Air pollution from natural and anthropic sources and male ...
Transcript of Air pollution from natural and anthropic sources and male ...
REVIEW Open Access
Air pollution from natural and anthropicsources and male fertilityJoanna Jurewicz1*, Emila Dziewirska1, Michał Radwan2,3 and Wojciech Hanke1
Abstract
Exposure to air pollution has been clearly associated with a range of adverse health effects, including reproductivetoxicity. However, a limited amount of research has been conducted to examine the association between airpollution and male reproductive outcomes, specially semen quality. We performed a systematic review (up toMarch 2017) to assess the impact of environmental and occupational exposure to air pollution on semen quality.Epidemiological studies focusing on air pollution exposures and male reproduction were identified by a search ofthe PUBMED, MEDLINE, EBSCO and TOXNET literature bases. Twenty-two studies were included which assess theimpact of air pollutants (PM2.5, PM10, SO2, NOx, O3, PAHs) on main semen parameters (sperm concentration,motility, morphology), CASA parameters, DNA fragmentation, sperm aneuploidy and the level of reproductivehormones. The number of studies found significant results supporting the evidence that air pollution may affect:DNA fragmentation, morphology and motility.In summary, most studies concluded that outdoor air pollution affects at least one of the assessed semenparameters. However the diversity of air pollutants and semen parameters presented in the studies included in thereview and different study design caused lack of consistency in results and difficulties in comparison.
Keywords: Air pollution, Environmental exposure, Occupational exposure, Semen quality, Male fertility
IntroductionDuring the past decades a possible degradation in hu-man semen quality has been debated intensively and hasbecome an important public health issue. A controver-sial review article of 61 studies analyzing sperm concen-trations in fertile men and in men of unknown fertilitypublished between 1938 and 1990 by Carlsen et al., 1992showed a significant decrease in sperm concentrations(from 113 mln/ml to 66 mln/ml) and in semen volume(from 3.40 ml to 2.75 ml) [1]. Critics suggested thatchanging laboratory methods, statistical issues, heteroge-nicity of populations selected for studies (men of provenfertility or not, different geographical regions and ethnicgroups), bias because of factors such as age and abstin-ence time or inherent variability of sperm counts mighthave affected the findings [2–4]. However more recentanalysis gives further evidence for declining sperm qual-ity. Swan et al., 2000 performed multivariate analysis of
101 studies from 1934 to 1996, taking into accountmany of the confounding factors, reported an evengreater reduction in sperm concentration, indicating anannual decline of 1.5% in the USA compared with the1% previously determined by Carlsen et al., 1992 [5].Over time the World Health Organization has lowered
the accepted values for normal semen parameters(count, motility and morphology) because in the last de-cades those parameters have consistently decreased evenin healthy men [6]. It has been suggested that this de-crease in semen quality is associated with the observeddecrease in fertility [7].This has raised new concerns about environmental
factors such as exposure to pollutants or toxicants, and life-style factors such as smoking, heat, stress, obesity and sex-ual behaviours which might affect human fertility [8–11].Air pollutants can be in the form of solid particles, li-
quid droplets, or gases. In addition, they may be naturalor man-made. Sources of air pollution refer to the vari-ous locations, activities or factors which are responsiblefor the releasing of pollutants into the atmosphere. Par-ticulate matter (PM) in the respirable range (PM2.5) is of
* Correspondence: [email protected] of Environmental Epidemiology, Nofer Institute of OccupationalMedicine, 8 Teresy St, 91-362 Lodz, PolandFull list of author information is available at the end of the article
© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Jurewicz et al. Reproductive Biology and Endocrinology (2018) 16:109 https://doi.org/10.1186/s12958-018-0430-2
particular interest, because it can carry multiple trace ele-ments and polycyclic aromatic hydrocarbons (PAHs), agroup of compounds that include several endocrine dis-ruptors which may affect both the hypothalamic pituitaryaxis and testicular spermatogenesis and have the potentialfor causing sperm alterations [12, 13].Ambient air pollution has been associated with a var-
iety of health effects including cardiovascular [14] andrespiratory diseases [15], adverse pregnancy outcome orimpaired neurodevelopment in children [16]. However, alimited amount of research has been conducted toexamine the association between air pollution and malereproductive outcomes, specifically semen quality.The aim of this review was to assess current evidence
regarding the impact of air pollution on male fertility.
Materials and methodsEpidemiological studies focused on the exposure to air pol-lution and male fertility were identified by a search of thePubMed, Medline and Ebsco literature databases (beforeMarch 2017). The search combined terms referring to out-door air pollution and male fertility. The combination offollowing key words was used: 1) referred to the exposure:exposure to air pollutants: PM2.5, PM10, SO2, NOx, O3,polycyclic aromatic hydrocarbons (PAHs); 2) referred tooutcome: main semen parameters (sperm concentration,motility, morphology), CASA (Computer-Assisted SpermAnalysis) parameters (VAP (average path velocity), VSL(straight velocity), VCL (curvilinear velocity), ALH (ampli-tude of lateral displacement of the sperm head, LIN (linear-ity), BCF (beat-cross frequency), STR (path straightness),DNA fragmentation, sperm aneuploidy and the level ofreproductive hormones.From each study, the following information was ab-
stracted: authors, the year published, the year studied,study design, population demographics, results, the mainconclusions, exposure and methods used for its assess-ment (including biomarkers) and confounding factors.We included cohort, case-control and cross-sectionalstudies that analyzed the impact of outdoor air pollut-ants on male fertility in humans. The studies with expos-ure to most commonly assessed air pollutants: PM2.5,PM10, SO2, NOx, O3, PAHs were included. As just a fewstudies evaluated different air pollutants e.g. lead orcadmium those studies were not included in thepresent review. We excluded studies that analyzed theeffects of air pollution on pregnancy outcome as wellas those assessing the effects of lifestyle factors (smok-ing, alcohol consumption, caffeine intake). Also studiesfocused on animal research, in vitro studies and reviewpapers were excluded. We limited the language only toEnglish and we included only peer-review originalarticles.
Data were independently extracted by two investiga-tors, who determined eligibility. Discrepancies were re-solved by intervention of a third independent author. Ifmultiple published reports from the same study wereavailable, only the one with the most detailed informa-tion was included. All pertinent reports were retrievedand the relative reference lists were systematicallysearched in order to identify any potential additionalstudies that could be included.
ResultsIn our initial search (up to March 2017) a total of 250studies were retrieved in the initial electronic search. Ofthese, 210 were excluded by abstract because werefocused on the animal research, were concentrated onmolecule level or the study was a review according tothe exclusion criteria described above, leaving 30 articlesfor inclusion in our analysis. Nine of the studies wereexcluded because the full text was not in English andbecause it was a review article or meta-analysis. Thetotal of 22 articles were included. Remaining articleswere excluded because did not assess outdoor air pollu-tion (mainly indoor air pollution). Details of the studiesincluded in the review are presented in Table 1.
Summary of collected dataEnvironmental exposure to air pollutantsMain semen parameters (motility, morphology, spermconcentration)Thirteen studies examine the association between mainsemen parameters and environmental outdoor air pollu-tion [17–29]. Three studies were performed in USA[18–20], five in China [21, 22, 27–29] and two in Poland[23, 24] and in Czech Republic [17, 26] and one in Italy[25]. In six of the presented studies the study populationwas recruited from general population [17, 19, 21, 22, 25,26]. The level of PAHs were analyzed in four studies[22, 24, 28, 29] in urine [24, 28, 29] and blood [22].In the study performed in Czech Republic the authors
noticed that men exposed to air pollution were more likelyto have lower percentage of motile sperm (β = − 8.12;95%CI: -12.95, − 3.30) and lower percentage of sperm withnormal morphology (β = − 0.84; 95%CI: -1.15, − 0.53)(fewer sperm with normal morphology or normal headshape) than were those lived in a city with less air pollu-tion [17]. Later study among the same participants did notfind the association between high air pollution and spermconcentration, volume, motility and morphology [26]. TheAuthors concluded that the inconsistency between studiescould be due to differences in the exposures.In the study in Los Angeles, California environmental
exposure to ozone (O3) was associated with lower spermconcentration (p < 0.01) [18]. The ozone exposure wasalso associated with decrease in sperm concentration
Jurewicz et al. Reproductive Biology and Endocrinology (2018) 16:109 Page 2 of 18
Table
1Detailsof
thestud
iesinclud
edin
thereview
Source
Locatio
nPerio
dStud
ypo
pulatio
nAge
ofmen
Type
ofstud
yExpo
sure
(rang
emin-m
ax)
Outcome
Environm
entalexposure
Santi,et
al.2016[25]
Italy,
Mod
ena
Nov
2014
toFeb2015
406men
from
theClinical
Patholog
yof
theNuo
voOsped
aleCivile
Sant
Ago
stinoEstense(NOCSA
E)
32.3±5.2
Retrospe
ctivecoho
rtstud
yPM
10(4–155
μg/m
3 )Vo
lume,concen
tration(×
106 /mL),total
sperm
numbe
r,typical/atypicalforms
(%),progressive
motility
(%),no
n-prog
ressivemotility
(%),totalm
otility
(%),leucocytes
PM2.5(1–101
μg/m
3 )
Wu,et
al.2016[27]
China,
Wuh
anMarch
2013
toDec
2015
1759
men
,partnersof
wom
enun
dergoing
assisted
reprod
uctive
techno
logy
34.4±5.4
Retrospe
ctivecoho
rtstud
yPM
10(67.2–197μg
/m3 )
Con
centratio
n(×
106 /mL),spe
rmcoun
t,totalm
otility
(%),prog
ressive
motility
(%),
PM2,5(27.3–172.4μg
/m3 )
Radw
an,etal.2016[23]
Poland
,Lodz
Jan2008
toApr
2011
327men
from
infertility
clinic
32.3±4.4
Cross-sectio
nal
PM10
(11.78–120.5μg
/m3 )
Con
centratio
n(×
106 /mL),m
otility
(%),
sperm
with
abno
rmalmorph
olog
y(%),
DFI(%),HDS(%),CASA
parameters:VSL,
VCL,LIN;FSH
,E2,T
PM2.5(7.99–93.89μg
/m3 )
SO2(9.12–167.9μg
/m3 )
CO(0.15–1.85
μg/m
3 )
NOx(2.17–215.14
μg/m
3 )
Jurewicz,et
al.2015[34]
Poland
,Lodz
–212men
from
infertility
clinic
22–57
Cross-sectio
nal
PM10
(11.59–122.8μg
/m3 )
Sperm
aneuploidy,spe
rmconcen
tration
(×10
6 /mL),totalmotility
(%),abno
rmal
morph
olog
y(%)
32.25±5.72
PM2,5(7.99–95.22μg
/m3 )
O3(12.33–79.75
μg/m
3 )
SO2(10.11–160.90μg
/m3 )
CO(0.17–1.79
μg/m
3 )
NOx(2.32–218.30
μg/m
3 )
Radw
an,etal.2015[35]
Poland
,Lodz
Jan2008
toApr
2011
181men
from
infertility
clinic
32.1±4.6
Cross-sectio
nal
1PA
Hmetabolitesin
urine
1-OHP(0.04–2.03
μg/g
creat)
Sperm
aneuploidy,spe
rmconcen
tration
(×10
6 /mL),totalmotility
(%),no
rmal
sperm
morph
olog
y(%),
Zhou
,etal.2014[21]
China,
Cho
ngqing
2007
1346
men
from
family
planning
institu
tions
20–40
Cross-sectio
nal
PM10
(66–160.5μg
/m3 )
Volume,concen
tration(×
106 /mL),
prog
ressivemotility
(%),totalm
otility,
morph
olog
y(normalform
s%),CASA
sperm
motility
parameters(VCL,VSL,
VAP,BC
F,ALH
,LIN,STR)
SO2(31-101μg
/m3 )
NO2(19.5–53.5μg
/m3 )
Jurewicz,et
al.2013[24]
Poland
,Lodz
–277men
from
infertility
clinic
32±4.6
Cross-sectio
nal
1PA
Hmetabolite
inurine
1-OHP(0.02–2.03
μg/g
creat)
Volume,concen
tration(×
106 /mL),
motility
(%),atypicalsperm
(%),static
sperm
(%),CASA
parameters:VA
P,VSL,
VCL,BC
F,ALH
,DFI(%)
Song
,etal.2013[22]
China,Pearl
RiverDelta
Jul2010to
Aug
2011
53men
from
infertility
clinic
Cross-sectio
nal
16PA
Hsin
bloo
dCon
centratio
n(×
106 /mL),volum
e,motility
(grade
A,g
rade
B,gradeC)
Han,etal.2011[31]
China,
Cho
ngqing
Dec
2007
232men
from
Cho
ngqing
Family
Planning
Research
Institu
te
31.89±5.53
Cross-sectio
nal
4PA
Hmetabolitesin
urine
Apo
ptoticmarker(Ann
exin
V−/PI−
spermatozoa
%,A
nnexin
V+/PI−
spermatozoa
%,PI+spermatozoa
%,
comet
parameters(tail%,taillen
gth,
TDM)
1-OHP(μg/gcreatin
ine)
9-OHPh
(μg/gcreatin
ine)
2-OHFIu(μg/gcreatin
ine)
Jurewicz et al. Reproductive Biology and Endocrinology (2018) 16:109 Page 3 of 18
Table
1Detailsof
thestud
iesinclud
edin
thereview
(Con
tinued)
Source
Locatio
nPerio
dStud
ypo
pulatio
nAge
ofmen
Type
ofstud
yExpo
sure
(rang
emin-m
ax)
Outcome
2-OHNa(μg/gcreatin
ine)
Ham
mou
d,et
al.2010
[20]
USA
,Salt
Lake
City
2002
to2007
1699
semen
analyses
and877inseminations
32.8±6.57
Ecolog
icalstud
yPM
2.5(5-24μg
/m3 )
Motility,con
centratio
n(×10
6 /mL),
morph
olog
y(normalform
s%)
Hansen,et
al.2010[19]
USA
,Wake
Cou
nty,
Shelby
Cou
ntyand
Galveston
Cou
nty
2002
to2004
228men
,partnersof
preg
nant
wom
en18–40
Cross-sectio
nal
O3(2–83.2pp
b)Con
centratio
n(×
106 /mL),cou
nt,
morph
olog
y(normalform
s%),
abno
rmalmorph
olog
y(%),abno
rmal
head
(%),abno
rmalmidsection(%),
abno
rmaltail(%),cytoplasmicdrop
lets
(%),CMA(%),DFI(%)
PM2.5(2.1–62.7μg
/m3 )
Xia,et
al.2009a
[28]
China,
Nanjing
March
2004
toJul2007
513infertile
men
and
273fertile
men
ascontrols
28.65±4.51
forinfertile
males
and
29.32±4.51
forcontrols
Cross-sectio
nal
4PA
Hmetabolitesin
urine
Volume,concen
tration(×10
6 /mL),
sperm
numbe
rpe
rejaculum
,spe
rmmotility
1-N(μg/gcreat)
2-N(μg/gcreat)
1-OHP(μg/gcreat)
2-OHF(μg
/gcreat)
Xia,et
al.2009b
[29]
China,
Nanjing
March
2004
toJul2007
542men
No
inform
ation
-based
onabstract
Cross-sectio
nal
4PA
Hmetabolitesin
urine
Volume,concen
tration(×
106 /mL),
sperm
numbe
rpe
rejaculum
,spe
rmmotility
1-N(μg/gcreat)
2-N(μg/gcreat)
1-OHP(μg/gcreat)
2-OHF(μg
/gcreat)
Rube
s,et
al.2007[32]
Czech,
Teplice
Sep1995
toSep1997
36men
19–21
Long
itudinalstudy
SO2(μg/m
3 )%DFI,G
STM1ge
notype
NOx(μg/m
3 )
PM10
(16.9–76.3μg
/m3 )
PAH(21.4–221.9ng
/m3 )
Sokol,et
al.2006[18]
USA
,Los
Ang
eles
Jan1996
toDec
1998
48sperm
dono
rsfro
msperm
dono
rbank
19–35mean
25.3±4.7
Retrospe
ctivecoho
rtstud
yO3(1.69–47.51pp
b)Con
centratio
n(×10
6 /mL),m
otility
(×10
6 )NO2(9.04–79.80pp
b)
CO(0.37–3.86
ppm)
PM10
(6.84–101.88
μg/m
3 )
Rube
s,et
al.2005[26]
Czech,
Teplice
Sep1995
toSep1997
36men
19–21
Prospe
ctivecoho
rtstud
ySO
2(μg/m
3 )Cou
nt,con
centratio
n(×10
6 /mL),
volume,motility
(%),no
rmalsperm
head
morph
olog
y(%),no
rmal
morph
olog
y(%),straight
linevelocity,
curviline
arvelocity,linearity,%DFI
NOx(μg/m
3 )
PM10
(μg/m
3 )
PAH(ng/m
3 )
Selevan,et
al.2000[17]
Czech,
Teplice,
Prachatice
1993
to1994
408men
from
Hygiene
Station
18Prospe
ctivecoho
rtstud
yPM
10(3.1–832.0μg
/m3 )
Semen
volume,concen
tration(×10
6 /mL),totalcoun
t,motility
(%),total
prog
ressive,no
rmalmorph
olog
y(%),
norm
alhe
ads(%),VSL,VC
L,LIN,spe
rmchromatin
structure
SO2(1–697.9μg
/m3 )
CO(0–5.50mg/m
3 )
NOx(0–367.20μg
/m3 )
Jurewicz et al. Reproductive Biology and Endocrinology (2018) 16:109 Page 4 of 18
Table
1Detailsof
thestud
iesinclud
edin
thereview
(Con
tinued)
Source
Locatio
nPerio
dStud
ypo
pulatio
nAge
ofmen
Type
ofstud
yExpo
sure
(rang
emin-m
ax)
Outcome
Robb
ins,et
al.1999[33]
Czech,
Teplice,
Prachatice
Subset
of32
men
No
inform
ation
-based
onabstract
Prospe
ctivecoho
rtstud
yNoinform
ation-basedon
abstract
Sperm
aneuploidy
Occup
ationalexposure
Calog
ero,et
al.2011
[37]
Italy
1.)15June
to15July2.)1
to31Jan
36men
working
atmotorway
tollgates;
32un
expo
sedmen
28–4737.1
±5.5
Cross-sectio
nal
NOx(μg/m
3 )LH
,FSH
,T,spe
rmconcen
tration(×10
6 /mL),totalcoun
t,totalm
otility
(%),
prog
ressivemotility
(%),no
rmalform
s(%),sperm
chromatin
integrity,D
FI(%)
SOx(μg/m
3 )
Bogg
ia,etal.2009[38]
Italy
2000
to2004
307men
working
atmotorway
23–57mean
37.16
Cross-sectio
nal
NO2(μg/m
3 )FSH,LH,T,spe
rmcoun
t,motility
(%),
morph
olog
y,
Guven
,etal.2008[36]
Turkey
–38
men
working
atmotorway
and35
men
working
atofficeas
acontrolg
roup
35.2±6.4
(study
grou
p)and
33.7±6.7
(con
trol
grou
p)
Cross-sectio
nal
Traffic
pollutantsmainly
thediesel
Con
centratio
n(×10
6 /mL),m
otility,
morph
olog
y
DeRo
sa,etal.2003[39]
Italy
Jan2
000to
Jan2
002
85men
working
atmotorway
and85
control
men
rand
omlyselected
;
38.6±0.8
(study
grou
p)and
39.6±0.7
(con
trol
grou
p)
Cross-sectio
nal
CO(9-27mg/m
3 )FSH,LH,T,spe
rmcoun
t,volume,
motility,m
orph
olog
y,sperm
mem
brane
functio
n,forw
ardprog
ression,sperm
kine
tics:VSL,VC
L,LIN,A
LH,
NO(58–398mg/m
3 )
SO(9–27μg
/m3 )
Pb(0.9–4.2μg
/m3 )
PM10
particulatematter<10
μm,PM2,5pa
rticulatematter<2,5μm
,O3ozon
e,SO
xsulphu
roxides,C
Ocarbon
mon
oxide,
NOxnitrog
enoxides,P
AHpo
lycyclicarom
atichy
drocarbo
ns,1
-OHP1-hy
droxyp
yren
e,Pb
lead
,Cd–cadm
ium,1
-N1-hy
droxyn
apthalen
e,2-N2-hy
droxyn
apthalen
e,1-OHP1-hy
droxyp
yren
e,2-OHF2-hy
droxyfluoren
e,VC
Lcurviline
arvelocity,V
SLstraight
linevelocity,V
APaverag
epa
thvelocity,B
CFbe
atcross
freq
uency,ALH
amplitu
deof
lateralh
eaddisplacemen
ts,%
DFIpe
rcen
tage
ofsperm
with
frag
men
tedDNA,%
HDShigh
DNAstaina
bility,LINlin
earity,STRstraightne
ss,g
rade
Asperm
with
prog
ressivemotility,g
rade
Bno
nlinearmotility,g
rade
cno
n-prog
ressivemotility,TDM
taildistrib
uted
mom
ent,%CM
Ape
rcen
tage
ofsperm
chromatin
maturity
,LHluteinizingho
rmon
e,FSHfollicle-stim
ulatingho
rmon
e,Ttestosterone
,E2estrad
iol
Jurewicz et al. Reproductive Biology and Endocrinology (2018) 16:109 Page 5 of 18
and count. Whereas exposure to PM2.5 increase the per-centage of sperm cells with cytoplasmic drop and abnor-mal heads (but only in basic model without adjusting forpotential confounding factors) in the study performed inUnited States by Hansen and co-workers (2010) [19].Hammoud et al., 2010 in study conducted in Salt LakeCity, Utah, found a negative association between PM2.5
and sperm motility and sperm head morphology (p = 0.010and p = 0.044 respectively) [20].In urban and rural areas in China the study performed
among 1346 volunteers observed that the concentrationof PM10, SO2 and NO2 were negatively associated withnormal sperm morphology percentage (p < 0.001) [21].The next study in China noticed a significant negativerelation between semen motility and the concentration ofPAHs (polycyclic aromatic hydrocarbons) in blood among53 infertile volunteers (p < 0.01) [22]. The next studyamong 1759 men undergoing assisted reproductive tech-nology procedures also performed in China found that ex-posure to PM2.5 was inversely associated with spermconcentration (β = − 0.20; (95%CI: -0.34, − 0.07) and count(β = − 0.22; 95%CI: -0.35, − 0.08) [27].Santi et al., 2016 in Italian study observed that PM2.5
was directly related to total sperm number (p < 0.001).PM10 was directly related to both semen volume (0 <0.001), and typical forms (p < 0.001), inversely related toatypical forms (p < 0.001), but related neither to spermconcentration (p = 0.430) nor to sperm motility [25].Also Radwan et al., 2016 observed statistically significantassociation between abnormalities in sperm morphologyand exposure to air pollutants (PM10, PM2.5, SO2, NOX,CO) (p = 0.0002, p = 0.0001, p = 0.0001, p = 0.01, p =0.0001, respectively) [23]. Additionally exposure toPM10, PM2.5, CO was negatively associated with the levelof testosterone (p < 0.05) [23]. The next study performedin Poland among the same men from infertility clinic ex-amined the association between a biomarker of exposureto polycyclic aromatic hydrocarbons (1-hydroksypyrene(1-OHP)) and semen quality [24]. A positive relationwas found between the level of 1-OHP in urine andsperm neck abnormalities (p = 0.001) as well as the per-centage of static sperm cells and the level of 1-OHP de-creased semen volume and motile sperm cells (p =0.018) [24]. Human studies among patients from infertil-ity clinics in China showed that subjects with higherurinary concentrations of 1-OHP, 2-hydroxyfluorene(2-OHF) and sum PAH metabolites (assessed as tertiles)were more likely to have idiopathic male infertility(p-value for trend 0.034, 0.022 and 0.022, respectively)[28]. Higher idiopathic infertility risk was found in thegroup of idiopathic infertile subjects with abnormalsemen quality when two groups of idiopathic infertilesubjects with different semen quality [28]. In the nextstudy by the same authors Xia et al., 2009b was found
that men with higher 1-OHP (assessed as quintiles) weremore likely to have below-reference sperm concentrationand sperm number per ejaculum [29].
CASA parametersThe CASA parameters were assessed only in 5 studies[17, 21, 23, 24, 26] this is probably because of the factthat CASA has not been applied widely in field studiesbecause the logistics of recording the sample promptly(to avoid degradation of sperm motility over time) andcontrolling the temperature precisely are challenging inthe field studies [30]. Zhou and co-workers 2014 ob-served inverse associations between sperm VCL (curvi-linear velocity) and VSL and the PM10, SO2, NO2 (p <0.001) [21]. Whereas Selevan et al., 2000 did not demon-strate any consistent negative associations between thequality of sperm motion and periods of high air pollu-tion [17]. Rubes et al., 2005 in the same study populationalso did not observe any statistically significant associ-ation [26]. No association between CASA parameters:VSL, VCL, LIN and exposure to PM10, PM2.5, SO2, NOX,CO [23] and the level of 1-OHP in urine [24] was alsonoticed the in the study performed in Poland.
DNA fragmentationSeven studies assess the exposure to air pollution andsperm chromatin structure [17, 19, 23, 24, 26, 31, 32].Two of them [24, 31] assess the exposure to polycyclicaromatic hydrocarbons, using biomarkers of exposure. Inmost of the studies SCSA method was used to evaluatesperm DNA, only Han et al., 2011 [31] used TUNELmethod. Men exposed to air pollution in Teplice region(Czech Republic) had more sperm with abnormal chroma-tin than those lived in a Prachatice with less air pollution(p < 0.05) [17]. In the group of the same men fromTeplice, high air pollution exposure was associated withincreased sperm DNA fragmentation (β = 0.19; 95%CI:0.02–0.36) [26]. The next study performed by the sameauthors found an evidence for a gene-environment inter-action between glutathione-S transferase M1 (GSTM1)and air pollution (presumably c-PAHs) [32]. This study re-vealed a statistically significant association betweenGSTM1 null genotype and increased percentage of spermwith fragmented DNA (%DFI) (β = 0.309; 95% CI: 0.129,0.489) [32]. Furthermore, GSTM1 null men also showedhigher %DFI in response to exposure to intermittent airpollution (beta = 0.487; 95% CI: 0.243, 0.731) [32].The association between urinary polycyclic aromatic
hydrocarbon metabolites and sperm DNA damage wasexamined among 232 men from general population inChina [31]. The increased urinary 2-hydroxynaphthalene(2-OHNa) levels were associated with increased cometparameters including the percentage of DNA in the tail(%tail), tail length and tail distribution (β = 13.26%;
Jurewicz et al. Reproductive Biology and Endocrinology (2018) 16:109 Page 6 of 18
95%CI: 7.97–18.55; β = 12.25; 95%CI: 0.01–24.52; β =7.55; 95%CI: 1.28–18.83 respectively). Whereas the urin-ary level of 1-hydroxypyrene was associated only withincreased tail% (β = 5.32; 95%CI: 0.47–10.17) [31]. In thestudy in Poland Radwan et al., 2016 found that exposureto PM2.5 and PM10 increase the percentage of cells withimmature chromatin (HDS) (p = 0.002, p = 0.0001, re-spectively), but no the DNA fragmentation index (DFI)[23]. Whereas in the study in the same population urin-ary levels of 1-OHP was not associated with DNA frag-mentation index in sperm (DFI) [24]. Also Hansen andco-worker 2010 did not observe any statistically signifi-cant relation between PM2.5 and O3 and DNA integrityand chromatin maturity [19].
Sperm aneuploidyThe first study which examined the association betweenexposure to air pollution and sperm aneuploidy was per-formed by Robbins et al., 1999 who collected a subset ofsamples (n = 32) from a larger epidemiological investiga-tion of air pollution and reproductive health [33]. Thesex chromosomal aneuploidy, YY, was found to befive-fold higher in sperm following periods of exposureto high air pollution (as indicated by SO2 levels = 196.9mug/m3) as compared to low exposure (SO2 = 32.0mug/m3) (IRR = 5.25, 95%CI: 2.5,11.0) [33].The study with larger sample size of 212 men who were
attending an infertility clinic for diagnostic purposes inPoland found positive associations between exposure toPM2.5 and disomy Y (p = 0.001), sex chromosome disomy(p = 0.05) and disomy 21 (p = 0.03). Exposure to PM10 wasassociated with disomy 21 (p = 0.02) [34]. Conversely, ex-posure to ozone, CO, SO2, and NOx did not affect spermaneuploidy [34]. The study performed among the samestudy population observed that level of 1-OHP in urine in-crease the total sex-chromosome disomy (p = 0.03) andchromosome-18 disomy (p = 0.03) [35].On the other hand Rubes et al., 2005 did not find any as-
sociation between exposure to periods of high air pollutionand total aneuploidy among young men from Teplice [26].
Occupational exposure to air pollutantsMain semen parameters (motility, morphology, spermconcentration)One of the study which investigate the effects of trafficpollutants, mainly the diesel exposure on semen parame-ters was performed in Turkey among 38 men working astoll collectors at motorways and 35 men working as of-fice personnel [36]. The differences regarding the abnor-mal sperm count and motility were significant betweenthe groups (p = 0.002 and p = 0.003, respectively). Simi-larly, the ratio of sperm cells with normal morphologywas significantly lower in the study group than that inthe control group (p = 0.001) [36]. The adverse role of
traffic pollutants on male fertility was also investigatedin the study among 36 men working at motorway toll-gates and 32 unexposed healthy men [37]. Sperm con-centration, total sperm count, total and progressivemotility, and normal forms were significantly lower inthese men compared with controls (p < 0.05) [37]. Alsomale workers, employed in a motorway company occu-pationally exposed to NO2 had a significant lower spermtotal motility than in not exposed workers (p < 0.05)[38]. Total motility, forward progression were signifi-cantly lower in tollgate workers versus controls in thestudy performed in Italy (p < 0.0001) [39].
CASA parametersOnly one study assess the occupational exposure to airpollution and CASA parameters [39]. Motorway tollgateworkers had significantly lower the CASA parameters:VSL, VCL, LIN, ALH (amplitude of lateral head dis-placements) compared with age-matched men living inthe same area (p < 0.0001) [39].
DNA fragmentationMotorway tollgate workers had a significantly higherpercentage of spermatozoa with damaged chromatin andDNA fragmentation, a late sign of apoptosis, comparedwith controls (p < 0.001) in the study performed by Calo-gero et al., 2011 [37]. In this study the sperm DNA wasevaluated using two methods: SCSA and TUNEL.
Level of reproductive hormonesLuteinizing hormone (LH), follicle-stimulating hormone(FSH), and testosterone (T) serum levels were within thenormal range in tollgate workers compared to controls inthe two studies performed in Italy [37, 39]. Serum levelsof LH and FSH the study performed by Calogero et al.,2011 [37] were (2.9 ± 0.7 (1.9–4.5) IU/l and 4.2 ± 1.1 (1.9–7.1) IU/l for cases and 3.2 ± 1.1 (1.5–6.5) IU/l and 4.3 ± 1.5(2.4–7.1) IU/l for controls respectively). Whereas in thesecond Italian study the levels of reproductive hormoneswere as follows: LH (IU/l) 2.8 ± 0.2 (0.7–8.9) for cases 2.8± 0.1 (0.9–5.4) for controls, FSH and serum testosterone(μg/l) 4.1 ± 0.3 (0.7–13.5) and 4.8 ± 0.2 (2.3–9.2) respect-ively for cases and 3.2 ± 0.2 (0.9–6.3) and 4.7 ± 0.2(2.9–10.8) respectively for controls [39].
DiscussionThis review shows that air pollution (environmental andoccupational) may affect semen quality. All the papersincluded in the review reported significant associationwith at least one of the examined semen parameters(Table 2). Number of studies found a significant resultssupporting the evidence that air pollution may affect:DNA fragmentation, morphology and motility.
Jurewicz et al. Reproductive Biology and Endocrinology (2018) 16:109 Page 7 of 18
Table
2Expo
sure
toairpo
llutantsandsemen
quality
Outcome
Airpo
llutio
n
PM10
PM2,5
Pb,C
dNOx
SOx
PAHs
O3
CO
Ehou
stpartciles
-diesel
Volume
Santi2016+↑
Zhou
2014
-Ru
bes2007
-Ru
bes2005
-
Santi2016-
Zhou
2014
-Ru
bes2007
-Ru
bes2005
-
Zhou
2014
-Ru
bes2007
-Ru
bes2005
-
Song
2013
-Han
2011
-Ru
bes2007
-Jurewicz2013
+↑
Con
centratio
n(×10
6 /mL)
Santi2016-
Zhou
2014
+↑
Rube
s2007
-Ru
bes2005
-Wu2016
+↓
Sokol2006-
Santi2016-
Wu2016
+↓
Ham
mou
nd2010
-Hansen2010
-
Zhou
2014
-Ru
bes2007
-Ru
bes2005
-Sokol2006-
Calog
ero2011
+↓
Zhou
2014
-Ru
bes2007
-Ru
bes2005
-Calog
ero2011
+↓
Song
2013
-Han
2011
-Ru
bes2007
-Xia2009b+↓
Hansen2010
-Sokol2006+↓
Sokol2006-
Sperm
coun
tSanti2016-
Sokol2006-
Rube
s2005
-Wu2006
+↓
Santi2016+↑
Wu2016
+↓
Hansen2010
-
Sokol2006-
Rube
s2005
-Calog
ero2011
+↓
Bogg
ia2009
-
Rube
s2005
-Calog
ero2011
+↓
Han
2011
-Xia2009b+↓
Hansen2010
-Sokol2006-
Guven
2008
+↓
Morph
olog
y(%
ofsperm
with
norm
almorph
olog
y)(%)
Santi2016+↑
Zhou
2014
+↓
Rube
s2007
-Selevan2000
+↓
Radw
an2016
+↓
Santi2016-
Ham
mou
nd2010
-Hansen2010
–Radw
an2016
+↓
Zhou
2014
+↓
Rube
s2007
-Selevan2000
+↓
Calog
ero2011
+↓
Bogg
ia2009
–Radw
an2016
+↓
Zhou
2014
+↓
Rube
s2007
-Selevan2000
+↓
Calog
ero2011
+↓
Radw
an2016
+↓
Han
2011
–Ru
bes2007
–Jurewicz2013
+↓
Hansen2010
–Radw
an2016
+↓
Selevan2000
+↓
Guven
2008
+↓
Prog
ressive
motility
(%)
Santi2016-
Wu2016
-Zh
ou2014
-Selevan2000
+↓
Santi2016-
Wu2016
-Zh
ou2014
-Selevan2000
+↓
Calog
ero2011
+↓
Zhou
2014
-Selevan2000
+↓
Calog
ero2011
+↓
Selevan2000
+↓
Totalm
otility
(%)
Santi2016–
Wu2016
-Zh
ou2014
-Ru
bes2007
–Sokol2006-
Rube
s2005
-Selevan2000
+↓
Santi2016–
Wu2016
-Ham
mou
nd2010
+↓
DeRo
sa2003
+↓
Zhou
2014
-Ru
bes2007
-Sokol2006-
Rube
s2005
-Selevan2000
+↓
Calog
ero2011
+↓
Bogg
ia2009
+↓
DeRo
sa2003
+↓
Zhou
2014
-Ru
bes2007
-Ru
bes2005
-Selevan
2000
+↓
Calog
ero2011
+↓
DeRo
sa2003
+↓
Song
2013
+Han
2011
-Ru
bes2007
-Jurewicz2013
+↑
Sokol2006-
Sokol2006
-Selevan
2000
+↓
DeRo
sa2003
+↓
Guven
2008
+↓
Sperm
DNA
damage
Rube
s2007
+↑
Rube
s2005
+Zh
ou2014
+↑
Selevan2000
+Rawdan2016
+↓
Hansen2010
-Radw
an2016
-Ru
bes2007
+↑
Rube
s2005
+Zh
ou2014
+↑
Selevan2000
+Calog
ero2011
+↓
Radw
an2016
-DeRo
sa2003
+↓
Rube
s2007
+↑
Rube
s2005
+Zh
ou2014
+↑
Selevan2000
+Calog
ero2011
+↑
Radw
an2016
–DeRo
sa2003
+↓
Rube
s2007
+↑
Rube
s2005
+Han
2011
+↑
Jurewicz2013
+
Hansen2010
-Sokol2006+↑
Selevan2
000+
Rawdan2016
-
Jurewicz et al. Reproductive Biology and Endocrinology (2018) 16:109 Page 8 of 18
Table
2Expo
sure
toairpo
llutantsandsemen
quality
(Con
tinued)
Outcome
Airpo
llutio
n
PM10
PM2,5
Pb,C
dNOx
SOx
PAHs
O3
CO
Ehou
stpartciles
-diesel
Sperm
aneuploidy
Jurewicz2015
+↑
Jurewicz2015
+↑
Robb
ins1999
+↑
Radw
an2015
+↑
Reprod
uctive
horm
ones
Radw
an2016
+↑
Radw
an2016
+↑
DeRo
sa2003
-Calog
ero2011
-Bo
ggia2009
-DeRo
sa2003
-
Calog
ero2011
-DeRo
sa2003
-DeRo
sa2003
-Radw
an2016
+↑
PM10
particulatematter<10
μ3,P
M2,5pa
rticulatematter<2,5μm
,Pblead
,Cdcadm
ium,N
Oxnitrog
enoxides,SOxsulfu
rdioxide,
PAHpo
lycyclicarom
atichy
drocarbo
ns,O
3ozon
e,CO
carbon
mon
oxide
+sign
ificant
association;
−no
nsign
ificant
association;
↑increase;↓
decrease
Jurewicz et al. Reproductive Biology and Endocrinology (2018) 16:109 Page 9 of 18
Other review studies on exposure to air pollutants andmale fertility also indicated the link between air pollutionand sperm motility [40], sperm DNA fragmentation andmorphology [41]. Deng et al., 2016 [42] in the meta-analyisfound an evidence that ambient air polluation could altersperm parameters resulting in infertility. Additionally sev-eral animal toxicological studies have provided evidencethat exposure to air pollutants could damage the testiclesand impact on sperm quality and fertility [43].
Adjustment for confoundersDetails of the potential risk factors are shown in Table 3.The results of the presented studies were adjusted forwell-known confounders such as abstinence period (daysbefore semen collection), age, smoking status and drink-ing. In some studies the smoking status was confirmedby the measure of the cotinine level in saliva or urine[23, 24, 34]. Several studies also considered the caffeineintake [17], season [17, 23, 24, 26, 34], temperature [18],BMI [19, 21] and ethnicity [18, 19]. Other factors wereadjusted in some studies, such as vitamin [19], past dis-eases [23, 24, 34] and work posture [38].The major potential confounders in studies of expos-
ure to air pollution and semen quality are well-knownand most studies at least try to assess them. The con-cern is generally in the factors which are unmeasuredsuch as stress or family support. Although available con-founders were taken into account in the statistical ana-lysis there is still possibility that residual or unmeasuredconfounding factors partly contributed to the observedassociation.
Assessment of exposureIn most of the presented studies the exposure assessmentwas based on the information from monitoring stationsfor a specific period of time (90 days) before semen sam-pling (Table 1). Arithmetic mean for period of 90 days be-fore semen collection was calculated as indicator ofexposure. The process of spermatogenesis involves a seriesof complex steps (stem cell replication, meiosis, and sper-miogenesis) over approximately 74 days in humans [44].An exposure period of approximately 90 days is generallyaccepted as being of sufficient duration for detecting ef-fects on any stage of spermatogeneis when using semenmeasures as the biologic end points [17].The biomarkers of exposure was used in 6 of the pre-
sented studies. One of those studies were conducted inoccupational settings and measured lead in the bloodand methemoglobin as a marker of NO2, sulphemoglo-bin for SO2, carboxyhemoglobin and zinc propophyrin.In case of environmental exposure PAH metaboliteswere measured in urine in five studies [22, 24, 28, 29,31]. Han et al., 2011 [31] and Xia et al., 2009a [28], Xiaet al., 2009b [29] have assessed urinary level of four PAH
metabolites whereas Jurewicz et al., 2013 [24] assessedonly 1-hydroksypirene (1-OHP). Song et al., 2013 mea-sured 16 PAHs levels in blood and semen [22].
Differences in the results between studiesThere are possibly numerous factors contributing to thedivergent results between the studies. The various end-points of semen quality (sperm concentration, motility,morphology, sperm DNA damage, sperm aneuploidy)used may be a possible explanation for the differentstudy results. The use of different biomarkers to ascer-tain exposure or the exposure estimation based on theinformation from the monitoring station may have somebearing on the statistical association. Also different levelof exposure to air pollutants may impact on the differ-ences between studies. The choice of covariates for stat-istical models may also impact the results. Further issueis a possibility of concomitant exposure to other envir-onmental or occupational factors which may also havean impact on semen quality. Other potential explana-tions for the differences among studies include the typeand timing of exposure, dose, measurement of the ex-posure or an outcome.
Biological mechanismA limited number of animal toxicologic studies haveprovided preliminary evidence of associations betweenexposure to air pollutants and semen quality outcomes.Associations have been observed between total air pollu-tion and reduced daily sperm production in mice andrats receiving in utero or prenatal exposure to totaldiesel exhaust and filtered exhaust [45]. The biologicalmechanisms linking ambient air pollution to decreasedsperm quality have yet to be determined. Sokol et al.,2006 identified several possible mechanisms, includingO3-induced oxidative stress, inflammatory reactions, andthe induction of the formation of circulating toxic spe-cies [18]. Rubes et al., 2007 concluded that the reactivemetabolites of PM10 can reach the testes and react withsperm DNA to form adducts; this toxic effect occurs inlate spermatogenesis, when there are no repair mechan-ism to correct it, resulting in increased DNA fragmenta-tion [32]. Additionally Hammound et al., 2010 suggestthat PM2.5 could act as an endocrine disruptor affectinglate synthesis of proteins necessary for sperm motility[20]. Additionally the reactive oxygen species damagethe integrity of DNA in the sperm nucleus which mayaffect sperm count and motility [46, 47].Rubes et al., 2007 found that men who are homozy-
gous null for GSTM1 have lower capacity to detoxify re-active metabolites of carcinogenic polycyclic aromatichydrocarbons and are consequently more susceptible tothe effects of air pollution on sperm chromatin [32].Also polymorphism in other repair genes (XRCC1,
Jurewicz et al. Reproductive Biology and Endocrinology (2018) 16:109 Page 10 of 18
Table
3Theresults
ofthestud
ieson
airpo
llutio
nandmalefertility
Source
Expo
sure
assessmen
tOutcomemeasured
Con
foun
ders
Statisticalanalysis
Mainfainding
sLimitatio
nsStreng
ths
Santi,et
al.
2016
[25]
PM10
(μg/m
3 )Vo
lume,concen
tration
(×10
6 /mL),totalnu
mbe
r,typicalforms(%),atypical
form
s(%),prog
ressive
motility
(%),no
n-prog
ressivemotility
(%),
totalm
otility
(%),
leucocytes
Tempe
rature,hum
idity
Bivariate
and
multivariate
logistic
regression
mod
els
PM2.5was
directlyrelated
tototalspe
rmnu
mbe
r(p
=0.001);PM10
was
directly
relatedto
semen
volume
(p<0.001)
andtypical
form
s(p<0.001),inversely
relatedto
atypicalform
s(p
< 0.001)
Noinform
ationabou
tsm
oking;
DailyPM
expo
sure
registered
throug
hthemon
itorin
gne
tworkof
thequ
ality
oftheairforthe
province
ofMaden
a;the
relatio
nshipbe
tween
environm
entalP
Mand
semen
quality
was
evaluatedirrespe
ctiveof
thelife-styleandrisk
factorsof
each
men
Thecoho
rtishigh
lyrepresen
tativeof
theen
tire
popu
latio
n;Cho
osingthe
coldestseason
oftheyear
inthisarea
(the
possible
negativeinfluen
ceof
high
ambien
ttemp.
onsperm
quality
was
exclud
ed);
PM2.5(μg/m
3 )
Wu,et
al.2016
[27]
PM10
(μg/m
3 )Con
centratio
n(×10
6 /mL),
sperm
coun
t,totalm
otility
(%),prog
ressivemotility
(%),
Age
,BMI,ethn
ic,
education,sm
oking,
drinking
,abstin
ence,
season
,average
ambien
ttempe
rature
Multivariate
linear
mixed
mod
els
PM2.5was
inversely
associated
with
sperm
concen
tration(β=−0.20;
(95%
CI:−
0.34,−
0.07)and
sperm
coun
t(β=−0.22;
95%CI:−0.35,−
0.08);PM
10was
inverselyassociated
with
sperm
concen
tration
andcoun
t(p<0.05)
Theused
ofam
bien
tPM
expo
suresas
aproxyfor
individu
alexpo
sures;No
investigationof
the
associationbe
tween
expo
sure
andsperm
morph
olog
y;theresults
cann
otbe
directly
gene
ralized
topo
pulatio
nsin
which
PMexpo
sure
levelsare
toolow;Participants
from
infertility
clinic
Bigsamplesize;A
wideconcen
tration
rang
eof
PMexpo
sure;the
use
ofIDW
interpolationto
moreprecisely
estim
ateindividu
alPM
expo
sure;the
non-linear
expo
sure-respo
nse
relatio
nships
PM2.5(μg/m
3 )
Radw
an,etal.
2016
[23]
PM10
Con
centratio
n(×
106 /mL),
motility
(%),sperm
with
abno
rmalmorph
olog
y(%),
DFI(%),HDS(%),CASA
parameters:VSL,VC
L,LIN;
FSH,E
2,T
Age
,smoking,
tempe
rature
(men
from
90days),past
disease,tim
eof
sexual
abstinen
ce,season
Multivariate
linear
regression
Expo
sure
toairpo
llutants
(PM10,PM2,5,SO
2,NOx,
CO)increasedthe
abno
rmalities
insperm
morph
olog
y(p=0.0002,p
=0.0001,p
=0.0001,p
=0.01,p
=0.0001,
respectively);N
egative
associationwerefoun
dbe
tweenairpo
llutantsand
testosterone
levels(p<
0.05);Therewereapo
sitive
associations
betw
eenPM
10andPM
2,5andHDS(p=
0.002,p=0.0001,
respectively)
participantsfro
man
infertility
clinic;single
semen
sample;expo
sure
levelsassessed
byconsideringtheZIP
code
ofeach
participants;
Assessm
entof
manydifferent
semen
parameters,
reprod
uctive
horm
ones
levels
andsperm
chromatin
structure;
detailed
questio
nnaire
inform
ationallowed
forcontrol
confou
ndingfactors
intheanalysis;
cotin
inemeasured
insalivato
verified
smokingstatus;
PM2.5
SO2
CO
NOx
Jurewicz,et
al.
2015
[34]
PM10
(μg/m
3 )Sperm
aneuploidy,spe
rmconcen
tration(×10
6 /mL),
totalm
otility
(%),abno
rmal
morph
olog
y(%)
Age
,smoking,
drinking
,tempe
rature,season,
pastdisease,
abstinen
ceinterval,
distance
from
mon
itorin
gstation,
concen
tration,motility,
multivariate
analysis
Therewas
apo
sitive
associationbe
tween
expo
sure
toPM
2.5and
disomyY(p=0.001),sex
chromosom
edisomy(p=
0.05),disomyof
chromosom
e21
(p=0.03);
Expo
sure
levelsassessed
byconsideringtheZIP
code
ofeach
participants;p
articipants
from
aninfertility
clinic;
sing
lesemen
sample;
Manyconfou
nders
includ
edto
the
analysis;cotinine
measuredin
saliva
toverifiedsm
oking
status;d
etailed
questio
nnaire
PM2.5(μg/m
3 )
O3(μg/m
3 )
SO2(μg/m
3 )
CO(μg/m
3 )
Jurewicz et al. Reproductive Biology and Endocrinology (2018) 16:109 Page 11 of 18
Table
3Theresults
ofthestud
ieson
airpo
llutio
nandmalefertility
(Con
tinued)
Source
Expo
sure
assessmen
tOutcomemeasured
Con
foun
ders
Statisticalanalysis
Mainfainding
sLimitatio
nsStreng
ths
morph
olog
y,PM
10,
SO2
xposureto
PM10
was
associated
with
disomy21
(p=0.02)
inform
ationallowed
forcontrol
confou
ndingfactors
intheanalysis,
NOx(μg/m
3 )
Radw
an,etal.
2015
[35]
1PA
Hmetabolite
inurine(1-OHP)
Sperm
aneuploidy,spe
rmconcen
tration(×
106 /mL),
totalm
otility
(%),no
rmal
sperm
morph
olog
y(%),
Abstin
ence,age
,sm
oking,
season
,pastdisease,
Multivariate
analysis
Positiveassociations
betw
eenlevelo
f1-OHPin
urineandtotalsex-
chromosom
edisomy(p=
0.03);Anincrease
inthefre
quen
cyof
disomy18
was
relatedto
thelevelo
f1-
OHPin
urine(p=0.03)
participantsfro
man
infertility
clinic;single
semen
sample;on
ebiom
arkerof
PAHs
expo
sure-1-
hydroksypyrene
(1-OHP)
cotin
inemeasured
insalivato
verified
smokingstatus;
detailed
questio
nnaire
inform
ationallowed
forcontrol
confou
ndingfactors
intheanalysis,
Zhou
,etal.
2014
[21]
PM10
(μg/m
3 )Vo
lume,concen
tration
(×10
6 /mL),p
rogressive
motility
(%),totalm
otility,
morph
olog
y(normalform
s%),CASA
sperm
motility
parameters(VCL,VSL,VA
P,BC
F,ALH
,LIN,STR)
Age
,edu
catio
n,sm
oking,
drinking
,BM
I,abstinen
ce,
season
,
Multivariate
regression
mod
els
PM10,SO2,NO2were
negativelyassociated
with
ano
rmalsperm
morph
olog
ype
rcen
tage
(p<0.001);the
rewereinverse
associations
betw
een
sperm
VCLandVSLvalue
andPM
10,SO2,NO2(p<
0.001);PM10
was
positively
associated
with
sperm
concen
tration(p=0.031)
Usedof
mon
itorin
gdata
forthestud
ysitesto
measure
ambien
tair
pollutio
n;the
measuremen
tand
pred
ictio
nof
PM10,SO2,
NO2expo
sure
were
perfo
rmed
outside;the
used
onlyasing
lesemen
sample
Bigsamplesize;
Expo
sure
toair
pollutantsin
both
urbanandrural
areas;Theuseof
meanconcen
tration
ofeach
pollutant
durin
gthe90
days
before
sampling;
Manyconfou
nders
includ
ingto
the
analyses
SO2(μg/m
3 )
NO2(μg/m
3 )
Jurewicz,et
al.
2013
[24]
1PA
Hmetabolite
inurine(1-OHP)
Volume,concen
tration
(×10
6 /mL),m
otility
(%),
atypicalsperm
(%),static
sperm
(%),DFI(%),CASA
parameters:VA
P,VSL,VC
L,BC
F,ALH
,
Age
,smoking,
past
disease,season
,sexual
abstinen
ce,
Multivariate
regression
mod
els
Apo
sitiveassociations
were
observed
betw
eenthelevel
of1-OHPin
urineand
sperm
neck
abno
rmalities
(p=0.001)
andane
gative
betw
eenthesemen
vol
ume(p=0.014),%
motility
(p=0.0001)and%static
sperm
(p=0.018);
Participantsfro
man
infertility
clinic;single
urineandsemen
sample;on
ebiom
arker
ofPA
Hsexpo
sure-1-
hydroksypyrene
(1-OHP)
cotin
inemeasured
insalivato
verified
smokingstatus;
detailed
questio
nnaire
inform
ationallowed
forcontrol
confou
ndingfactors
intheanalysis,
Song
,etal.
2013
[22]
16PA
Hsin
bloo
dCon
centratio
n(×
106 /mL),
volume,motility
(grade
A,
gradeB,gradeC)
–ThePearsoncorrelation
analysis
Sign
ificant
correlations
betw
eenPA
Hsin
bloo
dandsemen
motility
were
observed
(p<0.01)
Smallsam
plesize;
participantsfro
minfertility
clinic;N
oinvestigationof
the
associationbe
tween
PAHexpo
sure
and
semen
morph
olog
y;
16PA
Hmetabolites
asabiom
arkersof
expo
sure
toPA
H;
Han,etal.2011
[31]
4PA
Hmetabolites
inurine
Apo
ptoticmarker(Ann
exin
V−/PI−spermatozoa
%,
Ann
exin
V+/PI−
spermatozoa
%,PI+
spermatozoa
%,com
etparameters(tail%,tail
leng
th,TDM)
Age
,BMI,abstinen
ce,
smoking,
drinking
,grilled
andsm
oked
food
singe
stions
Multivariate
regression
mod
els
2-OHNalevelswere
associated
with
increased
comet
parameters
includ
ingtail%
(β=13.26%
perlogun
it2-OHNa;
95%CI:7.97–18.55),tail
leng
th(β=12.25;95%CI:
Sing
leurinesample;the
useof
biom
arkersdidn
’tallow
forde
term
ination
ofprim
aryexpo
sure
sources;
Urin
aryPA
Hmetabolitesas
biom
arkersof
PAH
expo
sure;A
ssessing
4metabolites
individu
ally;
Participants
1-OHP
9-OHPh
2-OHFIu
Jurewicz et al. Reproductive Biology and Endocrinology (2018) 16:109 Page 12 of 18
Table
3Theresults
ofthestud
ieson
airpo
llutio
nandmalefertility
(Con
tinued)
Source
Expo
sure
assessmen
tOutcomemeasured
Con
foun
ders
Statisticalanalysis
Mainfainding
sLimitatio
nsStreng
ths
0.01–24.52)a
ndtaildistrib
utio
n(β=7.55;95%
CI:1.28–
18.83);1-OHPwas
associ
ated
with
increasedtail%
(β=5.32;95%
CI:0.47–
10.17);urin
aryPA
Hmetabo
lites
wereassociated
with
decreasedvitalA
nnexin
Vne
gativesperm
coun
t;
recruitedon
lydu
ringthewinter
whe
nairpo
llutio
nishigh
er);many
confou
nders
includ
ingin
the
analyses;
2-OHNa
Ham
mou
d,et
al.2010[20]
PM2.5(μg/m
3 )Motility,con
centratio
n(×10
6 /mL),m
orph
olog
y(normalform
s%)
Tempe
rature,season
Multivariate
regression
mod
els
PM2.5was
negatively
associated
with
sperm
motility
2mon
thsand
3mon
thsfollowingthe
recordingof
thePM
2.5
values
(p=0.010andp=
0.044,respectively)
Participantsfro
mandrolog
ylabo
ratory;
occupatio
nalexposure
didn
’tinclud
ein
the
analysis
Repe
ated
semen
samples;b
igsample
size;The
analyses
ofdaily
levelsof
PM2.5
over
the5years;
Hansen,et
al.
2010
[19]
O3(ppb
)Con
centratio
n(×
106 /mL),
coun
t,morph
olog
y(normal
form
s%),abno
rmal
morph
olog
y(%),abno
rmal
head
(%),abno
rmal
midsection(%),abno
rmal
tail(%),cytoplasmic
drop
lets(%),CMA(%),DFI
(%)
Age
,abstin
ence,
educationlevels,
smoking,
season
,tempe
rature
Multivariate
regression
mod
els
Expo
suresto
O3or
PM2.5
atleastbe
low
thecurren
tNationalA
mbien
tAir
QualityStandardswereno
tassociated
with
decrem
ents
insperm
outcom
es.
Smallsam
plesize;single
semen
sample;
Manyconfou
nders
includ
ingin
the
analysis;
PM2.5(μg/m
3 )
Xia,et
al.2009a
[28]
4PA
Hmetabolitesin
urine
Volume,concen
tration
(×10
6 /mL),spe
rmnu
mbe
rpe
rejaculum
,spe
rmmotility
Age
,abstin
ence
time,
Logisticregression
analysis
Men
with
high
erurinary
concen
trations
of1-OHP,
2-OHPandSum
PAHme
tabo
lites
weremorelikely
tohave
idiopathicmalein
fertility
(pfortren
d=0.034)
Sing
lesemen
sample;
Noinvestigationof
the
associationbe
tween
PAHexpo
sure
and
semen
morph
olog
y;
Bigsamplesize;
Urin
aryPA
Hmetabolitesas
biom
arkersof
PAH
expo
sure;m
enwith
idiopathicinfertility
weredivide
dinto
‘normal’and
‘abn
ormal’sem
enqu
ality
grou
p
1-N
2-N
1-OHP
2-OHF
Xia,et
al.
2009b[29]
4PA
Hmetabolites
inurine
Volume,concen
tration
(×10
6 /mL),spe
rmnu
mbe
rpe
rejaculum
,spe
rmmotility
Noinform
ation-based
onabstract
Noinform
ation-based
onabstract
Men
with
high
er1-OHP
(assessedas
quintiles)were
likelyto
have
below-
referencesperm
concen
tra
tionandsperm
numbe
rpe
rejaculum
.
Noinform
ation-based
onabstract
Noinform
ation-
basedon
abstract
1-N
2-N
1-OHP
2-OHF
Rube
s,et
al.
2007
[32]
SO2(μg/m
3 )%DFI
GSTM1ge
notype
Smoking
Mixed
mod
els
Associatio
nbe
tween
GSTM1nu
llge
notype
and
increased%DFI(beta=
0.309;95%
CI:0.129,0.489).
Smallsam
plesize;
Sing
lesemen
sample;
onlyon
econfou
nder
Noveleviden
cefor
age
ne-
environm
ent
interactionbe
tween
NOX(μg/m
3 )
PM10
(μg/m
3 )
Jurewicz et al. Reproductive Biology and Endocrinology (2018) 16:109 Page 13 of 18
Table
3Theresults
ofthestud
ieson
airpo
llutio
nandmalefertility
(Con
tinued)
Source
Expo
sure
assessmen
tOutcomemeasured
Con
foun
ders
Statisticalanalysis
Mainfainding
sLimitatio
nsStreng
ths
Furthe
rmore,GSTM1nu
llmen
also
show
edhigh
er%DFIin
respon
seto
expo
sure
tointerm
itten
thigh
airpo
llutio
n(beta=
0.487;95%
CI:0.243,0.731)
includ
edto
theanalysis;
GSTM1andair
pollutio
n;PA
H(ng/m
3 )
Sokol,et
al.
2006
[18]
O3(ppb
)Con
centratio
n(×10
6 /mL),
motility
(×10
6 )Tempe
rature,
season
ality,age
ofdo
natio
n,date
ofbirth
Line
armixed
-effects
mod
elNeg
ativeassociation
betw
eenozon
eandsperm
concen
tration(p<0.01);
Smallsam
plesize;N
oinvestigationof
the
associationbe
tweenair
pollutio
nexpo
sure
and
semen
morph
olog
y;
Repe
ated
semen
samples;
NO2(ppb
)
CO(ppm
)
PM10
(μg/m
3 )
Rube
s,et
al.
2005
[26]
SO2(μg/m
3 )Cou
nt,con
centratio
n(×
106 /mL),volum
e,motility
(%),no
rmalsperm
head
morph
olog
y(%),no
rmal
morph
olog
y(%),straight
linevelocity,curvilinear
velocity,linearity,DFI%
Smoking,
drinking
,caffeine,abstinen
ce,
fever,briefs,
Mixed
mod
elsfor
repe
ated
measures
Sign
ificant
association
betw
eenhigh
airpo
llutio
nand%DFI(β=0.19;95%
CI:
0.02–0.36);O
ther
semen
measureswereno
tassociated
with
air
pollutio
n;
Smallsam
plesize;
Urin
esamplewere
assayedforcotin
ine
toconfirm
self-
repo
rted
smoking
status;Blood
sam
plewas
collected
foranalysisof
lead,
mercury
andcad
mium
asan
indica
tionof
possibleex
posure
tometals;
Airpo
llutio
ncate
gorized
aslow
and
high
;sem
ensam
ples
classifyas
a“w
inter”or
“sum
mer”sample
NOx(μg/m
3 )
PM10
(μg/m
3 )
PAH(ng/
m3 )
Selevan,et
al.
2000
[17]
PM10
(μg/m
3 )Semen
volume,
concen
tration(×10
6 /mL),
totalcou
nt,m
otility
(%),
totalp
rogressive,normal
morph
olog
y(%),no
rmal
heads(%),VSL,VC
L,LIN,
sperm
chromatin
structure
Abstin
ence,w
earin
gbriefs,caffeine,high
fever,workand
hobb
ieswith
metal,
workandho
bbieswith
solven
ts,season
Multivariate
regression
mod
els
Sign
ificant
associations
betw
eenmed
ium
air
pollutio
nand%motile
sperm
(β=−8.12;95%
CI:
−12.95,−3.30);be
tween
med
ium
airpo
llutio
nand
prog
ressivemotility
(β=
−0.15;95%
CI:−0.30,−
0.01);
Neg
ativeassociation
betw
eenmed
ium
andhigh
airpo
llutio
nand%no
rmal
morph
olog
y(β=−0.42;
95%CI:−0.69,−
0.14
andβ
=−0.84;95%
CI:−1.15,−
0.53);Highairpo
llutio
nwas
associated
with
parameters
ofsperm
motion–VSL,
VCL,LIN(p<0,005)
Sing
lesemen
sample;
Dataabou
tairpo
llutio
nfro
mtheairmon
itorin
gprog
ram;
Airpo
llutio
ncatego
rized
aslow,
med
ium
andhigh
;Manyconfou
nders
includ
edto
the
analysis
SO2(μg/m
3 )
CO(m
g/m
3 )
NOx(μg/m
3 )
Robb
ins,et
al.
1999
[33]
SO2
aneuploidy
Alcoh
ol,caffeine
intake,fever,laboratory
Poissonregression
mod
eling
Thesexchromosom
alaneuploidy
YYwas
Noinform
ation-based
onabstract
Noinform
ation-
basedon
abstract
Jurewicz et al. Reproductive Biology and Endocrinology (2018) 16:109 Page 14 of 18
Table
3Theresults
ofthestud
ieson
airpo
llutio
nandmalefertility
(Con
tinued)
Source
Expo
sure
assessmen
tOutcomemeasured
Con
foun
ders
Statisticalanalysis
Mainfainding
sLimitatio
nsStreng
ths
variables
associated
with
expo
sure
tohigh
airpo
llutio
nIRR=
5.25,95%
CI:2.5,11.0
Occup
ationalexposure
Calog
ero,et
al.
2011
[37]
NOx(μg/m
3 )LH
,FSH
,T,spe
rmconcen
tration(×10
6 /mL),
totalspe
rmcoun
t,total
motility,p
rogressive
motility
(%),no
rmalform
(%),sperm
chromatin
integrity;D
FI(%)
Age
,len
gthof
occupatio
nalexposure,
smoking
Multivariate
regression
mod
els;
Motorway
tollgateworkers
hadasign
ificantlyhigh
er%spermatozoa
with
damagechromatin
(p<
0.001)
comparedwith
controls,likew
isethe
%spermatozoa
with
fragm
entedDNA;latesign
ofapop
tosiswas
also
sign
ificantlyhigh
erin
tollgateworkers(p<0.001);
sperm
concen
tration,total
sperm
coun
t,totaland
prog
ressivemotility,and
norm
alform
were
sign
ificantlylower
intollgateworkerscompared
with
controls(p<0.05)
Smallsam
plesize;
bloo
dlevelsof
MHb,
SHb,
COHb,
Pbas
abiolog
ical
biom
arkersof
environm
ental
pollutio
n;theair
pollutio
nwas
measuredwith
specificanalyzers
24h/dayfor
30days
durin
gsummer;
SOx(μg/m
3 )
Bogg
ia,etal.
2009
[38]
NO2(μg/m
3 )FSH,LH,T,spe
rmcoun
t,motility,m
orph
olog
y,Fuelcombu
stiongases
Neg
ativeassociation
betw
eenmen
occupatio
nally
expo
sedto
NO2andtotalm
otility
(p<
0.05)
Noindividu
alestim
ations
ofexpo
sure;
Cross-sectio
nal
design
Guven
,etal.
2008
[36]
diesel
Con
centratio
n(×10
6 /mL),
motility,m
orph
olog
y–
stud
ent’s
t-test,M
ann-
Whitney
U-test;
Thedifferences
regarding
theabno
rmalsperm
coun
tandmotility
were
sign
ificant
betw
eenthe
stud
ygrou
pandcontrol
grou
p(p=0.002andp=
0.003,respectively);the
ratio
ofsperm
cells
with
norm
almorph
olog
ywas
sign
ificantlylower
inthe
stud
ygrou
p(p=0.001)
Smallsam
plesize;N
oindividu
alestim
ations
ofexpo
sure;
Cross-sectio
nal
design
Jurewicz et al. Reproductive Biology and Endocrinology (2018) 16:109 Page 15 of 18
Table
3Theresults
ofthestud
ieson
airpo
llutio
nandmalefertility
(Con
tinued)
Source
Expo
sure
assessmen
tOutcomemeasured
Con
foun
ders
Statisticalanalysis
Mainfainding
sLimitatio
nsStreng
ths
DeRo
sa,etal.
2003
[39]
CO(m
g/m
3 )FSH,LH,T,spe
rmcoun
t,volume,motility,
morph
olog
y,sperm
mem
branefunctio
n,forw
ardprog
ression,sperm
kine
tics:VSL,VC
L,LIN,A
LH,
stud
ent’s
t-test;linearre-
gression
analysis
Totalm
otility,forward
prog
ression,functio
naltest
andsperm
kine
ticwere
sign
ificantlylower
intollgateworkersvs.con
trols
(p<0.0001)
Smallsam
plesize;N
oindividu
alestim
ations
ofexpo
sure
bloo
dlevelsof
MHb,
SHb,
COHb,
Pb,Znas
abiolog
ical
biom
arkersof
environm
ental
pollutio
n;
NO(m
g/m
3 )
SO(μg/m
3 )
Pb(μg/m
3 )
PM10
particulatematter<10
μm,PM2,5pa
rticulatematter<2,5μm
,O3ozon
e,SO
xsulphu
roxides,C
Ocarbon
mon
oxide,
NOxnitrog
enoxides,P
AHpo
lycyclicarom
atichy
drocarbo
ns,1
-OHP1-hy
droxyp
yren
e,Pb
lead
,Cd–cadm
ium,1
-N1-hy
droxyn
apthalen
e,2-N2-hy
droxyn
apthalen
e,1-OHP1-hy
droxyp
yren
e,2-OHF2-hy
droxyfluoren
e,VC
Lcurviline
arvelocity,V
SLstraight
linevelocity,V
APaverag
epa
thvelocity,B
CFbe
atcross
freq
uency,ALH
amplitu
deof
lateralh
eaddisplacemen
ts,%
DFIpe
rcen
tage
ofsperm
with
frag
men
tedDNA,%
HDShigh
DNAstaina
bility,LINlin
earity,STRstraightne
ss,g
rade
Asperm
with
prog
ressivemotility,g
rade
Bno
nlinearmotility,g
rade
cno
n-prog
ressivemotility,TDM
taildistrib
uted
mom
ent,%CM
Ape
rcen
tage
ofsperm
chromatin
maturity
,LHluteinizingho
rmon
e,FSHfollicle-stim
ulatingho
rmon
e,Ttestosterone
,E2estrad
iol,
MHbmetha
haem
oglobin,
SHbsulpha
haem
oglobin,C
OHbcarboxyh
aemog
lobin,
IDW
interpolationinversedistan
ceweigh
ting(She
pard’smetho
d)
Jurewicz et al. Reproductive Biology and Endocrinology (2018) 16:109 Page 16 of 18
XPD6, XPD23) and observe an association with high ormedium DNA sperm damage [48].
Strength and limitations of the studiesThe studies presented in this review are mostlywell-design and adjusted for potential confounders(Table 3).The limitation is the exposure assessment approach
based on the information regarding air pollution frommonitoring stations in the limitation in most of thereviewed studies. This is incapable of providing truly in-dividual estimates of exposure. Individual’s precise ex-posure to any component of air pollution would beexpected to depend on his location, activity patterns andthe weather conditions. Additionally in most of the stud-ies single semen samples were collected. Only Sokol etal., 2006 [18] and Hammound et al., 2010 [20] collectedmultiple semen samples, which is relevant consideringthe known high intraindividual variability in semen qual-ity. Also in most of the studies there is no informationabout co-exposure. The next limitation arise from thefact that in most of the selected studies assessing the en-vironmental exposure examined the semen samplesamong men from infertility clinic.
ConclusionsIn conclusion we have found that exposure to air pollu-tion may affect semen quality, especially sperm DNAdamage, morphology and motility. The diversity of thesemen parameters used in the studies and different ap-proach in exposure assessment made the comparison ofthe results difficult. Future research should use a bettercharacterization of exposure models in order to validatethe effects of air pollution on human sperm. Prospectivestudies in well-defined cohorts of men in various popu-lations are needed to evaluate the potential effect of airpollution on male reproductive health. These studiesshould take into account other factors which may inter-fere with male reproductive health. Future studiesshould incorporate different seasons to generate a moreaccurate and full assessment of adverse effect of air pol-lution on male fertility.
Abbreviations%DFI: percentage of sperm with fragmented DNA; %tail: percentage of DNAin the tail; 1-OHP: 1-hydroxypyrene; 2-OHF: 2-hydroxyfluorene; 2-OHNa: 2-hydroxynaphthalene; ALH: amplitude of lateral head displacements;FSH: follicle-stimulating hormone; GSTM1: glutathione-S transferase M1;HDS: high DNA stainability; LH: luteinizing hormone; LIN: linearity;NOx: nitrogen oxides; O3: ozone; PAHs: polycyclic aromatic hydrocarbons;PM: particulate matter; PM10: particulate matter < 10 μm; PM2.5: particulatematter < 2.5 μm; SO2: sulphur dioxide; VCL: curvilinear velocity; VSL: straightline velocity
AcknowledgementsNot applicable.
Ethic approval and consent to participateNot applicable.
Consent for publicationsNot applicable.
Availability of data and materialAll data are included in this article.
FoundingWe did not receive any findings for this study.
Author’s contributionsJJ, ED, MR, WH conducted the literature searchers, selected the studies to beincluded and extracted the data; JJ drafted the manuscript. All authorsprovided substantial intellectual contributions and approved the final versionof the manuscript.
Competing interestsThe author declare that they have no competing interest.
Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.
Author details1Department of Environmental Epidemiology, Nofer Institute of OccupationalMedicine, 8 Teresy St, 91-362 Lodz, Poland. 2Department of Gynecology andReproduction, “Gameta” Hospital, 34/36 Rudzka St, 95-030 Rzgów, Poland.3Faculty of Health Sciences, The State University of Applied Sciences in Plock,2 Dąbrowskiego Sq, 09-402 Płock, Poland.
Received: 18 May 2017 Accepted: 24 October 2018
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