Effects of Smoking on the Placenta
hexachlorobenzeneHCBthanthatofneonatesborntopassive-smokingmothersorto motherswhohavehadnocontactwhatsoeverwithtobaccosmoke
[7] .Diaplacentartrans-
missionoftoxicsubstancesthereforeplaysamajorroleandtherateofadversepregnancy outcomesinwomenwhosmokemaybeashighas33
[8–11] .Syncytialnecrosisand
thickeningofthetrophoblastmembranehavebeendetectedduringtheirstweeksofpreg- nancyintheplacentaofwomenwhosmoke
[12] .Duringthisperiod,stemcellsforthe
formationofthesyncytiumorofcellgroupsfusetogetherandthesebecomeimplantedin theuterus.Accordingtoexperimentalanimalresearch,smokinginterfereswiththesepro-
cesses.Levelsofthemarkerhormones,oestriol,oestradiol,humanchorionicgonadotro- phinhCGandplacentallactogen,arereducedinsmokers
[13–15] .Similarly,theactivity
ofplacentalaromataseisdiminishedbysmoking [16]
.Comparativeinvestigationsofpla- centaltissuefromsmokingandnon-smokingwomensmokingstatusquantiiedobjec-
tivelybythemeasurementsoftissuecotininelevelshaverevealedraisedhaematocritsand cadmiumlevelsintheplacentalbloodofsmokers
[17] .Furthermore,therelativesurface
areasoffoetalcapillariesaswellastherelativeandabsolutevolumesoffoetalcapillaries arereduced,primarilyasaresultofadecreaseinmeancapillarydiameterratherthantotal
capillarylength [17]
.Althoughhaematocritsareincreased,foetusesofsmokingmothers sufferhypoxicstress;overall,itmustbeassumedthatthisisanall-or-noneeffectrather
thanonewhichisdose-dependenti.e.onthenumberofcigarettessmoked [17]
.Inthe irst trimester, the placental volume of smokers is already smaller than that of non-
smokersbecause of resistance of high-perfusion. This state also persists in the second trimester,withtheresultthat3-dimensionalultrasoundcanbeusedtodrawconclusionscon-
cerningsmoking-relatedimpairmentoftrophoblastinvasion [18]
.Womenwhosmokeduring pregnancyhavea2.6-to4.4-foldhigherriskofplacentapraeviathannon-smokers
[19] .
Severalisoenzymsofthecytochromoxygenasesystemoccurnotonlyintheliver,but alsoinseveraltissuessuchastheplacenta.Theactivityofthemonooxygenasesystem
CYP1A1increasesupto100-foldandmoreifthepregnantmotherisasmoker.This enzymeisinducedbypolyaromaticcompounds,butnotbyphenobarbitone
[20–25] .It
couldbedemonstratedthattheactivityofthemonooxygenasesystemisinducedonlybya smokingmotherbutnotbyasmokingfather
[26] .Theextentofinductionwasdependent
onthenumberofcigarettessmokeddaily.Becauseofthelackofenzymeinductioninthe liver,theplacentaseemstoplayamajorroleinprotectingthefoetusfromthetoxic-prod-
uctsoftobaccosmokewhicharedegradedbeforetheyreachthefoetus [27]
. Cadmiumlevelsareelevatedinsmokers
[28,29] ,hCGsecretionisreducedandtropho-
blastproliferationisinhibitedthroughinteractionswithcalmodulin [30]
.Nicotine,Cd
2+
and polyaromatichydrocarbonspossiblyalsoinluenceoestrogensynthesisandmetabolism,as
wellasgranulosa-lutealfunction [31]
.Isolatedstemvillousarteriesfromtheplacentasof womenwhosmokedheavily³15cigarettesdayrespondedinvitrotoendothelin-1bydevel-
opinglowertensioncomparedwithvesselsfromnon-smokers;however,themaximumvaso- constrictiveresponsetoendothelin-1wasmorepronounced
[32] .Itisconcludedfromthese
experimentsthatthemechanicalpropertiesofstemvillousarteriesfromheavysmokersare alteredandthesechangesmayultimatelycompromisefoetalplacentalbloodlowandthereby
contributetolowerbirthweight [32]
. SmokingisassociatedwithincreasedCd
2+
levels,raisedhaematocritandalterationsin theine-tissuestructureoftheplacentasmallerintervillousspaces,reducedfoetalcapillary
volume,leadingtohypoxicstatescharacterisedbydiminishedO
2
transfer [17]
.Placental receptorsforepidermalgrowthfactorEGF,apotentmitogenfortrophoblasts,arereduced
[31, 33–35] . Other investigators have attributed a pivotal harmful role to CO and lead,
alongsidenumerousotherharmfulconstituentsoftobaccosmoke [36]
.Measurementsof cadmium,zincandcopperlevelsintheplacentaltissueofwomenfromFinland,Estoniaand
St.Petersburg [36]
revealthatplacentalconcentrationsofCd
2+
,Cu
2+
andPb
2+
arealready markedlyelevatedintheirsttrimester
[6] ,andanegativecorrelationwasfoundbetween
placentalCu
2+
levelsandneonatalbirthweight [36]
.ThehighestCd
2+
concentrationswere detectedinsamplescollectedfromwomenlivinginSt.Petersburg
[36] .
ThelossofEGFreceptorsbecauseofbenzo[a]pyreneislinkednotonlywithreduced trophoblastproliferationandhCGsecretion
[37] ,butalsowithreducedc-mycexpression
proto-oncogene and increased transforming growth factor TGF b2 expression [38]
. Tobaccosmokeisthereforeabletoexertadeleteriouseffectontrophoblastgeneexpres-
sionviaEGFreceptors,c-mycdown-regulationandTGFb1up-regulation.Trophoblast growthisalsoaffectedbecauseofsmoking-inducedhypoxiaseebelow
[31,39] .
Inhaledtobaccoproductssuchascadmiumandbenzo[a]pyrenearetoxicsubstancesthat actspeciicallyonuterinevilli,contributingtofoetalhypoxemiaandleadingtomiscarriage.