teratogenicity and reproductive toxicity

By what mechanism does locoweed ( oxytropis, astragalus) cause abortion, infertility and congenital defects?

1. swainsonide alkaloids

2. enzyme inhibition- lysosomal a-mannosidase and golgi mannosidase II

3. sugar accumulation-

4. lysosomal swelling

5. cell dysfunction- neurons and other vital tissus

what are CS/ pathology of locoweed toxicity?

fluid accumulation in the placenta, affects cotyledonary development → fetal death then abortion

vasoconstriction/ vascular resistance in fetus → interrupts blood flow → fetal death, abortion

when are cows most at risk for pine needle toxicity?

last trimester

how does pine needle tree cause abortions?

isocupressic acid reduces blood flow to the uterus and placenta

consumption of 3-5 lbs of pine needles for several days could trigger an abortion

what plants can cause crooked calf disease?

poison hemlock, Lupinus, Nicotiana

how does poison hemlock cause severe birth defects?

piperidine alkaloids, ingested bt days 40-1— cause severe birth defects in developing fetuses.

what is the general mechanism behind crooked calf disease?

alkaloid induced inhibition of fetal movement during specific gestational periods

characterized by skeletal contracture- type malformations and occasional cleft palates

what are the main consequences of veratrum sp?

craniofacial malformations, cyclopia, embryonic loss in sheep and goats

what is the mechanism of veratrum sp?

steroidal alkaloids- cyclopamine and jervine → activate sodium ion channels → rapid cardiac failure / stimulation of vagal nerve

cyclopamine inhibits Shh pathways which is critical for fetal development → defects in CNS → cyclopia and jaw deformities

what plants are considered veratrum sp.?

Corn lily, flase hellebore, skunk cabbage

what plants can cause nitrate poisoning?

sorghum, pearl millet, sudan grass

what is the mechanism of nitrate poisoning?

overfertilized/ drought stress forage

nitrate → nitrite→ formation of methemoglobin → no oxygen carrying capacity → crosses the placenta → interrepts oxygen supply to fetus → abortion

what are the main effects of nitrate poisoning?

fetal hypoxia, abortions, reduced fertility

what is the treatment for nitrate poisoning?

methylene blue

what are signs of nitrate poisoning?

abrupt onset- labored respiration, trembling, weakness, staggering gait, sometimes blindness

fall to ground with mouth open, bluish discoloration of tongue and cornea → fatal

what pathological lesions can be seen with nitrate poisoning?

tissues/ blood appear dark colored ; petechial hemorrhages

what trimester of pregnancy is most affected by teratogens ?

first

what is the main reproductive effects of organochloride pesticides?

endocrine disruption; decreased fertility

what is the main reproductive effects of organophosphate/ carbamates ?

impaired spermatogenesis; embryotoxicity

what is the main reproductive effects of polychlorinated biphenyls?

reduced fertility; fetal loss; endocrine disruption

what is the main reproductive effects of dioxins ?

teratogenicity; fetal mortality

what is the main reproductive effects of polycyclic aromatic hydrocarbons?

impaired gametogenesis; embryotoxicity

what is the mechanism of heavy metals that cause reproductive toxicity?

generation of free radicals, reaction oxygen/ nitrogen species → reduction in antioxidant stores → decrease in detoxification of ROS → oxidative stress → disruption of cellular hemostasis

CNS disorders, liver and kidney problems, reproductive failure, endocrine abnormalities, depression and vision disturbances

what are the effects of heavy metal toxicity on male reproductive system?

neg effects metallothionein mRNA for protecting spermatogenesis

oxidative damage → impacts sperm maturation

cadmium limits motility

blood testicular barrier disruption → sperm abnormalities

inhibits androgen production

dec in testosterone production

what are the effects of heavy metal toxicity on female reproductive system?

DNA damage→ ROS → oocyte death during division

toxic metals damage ovarian granulosa cells → dec steroidogenesis

crosses the placental barrier to reach the fetus → developmental problems

what are the consequences of heavy metal toxicity on a pregnant animal?

spontaneous abortion, endometrial cancer, estrogen - dependent diseases of mammary glands

what are the consequences of arsenic poisoning on male reproduction?

semen and sperm quality decreases, testicular toxicity, sperm apoptosis, sex hormone disruption

what are the consequences of arsenic poisoning on female reproduction?

spontaneous miscarriage, sex hormone disruption, reproductive cycle disruption, impair fecundity

what are the effects of lead on reproductive function?

CNS, GIT, hemopoietic system, and neuro signs (bellowing, blindness, dullness, head pressing, opisthotonosis, convulsions and coma)

leads to disorders in prostatic function, including prostate hyperplasia and cancer, as well as a reduction in sperm motility

what are the effects of cadmium on reproductive function?

causes nephropathy, anemia, bone demineralization, congenital defects, stillbirths, and abortion

subclinically: immunotoxicity, oxidative stress, reduced reproductive performance, endocrine disruption, altered micronutrient profiles, and poor weight gain

what plants can help prevent heavy metal toxicity if allowed to grow before livestock graze?

sunflower, indian mustard, vetiver grass, or willow

what are the general mechanisms of mycotoxin- mediated reproductive toxicity/ teratogenicity?

DNA damage, inhibition of protein synthesis, oxidative stress and cell death, hormonal disruption, impaired placental nutrient transfer

what alfatoxin is most significant and potent?

AFB1

what are the effects of AFB1 in male reproductive function?

impairs spermatogenesis, reduces sperm production, and lowers serum testosterone by disrupting steroidogenesis

what are the effects of AFB1 in female reproductive function?

disrupts oocyte maturation, arrests follicular development, and damages granulosa and ovarian somatic cells

fetal: microphthalmia, fetal growth retardation, and skeletal defects

what species exhibits the strongest response to alfatoxins?

poultry

what are the systemic effects of AFB1?

liver- injury, steatosis, fibrosis of the live

gut barrier dysfunction, microbiota dysbiosis, gut- liver axis

reproductive toxicity

stunted growth

what is the mechanism of fumonisin (B1)?

competitively inhibits sphingolipid biosynthesis and disrupts folate metabolism → neural tube defects, growth retardation, and developmental abnormalities → fetal mortality

what is the mechanism of fumonisin (B1) in swine?

crosses the placental barrier → disruption in maternal and fetal sphingolipid metabolism → increases incidence of embryonic resorptions, causing growth retardation and incomplete orgonogenesis

what are the main reproductive effects of zearaleonone?

potent estrogenic mycotoxin→ causes hyperestrogenism, pseudopregnancy, vulvar edema, reduced sperm motility, and impaired folliculogenesis in swine, cattle, and equids

congenital malformations → skeletal malformations in carpal and tarsal bones of neonates, derma cysts

what are CS of trichothecenes in poultry?

lesions at the edges of the beaks, abnormal feathering, reduced egg production, eggs with thin shells, reduced bodyweight gain, poor hatchability and mortality

what is the mechanism of trichothecenes?

disrupts reproductive endocrine exes, inhibits hormone synthesis, suppresses gametogenesis, and triggers skeletal or morphological malformations in developing fetuses

what are CS of fescue toxicosis (endophyte toxicity)?

progressive lameness, anorexia, hyperthermia, rough hair coat, depression, and later dry gangrene of the distal limb, reduced milk yield, and reduced conception rates

ergotism is highly toxic to

gravid mares

what are CS of ergotism in mares?

prolonged gestation length, abortion, dystocia, agalactia, foal and mare mortality, tough and thickened placentas, weak foals

what are preventative measures for mycotoxin toxicity?

proper storage of grains and feed, monitor feed for fungal contamination, use mycotoxin binders where appropriate, remove moldy feed , routine feed quality testing

what is the main reproductive effect of albendazole?

teratogenic during ealy gestation

what is the main reproductive effect of grisofulvine?

teratogen

what is the main reproductive effect of ketoconazole?

suppresses testosterone synthesis, infertility

what is the main reproductive effect of steroids?

fetal malformations and abortion risk

what is the main reproductive effect of cyclophosphamide?

severe embryotoxicity and teratogenicity

what is the main reproductive effect of excess vitamin A?

congenital malformations

what is the main reproductive effect of tetracyclines?

skeletal and dental abnormalities

What fungus causes endophyte toxicity?

Epichloe (neotyphodium) coenophiala

What fungus is responsible for ergotism in mares?

Claviceps

What food stuff does claviceps commonly infect?

Rye, wheat, oats