Environmental Causes of Congenital and Inherited Anomalies in Animals

In addition to viral infections (see Viral Causes of Congenital and Inherited Anomalies), environmental teratogens include the following:

• plant toxins

• drugs

• trace elements

• nutritional deficiencies and excesses

• physical agents such as irradiation, hyperthermia, uterine positioning, or pressure during rectal examination for pregnancy

Although defects in neonates that are caused by environmental teratogens can resemble or mimic heritable defects, they do not follow a familial pattern. Specific causes can be difficult to identify; however, they often exhibit seasonal patterns associated with growth characteristics of toxic plants or the availability of suitable vectors of arthropod-borne viruses.

Congenital anomalies might follow maternal disease that is due to plant intoxication or viral infection; however, teratogenic effects sometimes occur in the absence of observed clinical signs in the dam.

Biologically active products produced by many plants are known to be teratogens. Ingestion can result in abortion, birth of nonviable neonates, or production of neonates that are abnormal at birth. Production losses can be appreciable if many animals gain access to affected plants at critical times in embryonic or fetal development.

Veratrum californicum (skunk cabbage) has been implicated as a cause of fetal gigantism, prolonged gestation, and craniofacial deformities in sheep that graze rangelands containing the plant. Cyclopamine, a steroidal alkaloidal compound produced by the plant, is the teratogenic agent.

Experimental dosing with cyclopamine in ewes on day 13–15 of pregnancy can cause a variety of congenital anomalies. Ingestion on day 14 specifically induces synophthalmia or a cyclopean defect. Ewes exposed later in gestation might deliver healthy lambs, illustrating the critical interaction of time of exposure and gestational age.

In cattle, ingestion of several species of lupines( Lupinus sericeus, L caudatus, L leucophyllus, L formosus, and L sulphureus) has resulted in “crooked calf disease,” characterized by joint contractures; torticollis, scoliosis or kyphosis; cleft palate; or combinations of these defects. The quinolizidine alkaloid anagyrine is identified as the teratogen, and the critical window for exposure is 40–70 days of gestational age.

Ingestion of L formosus causes similar skeletal defects and cleft palate in cattle and goats; the teratogen is the alkaloid piperidine. With either toxin (anagyrine or piperidine), defects are thought to be related to alkaloidal toxin–induced inhibition of fetal movement during critical gestational periods. Periodic losses due to lupine-induced crooked calf disease occur in the western US after ingestion by cattle on rangeland.

Ingestion of Conium maculatum (poison hemlock) causes contracture defects and occasionally cleft palate in cattle, goats, sheep, and pigs. Both the plant and the seed contain the teratogenic alkaloidal toxin coniine.

Ingestion of Nicotiana tabacum (cultivated tobacco) produces skeletal defects in pigs similar to those induced in cattle and pigs by Lupinus spp and C maculatum. Because of changes in swine management, congenital amelia and hemimelia in piglets that once occurred when pregnant sows were allowed access to tobacco stalks are rare today. Ingestion of Nicotiana glauca (tree tobacco) also induces contracture defects and cleft palate in cattle, sheep, and goats.

Other plants suspected of causing similar defects in calves include Senecio spp,Cycadales, Blighia spp,Papaveraceae, Colchicum spp, Vinca spp, and Indigofera spicata and related plants. Sudan grass (Sorghum bicolor) has been incriminated as a cause of congenital joint contracture in horses, and Johnson grass (Sorghum halepense) can cause arthrogryposis in calves.

Pregnant mares that consume fescue pasture or fescue hay infected with the fungal endophyte Epichloë coenophiala (formerly Neotyphodium coenophialum) are at risk of abortion, prolonged gestation, hypogalactia, and delivery of weak or dysmature foals. Ergovaline and other ergot alkaloids produced by the endophyte are the cause of fescue toxicosis. Endophyte-free fescue and fescue infected by nontoxic endophyte strains reportedly can be grazed safely by pregnant mares.

Congenital hypothyroidism in foals has been linked to increases of dietary nitrate concentrations in pregnant mares in western Canada and to dietary exposure of late-gestation mares to E coenophiala–infected fescue.

Pesticides, herbicides, pharmaceutical agents, and other chemicals have been incriminated as teratogenic agents. Drugs and chemicals undergoing approval processes in the US, Canada, and many other countries must be tested for teratogenic potential before commercial licensing.

Some products are labeled with instructions to specifically avoid use in animals that are pregnant or might be pregnant. Other products might be labeled as safe for pregnant animals after the fetus exceeds a specified gestational age.

When using some herbicides, it might be necessary to withhold animals from pasture for specified periods after application.

Extralabel use of pharmaceutical agents in pregnant animals and inadvertent exposure to pesticides and other chemicals carries inherent risks, including adverse effects on the developing fetus.

Veterinarians and producers should be aware of the potential for pregnancy loss or development of congenital anomalies after administration of therapeutic agents or exposure to pesticides and chemicals and should exercise appropriate caution when using such products.