Environmental Engineering Reference
In-Depth Information
2005,.Ohtake.et.al..2003,.2007,.Puga.et.al..2000,.Vogel.et.al..2007,.Wormke.et.al..
2003)..Due.to.the.unavailability.of.the.AhR.x-ray.crystal.structure,.quantita-
tive. structure-activity. relationship. (QSAR). models. have. been. used. for. the.
binding.prediction.for.virtual.screening..Comparative.molecular.ield.anal-
ysis. (CoMFA),. VolSurf,. and. Hologram. QSAR. (HQSAR). models. have. been.
constructed. using. a. training. set. of. 84. AhR. ligands. (Aravindakshan. et. al..
2004,.Lo.et.al..2006,.Tuppurainen.and.Ruuskanen.2000)..The.results.showed.
that.CoMFA,.VolSurf,.HQSAR,.and.the.hybrid.models.give.good.correlation..
Since. the. techniques. analyzed. show. a. good. prediction. quality. against. an.
external.test.set,.particularly.the.HQSAR.and.the.hybrid.model,.these.mod-
els.were.concluded.to.be.able.to.predict.AhR.binding.in.virtual.screening.
Compared. to. dioxin/AhR-mediated. actions,. contaminants. that. cause.
estrogenic. and/or. antiestrogenic. activities. were. shown. to. have. striking.
effect. on. animals,. demonstrating. the. power. of. estrogen. in. environmental.
signaling.(McLachlan.2001)..It.is.particularly.true.when.we.look.at.various.
domains.in.an.evolutionary.perspective;.the.DNA-binding.domain.and.the.
ligand-binding. domain. of. estrogen. receptor-α. (ERα). are. conserved. across.
metazoans. (McLachlan. 1993,. Thornton. et. al.. 2003).. Global. environmental.
contaminants,.POPs.(i.e.,.dichlorodiphenyl-trichloroethane.[DDT],.hydroxyl-
ated.PCBs,.bis-phenol.A,.
p
-nonylphenol,.and.dioxins),.and.heavy.metals.(i.e.,.
cadmium.and.mercury).can.exhibit.either.or.both.estrogenic.and.androgenic.
activities. (Johnson. et. al.. 2003,. Martin. et. al.. 2003,. McLachlan. 2001).. Some.
newly. identiied. emerging. contaminants,. like. perluorinated. compounds.
(PFOA).and.lame.retardants,.were.also.reported.to.possess.estrogenic.activi-
ties. (Maras. et. al.. 2006,. Meerts. et. al.. 2001).. More. importantly,. nongenomic.
rapid.xenoestrogen.actions.were.demonstrated.when.the.xenoestrogens.bind.
to.a.common.membrane.binding.site.that.has.the.pharmacological.proile.of.
the.γ-adrenergic.receptor.(Nadal.et.al..2000).
EndocrineDisruptorsandTheirEffectsonAnimalFertility
Mammalian. spermatogenesis. and. folliculogenesis. are. characterized. by.
a. complicated. cascade. of. processes. that. occur. due. to. the. inluence. of. the.
hypothalamus-pituitary-gonadal.axis.as.well.as.the.
de novo
.auto/paracrine.
circuit..The.fundamental.role.of.the.hormones.involved.is.to.enable.a.coor-
dinated.regulation.of.the.processes.that.allow.for.the.development.of.highly.
differentiated. spermatozoa. and. the. selection. of. the. itness. oocyte. for. ovu-
lation.. Any. interruption. of. the. hormonally. mediated. regulation,. the. con-
stituents.of.the.microenvironments.in.seminiferous.tubules,.and.developing.
follicles. may. result. in. a. transient/long-term. modiication. of. the. hormonal.
feedback. circuitry,. disturbance. of. gametogenesis,. and. possibly.the.epigen-
etic.modiication.of.the.gametes/germ.cells.
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