Endocrine-Disrupting Contaminants and Their Effects on Reproductive and Developmental Health - Environmental Contamination: Health Risks and Ecological Restoration - page 53

maternal.oral.exposure.to.bisphenol.A.shifted.the.coat.color.distribution.in.
mouse.offspring.by.decreasing.CpG.methylation.in.the. Agouti .gene.(Dolinoy.
et. al.. 2007).. Although. such. observations. are. evident. of. the. adverse. effects.
caused.by.EDs,.the.mechanistic.role.of.EDs.in.the.modiication.of.epigenome.
remains.largely.not.known.(Crews.and.McLachlan.2006).
Since. DNA. methylation. and. chromatin. patterning. is. programmed. dur-
ing.early.development,.the.most.susceptible.window.falls.in.the.methylation.
state. of. the. genome,. which. in. general. leads. to. reprogramming. (Warnecke.
et. al.. 1998).. The. time. windows. include. (1). the. development. of. preimplan-
tation. embryo,. and. (2). the. development. of. germ. cells. closer. to. indifferent.
gonads.. Only. certain. genomic. regions. (i.e.,. imprinted. genes). are. protected.
from.demethylation.and.are.maintained.during.embryogenesis.(Bartolomei.
and.Tilghman.1997,.Olek.and.Walter.1997,.Sanford.et.al..1987,.Tremblay.et.al..
1997,. Warnecke. et. al.. 1998)..The. remethylation. of.the. germ. cells. appears.to.
be.dependent.on.the.germ.cells'.association.with.gonadal.somatic.cells.(i.e.,.
precursor.Sertoli.cells.and.tubular.myoid.cells)..Although.steroid.hormones.
are.not.produced.in.gonads.at.this.early.stage.of.development,.steroid.hor-
mone.receptors,.like.androgen.receptor,.ERα,.and/or.ERβ,.are.expressed.in.
Leydig.cells,.Sertoli.cells,.and.germ.cells.(Delbes.et.al..2006,.Greco.et.al..1992,.
Jefferson.et.al..2000,.Jirtle.and.Skinner.2007,.O'Donnell.et.al..2001,.Saunders.
et.al..1998,.2001,.van.Pelt.et.al..1999)..Therefore,.any.exogenous.factor.acting.
on.these.cells.at.the.time.of.reprogramming.of.the.genome.methylation.state.
inevitably.alters.the.epigenetic.modiication.of.the.germ.line..Consequently,.
transgenerational. transmission. of. an. altered. phenotype. or. genetic. trait.
appears.
ConclusionandFutureRecommendation
Environmental.pollutant.exposure.poses.a.potential.risk.for.human.health..
Epidemiological. and. laboratory. studies. have. demonstrated. adverse. effects.
of. such. exposure. on. animal. and. human. fertility. as. well. as. in. embryonic.
development..A.recent.study.has.indicated.that.pollutant.exposure.can.affect.
the.reproductive.health.of.future.generations.(Anway.et.al..2005)..It.will.be.
beneicial.to.establish.the.analytical.and.computational.techniques,.together.
with. the. in vitro . and. animal. models,. to. provide. an. analysis. platform. that.
can. reveal. the. “structure-activity”. relationship. of. common. and. emerging.
hazardous.chemical.pollutants.and.to.establish.risk.assessment.systems.to.
understand. the. mechanistic. actions. of. endocrine-disrupting. contaminants.
that. affect. human. reproductive. and. developmental. potentials.. It. has. been.
proposed. that. dioxins. and. pollutants. with. estrogenic-. or. antiestrogenic-
like.activities.can.have.the.most.striking.effect.on.reproductive.health..The.
newly. emerged. ED. contaminants. (i.e.,. bisphenol. A,. lame. retardants,. and.