Teratogenicity and Reproductive Toxicity

Plant sources

locoweeds( Astragalus sp./ oxytropis sp.)

pine needle

poison hemlock

Lupinus/Nicotiana sp.

Veratrum sp.

Plants with high nitrate content

plants with phytoestrogens

Locoweeds- Astragalus sp.

Locoweeds- Oxytropis sp.

Locoweeds

contains swainsonine alkaloids which cause lysosomal storage disease

inhibit lysosomal alpha-mannosidase and golgi mannosidase II

cells cannot break down mannose-rich sugars causing them to build up inside lysosomes

swollen lysosomes disrupt normal cell work, especially in neurons and other vital tissues

fluid accumulation in the placenta affects cotyledonary development→ fetal death followed by abortion

Pine needle (pinus ponderosa)

coniferous tree: needles contain isocupressic acid which reduces blood flow to the uterus and placenta

cows are most at risk during the last trimester (final 30 to 60 days of pregnancy)

both green or dried needles from pondersa pine trees can be harmful for pregnant cows

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

crooked calf disease (teratogenicity)

poison hemlock -conium maculatum

lupinus sp

nicotiana sp

caused by maternal ingestion of toxins: differences → susceptible gestation periods, severity between livestock species

alkaloid induced inhibition of fetal movement during specific gestational periods

characterized and occasional cleft palates in cattle and goats

susceptible periods are 30-50 days for cleft palate and 50-100 days for multiple congenital contractures

poison hemlock

contains piperdine alkaloids when preganant cows graze sub lethal amounts of poison hemlock between days 40 and 100 of gestation these alkaloids cause severe birth defects (crooked calf disease)

Veratrum sp. (corn lily, false hellebore, skunk cabbage)

contains steroidal alkaloids, cyclopamine and jervine

activate sodium ion channels- rapid cardiac failure and a fatal condition

stimulation of vagal nerve

teratogenic- cyclopia, cleft palate, anophthalmia, metacarpal hypoplasia

small ruminants/grazing livestock

cyclopamine inhibits the sonic hedgehog signaling pathway which is critical for embryonic patterning and brain/facial development

leads to defects in the central nervous system and skull notably cyclopia and jaw deformities

human toxicity: mistaken for wild leek/ramps (GI and cardiogenic effects of veratrum alkaloids: nausea, vomiting hypotension, an bradycardia

ramps vs false hellebore: smell, leaf texture/shape, growth/location, growth pattern, toxicity

Nitrate poisoning (pearl millet, sorghum, sudan grass)

signs: abrupt onset; noticed within hrs after eating hay and cause the fatal condition, weak labored respiration, trembling of muscles, weakness, staggering gait and sometimes apparent blindness, animal may sink to the ground fall on its side and lie with its mouth open, bluish discoloration of the tongue and cornea of the eyes → fatal condition , pregnant animals may abort later

pathology: tissue/ blood appear dark colored; petechial hemorrhages; forage/silo samples should be taken from multiple spots sent in airtight containers, time between sampling and delivery to lab should be short as possible

treatment: Methylene blue (1-2%) 4-15mg/kg BW, IV

prevention: adapt animals using oral prebiotics (before administration of forages), reduce the level of nitrite production in ruminants→ management tool assist cattle producers during the feeding of drought stressed high nitrate forages

Reproductive toxicity caused by chemical

first trimester (organogenesis period) when teratogens most easily trigger major malformation, reproductive toxicants can interfere with gamete formation, fertility rate, preganacy, fetal development, or offspring survival, exposure may occur through contaminated food, water, soil, air, or industrial/agricultural environments

Endocrine disruptors

Endocrine-disrupting chemicals are environmental chemicals that affect the hormonal function in the body

EDCs have been linked to reproductive tract abnormalities, infertility, cardiovascular disease, asthma, autoimmune disease, and neurocognitive disorders

sources of heavy metal contamination

industrial effluents, automobile emissions, waste water from industries (chromium), grazing the polluted pastures along roadsides/mining areas, fertilizers phosphate and organic (sewage sludge and animal manure)

Arsenic

sources: contaminated pastures, dipping, spraying chemicals, pesticides, herbicides, feed additives, ground water

As accumulates in liver → distributes to kidneys, spleen, lungs

induces GI, nervous, cardiovascular symptoms

Lead

higher frequency of poisoning

sources: contaminated feed/water, burning of fossil fuels, paint industries, combustion of coal

Pb can cross placental barrier→ affects the fetus of exposed animal

CNS, GI, hemopoietic system, and neurological signs (bellowing, blindness, dullness, head pressing, opisthotonos, convulsions and coma)

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

Cadmium

Mycotoxins

secondary metabolites produced by fungi which contaminate a wide variety of agricultural products including cereals and forages intended for animal feed:

aflatoxins

ochratoxin A

T-2 toxin

Zearalenone

Fumonisions

Mycotoxins cause significant teratogenesis and reproductive toxicity in veterinary species by disrupting endocrine balance, cellular signaling, and embryonic development

Aflatoxins

source: aspergillus flavus and a parasiticus

aflatoxins AFB1, AFB2, AFG1, AFG2, AFB! is a potent mycotoxin

infects the crops and feed ingredients such as corn, peanut, peanut meal, cottonseed, and cottonseed meal

Aflatoxin B1

Fumonisin B1

Zearalenone

Trichothecenes

Endophyte toxicity- fescue toxicosis

Drugs that cause reproductive toxicity