15. Toxicity: Reproductive System

will refer to any manifestations of xenobiotic exposure reflecting adverse effects on the physiological processes and associated behaviors and or anatomical structures involved in animal reproduction or development

reproductive toxicity

refers to any adverse effect on the developing organism associated with either pre-conception parental exposures to toxicants or post-conception xenobiotic exposures to the embryo, fetus, or pre-pubertal offspring

developmental toxicity

refers specifically to developmental defects induced by toxicant exposures occurring between conception and birth

teratogenesis

In general, what are the main mechanisms in which toxicants affect the reproductive system?

T
A
E

• toxicant-induced cellular dysregulation

• alterations in cellular maintenance

• endocrine disruption

effects which are mediated directly by interactions between the xenobiotic and an endogenous hormone receptor, as well as those adverse effects which alter hormonal functions without direct interactions between toxicant and an endogenous receptor

endocrine disruptor

What phytoestrogen is contained in species of clover, including subterranean clover, red clover, white clover, and alsike clover?

phytoestrogens classified as isoflavones

What are the parent glycosides for the most clinically relevant isoflavones in clover?

formononetin, biochanin A, and genestein

What is the primary phytoestrogen in alfalfa?

coumestrol

True or false: Coumestrol has significantly greater estrogenic activity than many of the isoflavones present in other legumes, and this activity generally decreases during the drying process involved in hay production.

true

What has been reported in several instances of phytoestrogen exposure and can be especially evident in dairy breeds of cattle and goats?

precocious mammary development

disease in sheep, and to a lesser extent, cattle is associated with the consumption of the isoflavones in clover, resulting in infertility associated with abnormal estrous cycles and structural and functional changes in the cervix

clover disease

True or false: Phytoestrogen-induced alterations in ovine cervical mucus interfere with the slow, sustained transport of motile spermatozoa from their cervical reservoirs.

true

What is the affect of genestein on exposed gilts?

can induce structural changes, and possibly, irreversible organizational abnormalities in the cervix and uterus

What is the effect of coumestan in cattle?

various and sometimes seemingly conflicting clinical presentations (hyperestrogenism, nymphomania, swelling of the external genitalia, estrus suppression, inhibitions of ovulation and cystic ovarian disease)

What is the effect of slaframine in dairy cattle?

causes marked drop in milk production

What is the toxic principle in locoweed (oxytropis spp and astragalus spp)?

swainsonine

What is the major problem encountered with locoweed poisoning?

decreased fertility in cattle characterized by decreased conception rates and lower calving percentages

What estrogenic mycotoxin does fusarium graminearum produced? It can sometimes be produced in conjunction with what?

zearalenone; vomitoxin or deoxynivalenol (DON)

What cereal grains are associated with zearalenone production?

corn, wheat, barley, and oats

What species have been shown to be particularly susceptible to the adverse effects of zearalenone?

swine

What is the increased sensitivity of pigs to the estrogenic effects of zearalenone most likely related to?

the slow metabolism and enhanced enterohepatic recirculation of zearalenone

How is hyperestrogenism in pre-pubertal gilts characterized?

swelling of the vulva and mammary glands, uterine enlargement, and ovarian atrophy

What endophyte is associated with tall fescue grass?

neotyphodium coenophialum

What toxin is involved with that endophyte?

ergovaline

What is the effect of fescue toxicosis in horses?

blocks signals of parturition causing no udder development and the foals keep growing

What is the effect of fescue toxicosis in cattle?

epidemic hyperthermia (summer syndrome)

When does most fescue toxicosis damage occur? Therefore, what should be done?

in the last 3 months of gestation; put on dry lot or stall for 3 months

What can be used to treat fescue toxicosis? What does it do? What is a downside to this?

domperidone; promotes mammary development; may result in early leakage and loss of colostrum

While ergot toxicity can occur on any seed head, what is it commonly seen on?

rye

yellow, polyphenolic pigment, which is contained in most of the parts of plants belonging to the gossypium genus and is concentrated in pigment glands within the seeds

gossypol

What is generally observed in mono-gastric animals with gossypol toxicity?

hepatic, renal, cardiovascular, and pulmonary abnormalities

What happens to peri-pubertal or sexually mature males when exposed to sufficient dosages of free gossypol?

adversely affects the seminiferous epithelium and disrupts normal spermiogenesis

What is the toxic agent in pine?

isocupressic acid

What is the effect of ingestion by cattle of pine needles?

late-term abortion with retained placenta

True or false: When pine is consumed, there is inhibition of the catechol estrogen-induced blockade of potential sensitive Ca channels by isocupressic acid that leads to enhanced entry of divalent calcium into arterial smooth muscle cells supplying the gravid uterus and results in profound vasoconstriction.

true

What are the toxic agents found in veratrum californicum?

cyclopamine, cycloposine, and jervine

Cyclopamine, cycloposine, and jervine have been associated with what?

the occurrence of cyclops lambs and other development abnormalities in sheep, as well as, less commonly, cattle and goats

What is the mechanism of toxicity that cyclopamine, cycloposine, and jervine have?

involves interference with the sonic hedgehog (SHH) signal transduction pathway and the inhibition of neuroepithelial cell mitosis

What have species of tobacco, poison hemlock, and lupines all been shown to be able to induce? What are they characterized by?

MCC or crooked calf disease in cattle and potentially other species; cleft palate and limb and spinal contractures