Page 331 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

298 SECTION | II Organ Toxicity

VetBooks.ir reproductive effects in humans and/or rodent models. In and, potentially, even death (Casteel and Evans, 2004).
Multiple congenital contractures (MCC) (“crooked calf
epidemiological studies a correlation has been shown
disease”) associated with the ingestion of lupines
between reduced semen quality in men within certain
regions of the United States and the metabolites of several (Lupinus spp.) have resulted in the loss of large numbers
economically important herbicides (Swan et al., 2003a, b). of calves in the western United States (Panter, 2002), and
Metabolites of the commercially available fungicide vin- multiple species of livestock exposed to swainsonine-
clozolin have been demonstrated to interfere with interac- containing plants (e.g., species of Astragalus and
tions between androgens and their nuclear receptor, Oxytropis in North America species of Swainsona in
resulting in antiandrogenic effects on exposed rodents Australia) have experienced congenital defects, abortions
(Wong et al., 1995; Monosson et al., 1999; O’Connor and/or ovarian and testicular abnormalities (Cheeke,
et al., 2002; Kubota et al., 2003; Gray et al., 2006). It has 1998). Cleft palate, cyclops lambs, prolonged gestation
been reported that, at concentrations well below those and various tracheal and limb deformities have resulted
routinely found in humans, bisphenol A, which is widely from different periods of exposure of pregnant ewes to
used in the plastics industry and other manufacturing pro- Veratrum californicum (false hellebore) (Burrows and
cesses, can initiate nongenomic estrogenic responses with Tyrl, 2001). Ergot alkaloids produced by the tall fescue
plasma membrane receptors and interact with the nuclear endophyte Neotyphodium coenophialum are responsible
estrogen receptor as a SERM (Welshons et al., 2006). It for suboptimal reproductive performance in large numbers
has also recently been reported that, as might be expected, of cattle and horses, with late-gestational mares being par-
more bisphenol A is absorbed if included in the diet simi- ticularly susceptible to endophyte-related prolonged gesta-
lar to what would be observed in actual environmental tion and agalactia (Evans et al., 2004; see Chapter 72 of
exposures, as opposed to administered as an oral bolus, this book).
which is normally what occurs in an experimental setting
(Sieli et al., 2011). Concerns have also been raised about
the antiandrogenic activity of pyrethroid insecticides Endocrine Disruption in Domestic Animals
(Zhang et al., 2008), which are commonly used without With respect to the adverse reproductive effects of
the awareness that these compounds have the potential to endocrine disruption on domestic animals, there have
affect reproductive function at levels of exposures less been many instances of impaired reproductive function
than those associated with neurotoxicity. With the involving naturally occurring EDCs of plant and fungal
increased societal awareness of the possible effects of origin. However, there is still much to be learned about
hormonally active xenobiotics on human reproduction, the potential adverse effects of pre- as well as postnatal
further research is required to make educated decisions, environmental exposures to EDCs in these species
based on “good science,” with respect to label instructions where selection of breeding animals is often based on
and precautions for continued use and/or regulation of reproductive soundness. Postnatal exposures to phytoes-
economically important chemicals associated with the trogens in some leguminous plants, including soybeans,
potential for reproductive abnormalities in humans and/or have resulted in reproductive abnormalities and subferti-
documented impairment of reproductive function in labo- lity in multiple species (Cheeke, 1998; Ford et al.,
ratory animals. 2006). The adverse effects of postnatal exposures to the
estrogenic mycotoxin zearalenone on swine fertility
The Effects of Reproductive Toxicants have also been well documented (Cheeke, 1998). Many
of the reproductive effects of the common forage-
on Domestic Animals
related disease syndrome referred to as “fescue toxico-
Abortion, Teratogenesis and Impaired Fertility sis” clearly involve the endocrine disruptive effects of
in Domestic Animals ergot alkaloids on prolactin secretion. In experimental
Animal-based agriculture is dependent on the efficient studies, female swine appear to be more sensitive than
production of viable and reproductively functional off- rodents to the effects of the synthetic herbicide atrazine
spring. Toxicant-induced abortions, congenital defects on the hypothalamic pituitary gonadal axis (Gojmerac
and male or female infertility can have devastating effects et al., 2004), and it is possible that companion and agri-
on livestock production. Cattle are commonly at increased cultural animals are also more susceptible than labora-
risk, especially under drought conditions, for adult mortal- tory species to other EDCs. As many hormonally active
ity and abortions in pregnant cows related to the con- xenobiotics also have important agricultural and indus-
sumption of nitrate-accumulating forages (e.g., Sorghum trial uses, it is important to continue research which
spp., oat hay (Avena sativa), cornstalks (Zea mays), and attempts to accurately predict the effects of environmen-
many others), which cause nitrite-induced fetal meth- tal exposures to EDCs, as well as other reproductive
emoglobinemia, hypoxia and, consequently, fetal stress toxicants, on domestic animals.