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Teratogens and the Pregnant Mare

Mirror KB Equine Article Series


Teratogens and the Pregnant Mare

By Kim and Kari Baker


There are few instances more devastating in the equine world than to breed for the horse of your dreams only to have the resulting foal born with a birth defect that seriously threatens its chance of enjoying a performance career, besides possibly putting its life in danger.

At one time, it was thought that the majority of anomalies present at birth were genetic in origin. However, more recent knowledge tells us that many are the result of environmental teratogenic actions that work either alone or in combination with genetic factors.


Genetic messages do direct and monitor the growth of the embryo and fetus, but the developmental process can easily be influenced or disrupted by environmental teratogens.  “Teratogens are compounds, either natural or man-made, that in the environment of the dam, in a sufficient dose and at the right time, can produce an abnormality in the fetus,” says Veterinary Toxicologist Petra Volmer DVM of the University of Illinois.

A vast number of environmental teratogenic agents that are potentially harmful to the equine fetus can include chemicals and noxious plants, as well as many therapeutic drugs and herbal remedies.  In addition, nutritional deficiencies or excesses may have adverse effects on a foal.  Maternal health factors such as inadequate levels of oxygen transfer across the placenta, infections, hyperthermia, and fetal positioning may also have negative effects in utero.

In spite of the fact that more than 80 congenital defects have been identified in the horse, discovering the causes has been no easy task.  It is typically very difficult to determine what event(s) may have resulted in an anomaly since information on the exact day or week of gestation when a mare was in contact with a possible teratogen is rarely available.

To make things even more complicated, exposure to a single substance might cause a wide range of effects in different foals since a teratogen capable of acting at different stages of gestation might bring about a variety of anomalies at each exposure in relation to a foal’s gestational age.

In this same light, if more than one environmental factor is involved, their relationship may also have a significant impact on the type or severity of the resulting abnormality.

Fetal Environment

Cradled by layers of tissue that make up the placenta, the developing fetus is at the same time well protected, yet quite vulnerable.  There was a time when it was believed that the placental membrane provided an effective barrier that could prevent the passage of noxious substances and limit microorganisms from reaching the embryo or fetus. Yet, recent evidence suggests that many compounds may be capable of crossing the placental barrier.

Though the placenta is able to screen many substances on the basis of size, molecules small enough to pass through the gastrointestinal tract are, for the most part, able to cross the placental barrier as well.  Infectious organisms can also reach the developing fetus through the cervix as a result of poor techniques in the breeding shed as well as unhygienic examination procedures.  Once these organisms have invaded the fetal environment, they may persist throughout gestation, interfering with normal growth and development.

Then too, maternal health factors such as ongoing stress, age and whether or not she has borne a number of foals may affect the health of the placenta, which may in turn result in an increased risk to the fetus due to environmental insults.

Time of Exposure

The timing of the teratogenic exposure to the embryo or fetus, may well determine what the toxic agent’s final effect will be on the foal.  Most developmental anomalies occur within the first six weeks of pregnancy, during the embryonic stage.  “This is considered the most critical period, because organogenesis occurs during this time,” says Dr. Volmer.

During this period of rapid growth and development, cells are open to teratogenic actions that may result in abnormalities by damaging the cells, by altering the cell’s normal growth pattern or by arresting cell growth all together.  Because these causative agents are capable of affecting many organs and systems at this stage, the pattern of abnormalities will depend upon which tissues or systems are differentiating at the time of exposure.

As the pregnancy progresses the susceptibility of the fetus to various agents changes.  This period, known as the fetal stage, is when growth and functional maturation of organs and systems already formed, occurs.

Rather than structural anomalies, teratogenic exposure at this time is more likely to affect overall fetal growth, the size of a specific organ, or the function of an organ.  Though the majority of structural defects are obvious shortly after parturition, functional impairments may not be evident for several days, weeks or even for a number of years following birth.

Incidentally, there are some organ systems, such as the immune system, central nervous system and the cardiovascular, that are sensitive to teratogens throughout gestation.

Furthermore, environmental teratogens can even be responsible for birth anomalies when exposure occurs to the dam or sire before conception.  In some instances, damage to genetic material in the ovary or sperm (mutagenesis) can result in inheritable defects in their offspring.  In other cases, the toxic agent may simply persist in the mare’s body tissues to affect the developing foal following conception.

Additional Factors

The type or severity of a birth defect caused by an environmental teratogen is subject to other factors, such as the specific action of an agent, e.g. type of agent involved may determine the area of the body or which developmental process will be affected.  Equally important factors in determining the severity of a congenital anomaly is the duration or amount of exposure to the fetus and the mare’s over-all health. Other factors that play roles in the final outcome are individual differences in placental membranes, as well as variations in individual maternal and fetal metabolisms as well as genetic susceptibility.

The amount of exposure to the fetus, known as the dose response, simply means that the greater the dose the greater the effect will likely be to the fetus. Keep in mind that dose thresholds for some teratogenic effects are below levels required to cause toxicity in the dam if the agent is indeed toxic to the mare at all.

Then too, if the mare’s liver or kidney function is impaired for any reason, prolonged fetal exposure will result due to the mare’s inability to eliminate the agent from her own circulatory system, hence the foal’s circulatory system.

The mare is capable of metabolizing some teratogenic agents so that the level of exposure to the fetus will be reduced.  However, even in a healthy mare the placental/nutrient exchange system is unable to remove all blood-borne teratogens from the fetal circulation system efficiently. It follows that since the fetal liver is unable to detoxify blood until after birth, teratogens that do cross the placental barrier over an extended length of time will become concentrated in the fetal tissues as gestation progresses.

Medicating the Mare

Keeping the mare healthy is of primary concern during her pregnancy, and while present-day health of most broodmares has improved, the complexity of exposure to environmental teratogens has greatly increased.  Many agents that are potentially harmful to the fetus are encountered in therapeutic drugs, herbal remedies, ointments and pesticides.

It goes without saying that an occasion may arise when the mare may need to be put on medication for the treatment of illness or injury, besides the meting out of inoculations for the prevention of disease and the use of anthelmintics for the removal of internal parasites.

Unfortunately, little is known about what actions the majority of drugs and chemicals used in the horse industry will have on the equine embryo or fetus.  Still, there are strategies to prevent or decrease the risk of fetal anomalies when medications must be given.

Caution should be taken in the use of all drugs and herbal remedies throughout the mare’s pregnancy. In fact, the best policy is to “avoid the use of any medication if possible,” says Dr. Volmer, “unless there is a compelling clinical indication for its use, and then always choose medications that have been proven safe for broodmares and follow label instructions.”

Before administering medications and herbal remedies, including over-the-counter preparations to a pregnant mare, ask a veterinarian about their safety. Drugs which indicate “No information for use in the broodmare is available” on the label ought to be avoided as they are not to be considered safe.

However, that isn’t always possible in all situations, and one must seek to provide maximal safety to the fetus as well as therapeutic benefit to the mare.  Those medications that must be administered should be dispensed for the shortest feasible time.

In a similar vein, use of the lowest medicinal dose, as well as the avoidance of combination drug therapies may well decrease the possibility of risk to the fetus.  Likewise, “completely steering clear of the use of drugs or herbal remedies until after the first trimester when organogenesis occurs, could greatly reduce the potential danger,” adds Dr. Volmer.


Nutritional deficiencies, imbalances, and excesses can also have a teratogenic impact on the mare’s growing fetus, but because the nutrient demands of the embryo are rather low, developmental abnormalities are rare unless the mare is subjected to severe nutrient extremes. When they do occur, the nutrient(s) involved will determine which area(s) of the body or which system will be involved.

In early pregnancy, vitamins and minerals are the most critical nutrients. A vitamin D deficiency may lead to neonatal rickets, while an insufficiency of vitamin A could result in eye defects. If Vitamin E, which is thought to be necessary for the development of the normal ova, is lacking in the diet it’s possible that the ova’s ability to divide may be impacted.

Iodine in either excess or deficiency is known to cause congenital goiter in foals, resulting in abnormalities such as forelimb contracture and Dysmaturity Syndrome.  However, a deficiency of the mineral is quite rare since most salt supplements contain adequate iodine.Congenital hypothyroidism is more often due to an excess of iodine, the result of over-supplementing the mare’s diet with seaweed or kelp products.  The consumption of plants such as Shephards purse, Field pennycress, and Tumble mustard that contain the toxic chemical glucosinolate may also give rise to CHD.

Hypervitaminosis of water soluble vitamins, such as the B vitamins, rarely causes problems.  On the other hand, fat soluble vitamins (A, D, E, and K) can reach toxic levels that may damage the embryo. Of significant concern is vitamin D.  An excess will interfere with the utilization of calcium and phosphorous, resulting in an increase in the occurrence of musculoskeletal anomalies.

Tracking down Teratogens

Though research into environmentally caused teratogenic abnormalities is still in its infancy, it is continuously growing in importance.  The number of chemicals, drugs or other environmental factors that have been proven to be teratogens in horses so far has been relatively small.  Nevertheless, concerns about combinations of agents or chronic exposure to low amounts of substances in an increasingly complex chemical environment are very real. Public awareness of hazardous chemicals used on the farm, as well as the recognition of the teratogenic potential of therapeutic drugs, is essential in narrowing the incidence of birth anomalies.

However, as a rule, the majority of congenital abnormalities that do occur on horse breeding farms are not investigated to determine origin, since life threatening defects are infrequent and milder abnormalities are often missed without a thorough examination. As noted earlier, a functional anomaly may not even reveal itself for several years and by the time it does a teratogenic action may not even be considered.

Granted that the incidence of congenital birth defects in foals is relatively low, estimated to range somewhere between three and four percent of all births, they still have a profound effect on the horse industry. As might be expected, it is with only an abrupt increase in the frequency of a particular anomaly that appears in a geographically localized area or an increase of defects associated with the use of a new drug that horse breeders will generally sound an alarm. Even so, overlooking or even accepting a congenital anomaly, though minor it may be, without an investigation into its cause is an economically unsound practice.

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