Page 330 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Reproductive Toxicity and Endocrine Disruption Chapter | 17 297

VetBooks.ir EDCs can also hinder reproductive function in these spe- and/or continuing environmental exposures to EDCs
(Milnes et al., 2006).
cies (Evans, 2011a).

Endocrine Disruption in Wildlife Species
Endocrine Disruption in Humans
There have been many, well-documented instances of
Based, in part, on the observations of endocrine disruption
reproductive abnormalities in species of wildlife living in
in wildlife and ongoing concerns about reproductive dys-
environments contaminated by industrial and/ or agricul-
genesis, as well as the effects of embryonic and/or fetal
tural chemicals (McLachlan, 2001; Hess and Iguchi,
exposure to diethylstilbestrol (DES), the emphasis with
2002; Jobling and Tyler, 2006; McLachlan et al., 2006).
respect to endocrine disruption in humans and one of the
The deleterious reproductive effects of DDT on birds
bases for the “Theory of Hormone Disrupting Chemicals”
reported in Rachel Carson’s Silent Spring have been
(THDC) or the “Environmental Endocrine Hypothesis”
shown to be the result of eggshell thinning related to
(Krimsky, 2000, 2001) has been the enhanced effects of
abnormalities in prostaglandin synthesis induced by the
prenatal, as compared to postnatal, exposures to suspected
p,p-DDE metabolite of DDT (Lundholm, 1997; Guillette,
endocrine disruptors. The embryo and fetus, without a
2006). Wildlife populations are very likely sentinels for
developed blood brain barrier and with only rudimentary
endocrine disruption because of the contamination of the
DNA repair mechanisms and hepatic detoxifying and
aquatic habitats in which many of them live and the like-
metabolizing capabilities, are especially susceptible, as
lihood that predatory animals will have relatively high
compared to adults, to the adverse effects of low-level
exposures to chemicals which bioaccumulate within the
exposures to xenobiotics (Newbold et al., 2006). In addi-
environment (Hess and Iguchi, 2002). Lessons learned
tion, previous discussions in this chapter and other test-
from instances of endocrine disruption in wildlife species
books have described the important organizational events
can be applied to EDC exposures involving humans and
taking place during gonadal and phenotypic sexual differ-
domestic animals (Evans, 2017).
entiation, which are potentially very sensitive to altera-
tions in the normal endocrine milieu (Evans, 2017).
“Androgenic” and “Estrogenic” Effects Although still controversial, there is a growing body
of EDCs on Wildlife Species of evidence to support the observation that sperm counts
Prenatal and postnatal exposures to androgenic and estro- in men within some industrialized regions of the world
genic environmental contaminants, as well as chemicals have been decreasing over the last several decades (Swan
classified as having the opposite phenotypic effects, have et al., 2000; Skakkebæk et al., 2006; Jørgensen et al.,
been associated with various reproductive abnormalities 2006a). In conjunction with these alterations in sperm
in wildlife. Effluents from pulp and paper mills, as well numbers within ejaculates, there appears to have been a
as runoff from cattle feedlots where the synthetic andro- concurrent increase in developmental abnormalities
gen trenbolone was used for growth promotion, have within the male reproductive tract consistent with TDS
been shown to be androgenic and capable of masculiniz- (Skakkebæk et al., 2001). Similar to what has been
ing female fish (Orlando et al., 2004; Gray et al., 2006). observed in xenobiotic-exposed wildlife, reproductive
“Androgenization” or a state of indeterminate sexual dysgenesis in human males (i.e., TDS) is associated with
development encompassing both feminization and demas- a suite of clinical abnormalities which include reduced
culinization in males has been observed in populations of semen quality, cryptorchidism, hypospadias, decreased
fish, amphibians, reptiles, birds and mammals and is anogenital distance and testicular cancer (Skakkebæk
thought to be similar to the testicular dysgenesis syn- et al., 2001; Edwards et al., 2006). Failure of Sertoli cell
drome described in humans (Edwards et al., 2006). Adult proliferation and functional maturation within the seminif-
and immature amphibians exposed to the herbicide atra- erous tubules has been one mechanism proposed for the
zine, which has been associated with increased aromatase pathogenesis of TDS (Sharpe et al., 2003). The findings
activity in a number of species, have been reported to of a recently completely epidemiological study have sug-
exhibit various manifestations of feminization (Hayes gested a relationship between decreased anogenital dis-
et al., 2006). Hatchling, juvenile and adult male alligators tance and prenatal phthalate exposure in male infants
(Alligator mississippiensis), originating from a Florida (Swan et al., 2005), and a possible rodent model for
lake previously contaminated with DDT and other persis- human TDS has been developed using prenatal exposure
tent, bioaccumulated pesticides, as well as ethylene to dibutyl phthalate [di (n-butyl) phthalate] (Fisher et al.,
dibromide and DBCP, have demonstrated varying pat- 2003; Mahood et al., 2005, 2006).
terns of androgynization, including phallic malforma- In addition to phthalates, which are used as plastici-
tions, which are thought to result from ovo exposure of zers, a number of other widely used agricultural and
maternal origin, as well as post-embryonic modifications industrial chemicals have been associated with adverse