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

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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)


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 )


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


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%;


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.


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

-


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


μ3,P

M2,5pa


,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


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,


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 )


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


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 )


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


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


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


μm,PM2,5pa


,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)


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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