Page 338 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Reproductive Toxicity and Endocrine Disruption Chapter | 17 305

VetBooks.ir anticipated, that phytoestrogens, like other xenoestrogens, cussed with respect to their estrogenic and/or, in some
Some of the synthetic xenobiotics most commonly dis-
can function also as antiestrogens through the inhibition of
instances, their antiestrogenic activity include DES, DDT,
LH and FSH release from the anterior pituitary and by
competing with endogenous estrogens for receptor sites PCBs, bisphenol A, nonylphenol, kepone and TCDD
within the tubular genitalia (Cheeke, 1998; Evans, 2017). (MacLachlan, 2001). While the overall adverse effects of
xenoestrogens have already been discussed in this chapter
Zearalenone with respect to reproductive development and endocrine
disruption, there are several unique clinical aspects of
The estrogenic mycotoxin zearalenone is produced by
exposures to these types of xenobiotics which should be
Fusarium graminearum (formerly Fusarium roseum),
addressed for completeness. Prenatal human exposures to
under certain environmental and storage conditions and,
the synthetic, non-steroidal xenoestrogen DES have been
sometimes, in conjunction with vomitoxin or deoxyniva-
associated with feminization of the male fetus, as well the
lenol (DON). Cereal grains associated with zearalenone
increased occurrence of clear cell adenocarcinoma of the
production include corn, wheat, barley and oats, and some
vagina in young women (McLachlan 2001; McLachlan
grasses in New Zealand have also been reported to have
et al., 2006; Newbold et al., 2006; Rogers and Kavlock,
been contaminated with zearalenone (Cheeke, 1998).
2008). The use of DES for mismating or pregnancy pre-
Swine have been shown to be particularly susceptible to
vention in dogs has been, in some instances, associated
the adverse effects of zearalenone, with pre-pubertal gilts
with an increased incidence of cystic endometrial hyper-
being affected by concentrations of zearalenone in the
plasia and pyometra. The apparent ability of the widely
feed as low as 1 to 3 ppm (Cheeke, 1998; Casteel, 2007).
distributed xenoestrogen bisphenol A to cause adverse
The increased sensitivity of pigs to the estrogenic effects
developmental effects at very low environmental concen-
of zearalenone is most likely related to the slow metabo-
trations and in a manner characterized by a non-
lism and enhanced enterohepatic recirculation of zearale-
monotonic (inverted U- or U-shaped) dose response
none noted in this particular species (Cheeke, 1998).
has been difficult for some researchers to reproduce and
Cattle and other ruminants can be affected by zearalenone
remains controversial (Welshons et al., 2006). However,
but only at dietary concentrations much higher than those
this particular issue is worthy of further, detailed discus-
associated with clinical signs in swine (Casteel, 2007).
sions regarding appropriate reproductive endpoints and
Hyperestrogenism in pre-pubertal gilts is characterized by
necessary experimental controls, given the topic’s scien-
swelling of the vulva and mammary glands, uterine
tific ramifications, societal relevance and potential appli-
enlargement and ovarian atrophy, and testicular atrophy
cations to other EDCs (Evans, 2017).
and preputial swelling have been observed in immature
male swine (Cheeke, 1998). As with other xenoestrogens,
Xenoandrogens
interference with estrogenic feedback mechanisms and
various ovarian abnormalities, including follicular cysts, While the emphasis in the area of endocrine disruption has
have been observed with excessive exposure to zearale- traditionally been on the adverse effects of xenoestrogen
none. Since estrogens are luteotrophic in swine, zearale- reproductive development and function, there is increasing
none can be associated with prolonged luteal phases evidence that there are also instances of endocrine disrup-
(pseudopregnancy), as well as nymphomania in cycling tors having androgenic activity. The effluents from pulp
gilts and sows, depending on the phase of the estrous and paper mills have recently been shown to be able to
cycle at the time of exposure. masculinize female fish (Gray et al., 2006). In addition,
the runoff from cattle feedlots, where the synthetic andro-
Synthetic Xenoestrogens and Antiestrogens gen trenbolone was used for the promotion of growth, has
also been shown to have androgenic activity and is also
A wide range of agricultural and industrial chemicals, as
suspected of being associated with masculinization of
well as pharmaceuticals used in birth control preparations,
females in wildlife species (Orlando et al., 2004).
have estrogenic and/or antiestrogenic activities, depending
on the endocrine environment, presence of endogenous
estrogens and stage of development at the time of expo- Teratogenesis and Abortion
sure. The type of tissue and physiological response being
discussed, as well as the relative distribution of ERα and Mechanisms of Actions of Teratogenesis
ERβ receptors, will also affect the types of endocrine and Abortion
effects observed in a given circumstance. As has been A large number of xenobiotics have been classified with
emphasized previously, the developing fetus is particularly respect to their teratogenic potential, and these are listed
susceptible to the adverse effects of estrogenic and anties- in Table 17.2. The ability of EDCs to interfere with phe-
trogenic endocrine disruptors (Hess and Iguchi, 2002). notypic sexual differentiation in the fetus has already