Page 335 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

302 SECTION | II Organ Toxicity

VetBooks.ir TABLE 17.1 (Continued) Observed Effect(s) on Male

Xenobiotic
Ethylene glycol Decreased sperm number and motility
Environmental factors
Heat Damaged sperm chromatin and quality
Microwaves Decreased sperm number
Radiation High doses: death of stem cells and permanent azoospermia
Stray voltage (AC and DC) Decreased sperm number
Physiological factors
Stress Decreased sperm motility
Fever (hyperthermia) Damaged sperm chromatin and quality
This table was adapted, with permission, from Ellington and Wilker (2006).

Like lead, cadmium is thought to adversely affect cottonseed meal being much more readily bioavailable
male reproduction by several different mechanisms. With than the gossypol contained in whole seeds (Cheeke,
respect to spermatogenesis, the stage of the seminiferous 1998; Casteel, 2007).
epithelium associated with spermiation appears to be Gossypol can cause systemic and reproductive disease
specifically inhibited by cadmium (Thomas, 1995). syndromes, depending on the species of exposed animal
Cadmium has also been shown to have possible interac- and the dosage of free gossypol consumed (Randel et al.,
tions with the hypothalamic pituitary gonadal axis 1992). The toxic effects of gossypol are cumulative, and
(Akinloye et al., 2006). The endothelium of the testicular systemic disease, characterized by hepatic, renal, cardio-
and epididymal vasculature is extremely susceptible to vascular and pulmonary abnormalities, is generally
toxic insult by cadmium, potentially resulting in reduced observed in monogastric animals (Cheeke, 1998). Mature
vascular perfusion and testicular necrosis (Haschek et al., ruminants are considered to be relatively resistant to the
2010). Cadmium can also alter the actin filaments in the severe systemic effects of free gossypol because of the
junctional complexes between adjacent Sertoli cells, propensity of this form of the pigment to become bound
thereby disrupting the integrity of the blood testis bar- to proteins in ruminal fluid and, therefore, “detoxified”
rier (Thomas and Thomas, 2001). Cadmium can interfere (Casteel, 2007). Gossypol-induced male subfertility has
with the cellular metabolism of zinc, an essential trace been observed in monogastrics and, especially, ruminant
element necessary for normal reproductive function, and species and is dependent on the dosage of free gossypol
diets deficient in zinc can predispose individuals to the and the duration of gossypol exposure (Randel et al.,
toxic effects of cadmium (Akinloye et al., 2006). 1992; Cheeke, 1998).
Pre-treatment with zinc has been reported to reduce the Exposure of peri-pubertal or sexually mature males to
incidence of cadmium-induced Leydig cell cytotoxicity sufficient dosages of free gossypol adversely affects the
and neoplasia (Thomas, 1995). seminiferous epithelium and disrupts normal spermiogene-
sis, resulting in spermatozoa with aplastic midpieces (i.e.,
segmental aplasia of the mitochondrial sheath) (Randel
Gossypol et al., 1992; Chenoweth et al., 2000). Additional sperm
Gossypol is a yellow, polyphenolic pigment, which is abnormalities, possibly associated with gossypol-induced
contained in most of the parts of plants belonging to the oxidative damage (Velasquez-Pereira et al., 1998), can
Gossypium genus and is concentrated in pigment glands potentially develop as stressors related to the acquisition
within the seeds (Morgan, 2004; Casteel, 2007). Gossypol of motility in the epididymidis, and alter the structural
exists as two isomers (enantiomers) within plants (1 and integrity of already weakened spermatozoa (Chenoweth
the more toxic 2), and these isomeric forms can be non- et al., 2000). The spermatozoal abnormalities induced by
toxic and bound to plant proteins or toxic and “free” or exposure of immature bulls to free gossypol are most
unbound (Cheeke, 1998). The concentrations of the toxic likely reversible (Hassan et al., 2004) and can be amelio-
free form of gossypol vary widely in whole seeds and rated by concurrent treatment with vitamin E (Velasquez-
meals, with the gossypol in direct solvent-extracted Pereira et al., 1998). Total dietary concentrations of free