Page 345 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

312 SECTION | II Organ Toxicity

VetBooks.ir cadmium and mercury, have been associated with pla- Multiple Congenital Contractures
cental toxicity, and this topic is covered in greater detail
Species of tobacco (Nicotiana spp.), poison hemlock
in Chapter 20 of this book.
(Conium maculatum) and lupines (Lupinus spp.) have all
been shown to be able to induce MCC or “crooked calf
disease” in cattle and, potentially, other species exposed
Selected Plant-Associated Teratogens
to their toxic principles at the appropriate stage of gesta-
and Abortifacients
tion. The condition is characterized by cleft palate and
Many potentially toxic plants have been found to induce limb and spinal contractures. Pyridine alkaloids (e.g.,
teratogenesis and/or abortion in mammals, including anabasine) in tobacco, piperidine alkaloids in poison
swainsonine-containing species of Astragalus and hemlock (e.g., coniine and γ-coniceine) and piperidine-
Oxytropis and plants associated with nitrate/nitrite intoxi- derived and quinolizidine alkaloids in lupines (e.g.,
cation. While it is not possible to extensively review all ammodendrine and anagyrine, respectively) cause stimu-
of these plants in this chapter, there are several well- lation then depression (depolarizing neuromuscular
documented examples of plant-induced birth defects and blockade) of nicotinic receptors in the fetus (Cheeke,
abortion which clearly illustrate the basic principles 1998; Burrows and Tyrl, 2001; Panter, 2002). This stimu-
regarding the pathogenesis of teratogenesis and abortion lation followed by neuromuscular blockade of fetal nico-
in domestic animals. There are a number of references tinic receptors during the critical period of palate and
which review the adverse effects of specific plants and/or joint development (i.e., gestational days 40 to 100 in cat-
toxicants on reproduction in some detail (Burrows and tle; days 30 to 60 in sheep; days 30 to 60 in swine)
Tyrl, 2001; Evans, 2011a; Panter and Stegelmeier, 2011; results in decreased fetal movement and the failure of the
Panter et al., 2017). palate and joints to form in a normal fashion (Panter,
2002; Panter and Stegelmeier, 2011).
Veratrum Californicum
Pine Needle Abortion
Jervanine alkaloids (e.g., cyclopamine, cycloposine and
jervine) in Veratrum californicum (false hellebore) and, Ingestion by cattle of pine needles (Pinus ponderosa)
potentially, some closely related plants have been associ- containing isocupressic acid (also possibly present in the
ated with the occurrence of cyclops lambs and other vegetation of some junipers and cypresses) results in late-
developmental abnormalities in sheep, as well as, less term abortion (Cheeke, 1998). Inhibition of the catechol
commonly, cattle and goats (Burrows and Tyrl, 2001; estrogen-induced blockade of potential-sensitive Ca21
Panter and Stegelmeier, 2011; Panter et al., 2017). The channels by isocupressic acid leads to enhanced entry of
mechanism of action of the teratogenic alkaloids in spe- divalent calcium into arterial smooth muscle cells supply-
cies of Veratrum involves interference with the sonic ing the gravid uterus and results in profound vasoconstric-
hedgehog (SHH) signal transduction pathway and the tion (Casteel, 1997; Cheeke, 1998; Burrows and Tyrl,
inhibition of neuroepithelial cell mitosis and migration 2001; Panter and Stegelmeier, 2011; Panter et al., 2017).
during neurulation and decreased proliferation of chon- This isocupressic acid-induced vasoconstriction can lead
drocytes (Cheeke, 1998; Burrows and Tyrl, 2001; Panter to at least a 50% reduction in the blood flow reaching the
and Stegelmeier, 2011). The specific developmental fetal circulation and causes fetal stress, leading to the
abnormalities and the precise timing of maternal exposure induction of premature parturition or abortion (Cheeke,
to Veratrum californicum, which results in these defects 1998; Burrows and Tyrl, 2001). Late-term abortion occurs
is as follows: cyclops lambs and prolonged gestation 2 14 days following heavy consumption of green or dry
(associated with the absence of pituitary gland) from pine needles and results in up to 75% of exposed cows
maternal exposure on days 12 to, particularly, day 14 of aborting or delivering dead or weak calves (Cheeke,
gestation; embryonic death from maternal exposure on 1998; Burrows and Tyrl, 2001; Casteel, 2007; Panter
gestational days 19 to 21; cleft palate from maternal and Stegelmeier, 2011). Dams are frequently dull and
exposure on gestational days 24 to 30, metacarpal and depressed, with weak uterine contractions, incomplete
metatarsal defects (limb reductions) and tracheal cartilage cervical dilation, retained placenta and frequent post-
defects (tracheal stenosis) from maternal exposure on ges- partum metritis (Cheeke, 1998).
tational days 28 to 31 and 31 to 33, respectively (Burrows
and Tyrl, 2001). No abnormal effects were observed with CONCLUDING REMARKS
maternal exposure to Veratrum californicum before day
10 or after day 35 of pregnancy, and Veratrum-associated Reproduction is a critical biological process, required for
birth defects can generally be prevented by avoiding financially viable livestock production, as well as species
exposure until at least 5 weeks after breeding. survival. Toxicant-induced abortions, congenital defects