson AM, Stahlhut RW, Liu F,  
Swan SH. Reproductive parameters in young men living in  
Rochester, New York. Fertility and sterility. 2014 Apr  
1;101(4):1064-71.  
108. Flanagan JM, Popendikyte V, Pozdniakovaite N, Sobolev M,  
Assadzadeh A, Schumacher A, Zangeneh M, Lau L, Virtanen  
C, Wang SC, Petronis A. Intra-and interindividual epigenetic  
variation in human germ cells. The American Journal of Human  
Genetics. 2006 Jul 1;79(1):67-84.  
109. Hughes IA, Martin H, Jääskeläinen J. Genetic mechanisms of  
fetal male undermasculinization: a background to the role of  
endocrine disruptors. Environmental research. 2006 Jan  
1;100(1):44-9.  
110. Feng S, Jacobsen SE, Reik W. Epigenetic reprogramming in  
plant and animal development. Science. 2010 Oct  
29;330(6004):622-7.  
2
016 Oct 1;95:79-85.  
9
9
0. Vecoli C, Montano L, Borghini A, Notari T, Guglielmino A,  
Mercuri A, Turchi S, Andreassi M. Effects of highly polluted  
environment on sperm telomere length:  
a pilot study.  
International journal of molecular sciences. 2017  
Aug;18(8):1703.  
1. Yang Q, Zhao F, Dai S, Zhang N, Zhao W, Bai R, Sun Y. Sperm  
telomere length is positively associated with the quality of early  
embryonic development. Human reproduction. 2015 Jun  
1
6;30(8):1876-81.  
9
9
2. Berger R. The incidence of constitutional chromosome  
aberrations. Journal de genetique humaine. 1975 Oct;23:42-9.  
3. Shi Q, Martin RH. Aneuploidy in human sperm: a review of the  
frequency and distribution of aneuploidy, effects of donor age  
and lifestyle factors. Cytogenetic and Genome Research.  
111. Skinner MK. Environmental epigenetic transgenerational  
inheritance and somatic epigenetic mitotic stability.  
Epigenetics. 2011 Jul;6(7):838.  
112. Stouder C, Somm E, Paoloni-Giacobino A. Prenatal exposure  
to ethanol: a specific effect on the H19 gene in sperm.  
Reproductive Toxicology. 2011 May 1;31(4):507-12.  
2
000;90(3-4):219-26.  
9
4. Rubes J, Selevan SG, Evenson DP, Zudova D, Vozdova M,  
Zudova Z, Robbins WA, Perreault SD. Episodic air pollution is  
associated with increased DNA fragmentation in human sperm  
307  
Journal of Environmental Treatment Techniques  
2020, Volume 8, Issue 1, Pages: 299-309  
1
1
13. Park CJ, Nah WH, Lee JE, Oh YS, Gye MC. Butyl paraben‐  
induced changes in DNA methylation in rat epididymal  
spermatozoa. Andrologia. 2012 May;44:187-93.  
14. Skinner MK, Manikkam M, Guerrero-Bosagna C. Epigenetic  
transgenerational actions of environmental factors in disease  
etiology. Trends in Endocrinology & Metabolism. 2010 Apr  
133. Somers CM, McCarry BE, Malek F, Quinn JS. Reduction of  
particulate air pollution lowers the risk of heritable mutations in  
mice. Science. 2004 May 14;304(5673):1008-10.  
134. Inyang F, Ramesh A, Kopsombut P, Niaz MS, Hood DB,  
Nyanda AM, Archibong AE. Disruption of testicular  
steroidogenesis and epididymal function by inhaled benzo (a)  
pyrene. Reproductive Toxicology. 2003 Sep 1;17(5):527-37.  
135. Tsukue N, Toda N, Tsubone H, Sagai M, Jin WZ, Watanabe G,  
Taya K, Birumachi JI, Suzuki AK. Diesel exhaust (DE) affects  
the regulation of testicular function in male Fischer 344 rats.  
Journal of toxicology and environmental health Part A. 2001  
May 25;63(2):115-26.  
136. Rolland M, Le Moal J, Wagner V, Royère D, De Mouzon J.  
Decline in semen concentration and morphology in a sample of  
26 609 men close to general population between 1989 and 2005  
in France. Human Reproduction. 2012 Dec 4;28(2):462-70.  
137. Auger J, Kunstmann JM, Czyglik F, Jouannet P. Decline in  
semen quality among fertile men in Paris during the past 20  
years. New England Journal of Medicine. 1995 Feb  
2;332(5):281-5.  
1
;21(4):214-22.  
15. Rajender S, Avery K, Agarwal A. Epigenetics,  
spermatogenesis and male infertility. Mutation  
Research/Reviews in Mutation Research. 2011 May  
;727(3):62-71.  
1
1
1
1
16. Carrell DT. Epigenetics of the male gamete. Fertility and  
sterility. 2012 Feb 1;97(2):267-74.  
17. Dada R, Kumar M, Jesudasan R, Fernández JL, Gosálvez J,  
Agarwal A. Epigenetics and its role in male infertility. Journal  
of assisted reproduction and genetics. 2012 Mar 1;29(3):213-  
2
3.  
1
18. Vrijens K, Bollati V, Nawrot TS. MicroRNAs as potential  
signatures of environmental exposure or effect: a systematic  
review. Environmental health perspectives. 2015 Jan  
1
6;123(5):399-411.  
138. Rosa MD, Zarrilli S, Paesano L, Carbone U, Boggia B, Petretta  
M, Maisto A, Cimmino F, Puca G, Colao A, Lombardi G.  
Traffic pollutants affect fertility in men. Human Reproduction.  
2003 May 1;18(5):1055-61.  
1
1
1
19. Hayashi K. Chuva de Sousa Lopes SM. Kaneda M., Tang F.,  
Hajkova P., Lao K., O'Carroll D., Das PP, Tarakhovsky A.,  
Miska EA, Surani MA. 2008.  
20. Maatouk DM, Loveland KL, McManus MT, Moore K, Harfe  
BD. Dicer1 is required for differentiation of the mouse male  
germline. Biology of reproduction. 2008 Oct 1;79(4):696-703.  
21. Huszar JM, Payne CJ. MicroRNA 146 (Mir146) modulates  
spermatogonial differentiation by retinoic acid in mice. Biology  
of reproduction. 2013 Jan 1;88(1):15-.  
139. Jurewicz J, Hanke W, Radwan M, Bonde J. Environmental  
factors and semen quality. International journal of occupational  
medicine and environmental health. 2009 Jan 1;22(4):305-29.  
140. Deng Z, Chen F, Zhang M, Lan L, Qiao Z, Cui Y, An J, Wang  
N, Fan Z, Zhao X, Li X. Association between air pollution and  
sperm quality:  
A systematic review and meta-analysis.  
1
1
22. Kotaja N. MicroRNAs and spermatogenesis. Fertility and  
sterility. 2014 Jun 1;101(6):1552-62..  
23. Khazaie Y, Esfahani MH. MicroRNA and male infertility: a  
potential for diagnosis. International journal of fertility &  
sterility. 2014 Jul;8(2):113.  
24. Salas-Huetos A, Blanco J, Vidal F, Godo A, Grossmann M,  
Pons MC, Silvia F, Garrido N, Anton E. Spermatozoa from  
patients with seminal alterations exhibit a differential micro-  
ribonucleic acid profile. Fertility and sterility. 2015 Sep  
Environmental pollution. 2016 Jan 1;208:663-9.  
141. Arbak P, Yavuz O, Bukan N, Balbay O, Ulger F, Annakkaya  
AN. Serum oxidant and antioxidant levels in diesel exposed toll  
collectors. Journal of occupational health. 2004;46(4):281-8.  
142. Guven A, Kayikci A, Cam K, Arbak P, Balbay O, Cam M.  
Alterations in semen parameters of toll collectors working at  
motorways: does diesel exposure induce detrimental effects on  
semen?. Andrologia. 2008 Dec;40(6):346-51.  
143. Hammoud A, Carrell DT, Gibson M, Sanderson M, Parker-  
Jones K, Peterson CM. Decreased sperm motility is associated  
with air pollution in Salt Lake City. Fertility and sterility. 2010  
Apr 1;93(6):1875-9.  
144. Somers CM. Ambient air pollution exposure and damage to  
male gametes: human studies and in situ ‘sentinel’animal  
experiments. Systems biology in reproductive medicine. 2011  
Jan 1;57(1-2):63-71.  
145. Sram R. Impact of air pollution on reproductive health.  
146. Wijesekara GU, Fernando DM, Wijerathna S, Bandara N.  
Environmental and occupational exposures as a cause of male  
infertility.  
147. Figà Talamanca I, Cini C, Varricchio GC, Dondero F,  
Gandini L, Lenzi A, Lombardo F, Angelucci L, Di Grezia R,  
Patacchioli FR. Effects of prolonged autovehicle driving on  
male reproductive function: a study among taxi drivers.  
American journal of industrial medicine. 1996 Dec;30(6):750-  
8.  
148. Hansen C, Luben TJ, Sacks JD, Olshan A, Jeffay S, Strader L,  
Perreault SD. The effect of ambient air pollution on sperm  
quality. Environmental health perspectives. 2009 Sep  
18;118(2):203-9.  
149. Hsu PC, Chen IY, Pan CH, Wu KY, Pan MH, Chen JR, Chen  
CJ, Chang-Chien GP, Hsu CH, Liu CS, Wu MT. Sperm DNA  
damage correlates with polycyclic aromatic hydrocarbons  
biomarker in coke-oven workers. International archives of  
occupational and environmental health. 2006 May 1;79(5):349-  
56.  
150. Radwan M, Jurewicz J, Polańska K, Sobala W, Radwan P,  
Bochenek M, Hanke W. Exposure to ambient air pollution-does  
it affect semen quality and the level of reproductive hormones?.  
Annals of human biology. 2016 Jan 2;43(1):50-6.  
1
1
;104(3):591-601.  
1
1
25. Wang C, Yang C, Chen X, Yao B, Yang C, Zhu C, Li L, Wang  
J, Li X, Shao Y, Liu Y. Altered profile of seminal plasma  
microRNAs in the molecular diagnosis of male infertility.  
Clinical chemistry. 2011 Dec 1;57(12):1722-31.  
26. Yoshida S, Sagai M, Oshio S, Umeda T, Ihara T, Sugamata M,  
Sugawara I, Takeda K. Exposure to diesel exhaust affects the  
male reproductive system of mice. International Journal of  
Andrology. 1999 Oct;22(5):307-15.  
27. Watanabe N. Decreased number of sperms and Sertoli cells in  
mature rats exposed to diesel exhaust as fetuses. Toxicology  
letters. 2005 Jan 15;155(1):51-8.  
28. Ieradi LA, Cristaldi M, Mascanzoni D, Cardarelli E, Grossi R,  
Campanella L. Genetic damage in urban mice exposed to traffic  
pollution. Environmental Pollution. 1996 Jan 1;92(3):323-8.  
29. Jeng HA, Yu L. Alteration of sperm quality and hormone levels  
by polycyclic aromatic hydrocarbons on airborne particulate  
particles. Journal of Environmental Science and Health, Part A.  
1
1
1
2
008 Apr 29;43(7):675-81.  
1
1
1
30. Watanabe N, Oonuki Y. Inhalation of diesel engine exhaust  
affects spermatogenesis in growing male rats. Environmental  
health perspectives. 1999 Jul;107(7):539-44.  
31. Somers CM, Yauk CL, White PA, Parfett CL, Quinn JS. Air  
pollution induces heritable DNA mutations. Proceedings of the  
National Academy of Sciences. 2002 Dec 10;99(25):15904-7.  
32. Yauk C, Polyzos A, Rowan-Carroll A, Somers CM, Godschalk  
RW, Van Schooten FJ, Berndt ML, Pogribny IP, Koturbash I,  
Williams A, Douglas GR. Germ-line mutations, DNA damage,  
and global hypermethylation in mice exposed to particulate air  
pollution in an urban/industrial location. Proceedings of the  
National Academy of Sciences. 2008 Jan 15;105(2):605-10.  
308  
Journal of Environmental Treatment Techniques  
2020, Volume 8, Issue 1, Pages: 299-309  
1
51. Gaspari L, Chang SS, Santella RM, Garte S, Pedotti P, Taioli  
E. Polycyclic aromatic hydrocarbon-DNA adducts in human  
sperm as a marker of DNA damage and infertility. Mutation  
Research/Genetic Toxicology and Environmental Mutagenesis.  
2
003 Mar 3;535(2):155-60.  
1
1
52. Sokol RZ, Kraft P, Fowler IM, Mamet R, Kim E, Berhane KT.  
Exposure to environmental ozone alters semen quality.  
Environmental health perspectives. 2005 Oct 5;114(3):360-5.  
53. Rubes J, Selevan SG, Evenson DP, Zudova D, Vozdova M,  
Zudova Z, Robbins WA, Perreault SD. Episodic air pollution is  
associated with increased DNA fragmentation in human sperm  
without other changes in semen quality. Human Reproduction.  
2
005 Jun 24;20(10):2776-83.  
1
1
1
54. Evenson DP, Wixon R. Environmental toxicants cause sperm  
DNA fragmentation as detected by the Sperm Chromatin  
Structure Assay (SCSA®). Toxicology and Applied  
Pharmacology. 2005 Sep 1;207(2):532-7.  
55. Jurewicz J, Radwan M, Sobala W, Polańska K, Radwan P,  
Jakubowski L, Ulańska A, Hanke W. The relationship between  
exposure to air pollution and sperm disomy. Environmental and  
molecular mutagenesis. 2015 Jan;56(1):50-9.  
56. Carré J, Gatimel N, Moreau J, Parinaud J, Léandri R. Does air  
pollution play a role in infertility?: a systematic review.  
Environmental Health. 2017 Dec;16(1):82.  
309