Reproductive Toxicology Flashcards
What are the 6 steps to the reproductive process?
- gametogenesis
- release of gametes
- formation of zygote
- embryonic fetal development during incubation or gestation
- birth/parturition
- lactation
What are the 2 general mechanisms of reproductive toxicity?
- alteration in endocrine function
- alteration in non-endocrine function, like gametogenesis
What are some general clinical signs of reproductive toxicosis?
- abortion
- dystocia
- retained placenta
- reduced fertility
- edema of prepuce and atrophy of testis
- enlargement of mammary glands in males
- vaginal discharge
- anestrous
- agalactia
- teratogenesis
What are the main 2 sources of zearalenone? What does it cause?
- mycotoxin produces by Fusarium graminearum commonly found in corn*, wheat, barley, oats, and forages (heat-stable and withstands pelleting)
- Zeranol (Ralgro), a growth-promoting implant for beef, cattle, and sheep
vulvavaginitis
What species are most susceptible to zearalenone toxicity? Why?
swine, especially pre-pubertal gilts
slower metabolism and enhanced enterohepatic recirculation
How is zearalenone metabolized? Excreted? What happens in the rumen?
in the liver to zeranol (α-zearalanol) and taleranol (β-zearalanol)
undergoes glucuronidation and sulfation and excreting mainly via bile and feces (enterohepatic recirculation!)
rumen microbes degrade about 30%
What swine are most sensitive to zearalenone toxicity? What species is least sensitive?
- prepubertal swine and cycling females
- females > young males > older males
poultry
How does zearalenone cause toxicity? What is its mechanism?
acts as an estrogen
binds to cytoplasmic receptor for estradiol-17β, whch causes translocation to the nucleus, and stimulation of estrogenism genes —> ovarian follicle matures and ovulation is inhibited due to reduced plasma FSH
(+ immunosuppression due to thymus atrophy and inhibition of macrophage activation)
What are the clinical signs of zearalenone toxicity in gilts and boards?
HYPERESTROGENISM:
- gilts: swelling and hyperemia of the vulva, mammary glands, and uterus, ovarian atrophy, vaginal discharge, vaginal and rectal prolapse
- boards: edema of prepuce, atophy of testis, reduced libido and sperm quality
What are the clinical signs of zearalenone toxicity in castrated/prepubertal male pigs and sows?
HYPERSTROGENISM:
- castrated/perpubertal males: enlargement of mammary glands, edema of prepuce, difficulty urinating
- sows: anestrous, nymphomania, pseudopregnancy, reduced litter size due to fetal resorption, weak or stillborn piglets
What are the clinical signs of zearalenone toxicity in sheep and heifers?
HYPERESTROGENISM:
- sheep: decreased ovulation rate and low lambing percentage
- heifers: enlargement of mammary glands, estrous behavior, turbid vaginal discharge
What clinical pathology is associated with zearalenone toxicity?
elevated serum progesterone and decreased prolactin and LH
How is zearalenone toxicity diagnosed?
- reproductive performance of herd/flock
- occurrence of reproductive problems while excluding other relevant causes of infertility
- PM reproductive lesions
- zearalenone analysis in feeds
- virgin prepubertal mice bioassay
What treatment is recommended for zearalenone toxicity? What is recommended for anestrous in sows?
- prompt discontinuation of suspect feed (reproductive functions should recover/regress in 1-4 weeks)
- treat vaginal or rectal prolapse and physical damage to external genitalia
- no adsorbent has been proven efficacious
PG2α - caused by retained corpora lutea
Where are broom/threadleaf snakeweed (Gutierrezia spp.) most commonly found? What species are most affected by toxicosis?
- BROOM = ubiquitous across North America
- THREADLEAF = southwestern US and northern Mexico in dry, desert habitats with sandy soil
sheep, cattle, goats
What causes variable toxicity of broomweed? What are the 3 toxic principles?
growing conditions, stage of growth, soil type (sandy > hard)
- monoterpenes/diterpenes
- saponins
- oxygenated flavonol methyl esters
What causes broomweed toxicosis? What reproductive signs are most common? What exacerbates these signs?
overgrazing forces animals to eat broomweed
- vulvar swelling and premature udder development
- abortion, retain placenta, stringy mucoid vaginal discharge
- stillbirth or premature birth or underweight calves
poor nutrition
What is seen in acute broomweed toxicosis? What clinical signs are observed?
non-reproductive signs
- anorexia, weakness
- mucopurulent nasal discharge, nasal pad crusting
- icterus, diarrhea, constipation
What treatment is recommended for cows with retained fetal membranes following broomweed toxicosis? How can toxicosis be prevented?
antibiotic therapy
- prevent grazing by ensuring adequate feed is available
- control broomweed with rangeland herbicides, like Tordon or Escort
What are the 3 most common plant sources of isocupressic acid?
- pines (Pinus ponderosa/contorta)
- junipers (Juniperus communis)
- cypress (Cupressus macrocarpa)
widely distributed in US and Canada
What is isocupressic acid? What does it commonly cause?
labdane diterpene found in green and dried needles, bark, and new growth tips of branches of pine trees
“pine needle abortion” - succinyl ICA and acetyl ICA also contribute to abortion after converted into ICA in the rumen
What species are most affected by isocupressic acid toxicity?
cattle and buffalos —> last trimester most sensitive
What is the mechanism of toxicity of isocupressic acid?
profound constriction of caruncular vascular bed decreases blood flow to fetus
- likely due to activation α2-adrenoreceptors that increase vascular tone and decreased uterine blood flow and delivery of nutrients and oxygen to the fetus = release of fetal cortisol and abortion/premature parturition
What are the most common clinical signs of isocupressic acid toxicity?
- last trimester* abortions typically in late fall, winter, and early spring
- premature udder development with milk production and vulvar swelling
- depression, dullness, udder and edema signal impending abortion
- premature birth of small and weak calves
- retained placenta* (removal = excessive bleeding, septic metritis)
- mucoid/hemorrhagic vaginal discharge
What actions have slight changes of success for treating retained placenta due to isocupressic acid toxicity? How can toxicity be prevented?
- uterine infusions
- prostaglandins
- oxytocin
- collagenases
avoid grazing pregnant cows around pine trees, especially in the third trimester
What plant contains quinolizidine alkaloids that have reproductive effects? What is the main clinical sign?
lupine
TERATOGENESIS due to anagyrine - arthrogryposis (crooked calf disease) resulting from reduced fetal movement due to neuromuscular blockade at critical stages in gestation
(WESTERN US)
What plant contains indolizidine alkaloids that have reproductive effects? What are the most common clinical signs?
locoweeds
- TERATOGENESIS - brachygnathia, contracture or overextension of joints, limb rotations
- infertility, abortions
- ovarian and testicular abnormalities
What plant contains piperidine alkaloids that have reproductive effects? What is the most common clinical sign?
poison hemlock
TERATOGENESIS due to γ-coniceine and coniine - neuromuscular blockade decreases intrauterine fetal movement = joint contractures, cleft palate, skeletal malformations
What reproductive effect does the tobacco plant have? How?
teratogenesis (arthrogryposis) especially in pigs
ababisine and anatabine caused decreased fetal movement
What reproductive signs are associated with ergotism and fescue? What is the mechanism of reproductive toxicity?
agalactia, abortion, dystocia, retained placenta, prolonged gestation, reduced conception and calving rates
- STIMULATION of D2 receptors = decreased prolactin = impaired lactogenesis and steroidgenesis due to low progesterone and high estradiol)
- STIMULATION of α1-adrenergic/serotonergic receptors and INHIBITION of D1 receptors = vasoconstriction with impaired circulation to placenta and abdominal/pelvic fat, uterine contraction causes abortion
- necrotic fat in abdominal and pelvic cavities obstructs genitourinary tract = dystocia
How does gossypol affect male and female reproductive tracts?
MALE = decreased spermatogenesis, spermatozoa abnormalities (aplastic midpiece)
FEMALE = decreased progesterone estradiol
How do selenium and onion affect the reproductive system?
SELENIUM = teratogenesis due to inhibition of DNA and RNA polymerases
ONION = abortion
How do nitrate/nitrite, moldy sweet clover, and red maple affect the reproductive system?
N/N = crosses placenta and induces fetal methemoglobinemia and hypoxia, abortion, stillbirth, infertility, reduced milk production
MOLDY SWEET CLOVER = dicoumarol crosses placenta, causing hemorrhage and fetal hypoxia = abortion in catle
RED MAPLE = abortion in mares
How do carbon monoxide and aflatoxins affect the reproductive system?
CO = crosses the placental barrier, causing fetal hypoxia (abortion)
AFLATOXINS = impair reproductive performance
