Spring 2009

Since 1967, Royal Canin has been at the forefront of developing innovative nutritional responses in the field of dog breeding. Even if nutrition is fundamental in breeding, it cannot give all the keys for success. Application of reproduction techniques is the deciding factor.

Breeder's Handbook: Fetal Development and Birth Defects in Dogs

As soon as fertilization occurs within the oviducts, genetic programming takes over. A chemical reaction, triggered by the penetration of a sperm into the cytoplasm of the egg, causes the outer covering to bind the surface, preventing another sperm from imbedding. After approximately 12 hours the first cellular division occurs, beginning the miraculous creation of a puppy. The divisions repeat every 12 hours, until at the 16-cell stage has migrated to the uterine horn.

The picture shows the equivalent of a litter of puppies, in the very early post-fertilization stage. “Cellular Divisions After Fertilization” courtesy Elise Malandaine, Royal Canin, France

The first 8 cells created are undifferentiated, meaning that they each have the potential to become any cell type necessary in the developing embryo. Only 3 of these cells are necessary to grow an entire embryo, which will continue to develop through the fetal stage, into a puppy.

After the 8-cell stage, the cells begin to differentiate into 3 main types, from which every organ and specialized cell will result. At the time the 16-cell mass reaches the safety of the uterus, it enters the active embryo stage. Within two weeks the embryo will find a place of its own in the uterus where it will implant into the uterine tissues, and begin to form a placenta.

Placenta Stage
The placenta is an organ all by itself, with a very specialized mission. It not only provides nutrients from the mother’s blood to the embryos, but also delivers oxygen. It also transfers the waste products from cellular metabolism of the embryo back to the maternal blood, to be excreted. The mother’s blood and the embryo’s blood never mix; each is encased in its own blood vessels, but they come into such close proximity through capillaries that the nutrients, oxygen, metabolic waste, and carbon dioxide can pass from one set to the other.

The placenta is a joint effort between the mother and baby, each developing a rich nest of blood vessels and supporting tissues that interconnect to create a whole.
Aside from these functions, the placenta also anchors the embryo within the uterus to protect it from the mother’s movement. Unlike the structure of some other animals, the placenta in dogs and cats is like a cigar wrapper “ring” that circles the embryo, maximizing its function.

Embryo Stage
The embryo stage lasts for about 30 days and is marked by the differentiation of the early cells into general cell types, which will further specialize mid-gestation. The simplest origins of all specialized cells begin in three layers of the early embryo. The endoderm is the layer of cells to the interior and is destined to become mucosal membranes (lining of the mouth, inner surface of eyelids, lining the nostrils, etc.), and the respiratory and digestive systems.

The next layer of the embryonic mass is the mesoderm, or middle layer. From this primordial layer the muscles, connective tissue, bone, circulatory system, urinary system and genital system will emerge. The outermost layer of cells, the ectoderm, will develop into the outermost layers of skin, with hair follicles and sebaceous glands. It will also differentiate into nervous-system tissues including the eyes, brain, spinal cord, and peripheral nerves. Finally, it further specializes into the sensory organs for sight, sound, balance, tactile sensation, and pain receptors.

The embryo develops each successive level generally from the head end first, extending through the chest region and abdomen, and then the pelvic area, gradually finishing with the tail and tail-end structures. With the rapid growth of cellular mass, the embryo will quickly outgrow its ability to feed all its cells by simple diffusion, making it necessary for a rudimentary heart to help move blood throughout the embryo.

Fetal Stage
The neural system, which includes the brain, nerves and spinal cord, is among the first of the body systems to specialize in the fetus. It is also one of the last systems to complete its formation. Dogs and cats are born before their nervous system is fully functional, and will reach 6 weeks of age by the time the tissues mature.

The limbs grow, forming the shoulders and hips first, then the forelegs and thighs, and finally the lower legs and paws. The paws develop as paddles, with the separate toes becoming independent due to the degradation of the tissues between. As joints begin to develop, it is important that they are moved to prevent becoming fixed in place. Congenital limb deformities can result, which can also lead to birthing problems if the legs can’t flex to accommodate the cervix and birthing canal at whelping.

The head forms as two distinct sections, the face and the cranium.

Each has a different origin of embryonic tissue. Because of this, they may be impacted independently by genetics or teratogens (substances that cause birth defects). It is easier to understand the formation of brachycephalic faces (short-nosed or flattened face) knowing that the face forms independently of the skull.

As the lungs develop, they are filled with liquid to maintain a constant pressure. Since they will not be used to oxygenate blood until after birth, most of the fetal blood flow will bypass the lungs. Once the puppy is born, the fluid in the lungs is discharged and new airsacs (alveoli) form within the lungs.

There are three structures unique to the fetus that should degenerate within a few days after birth. The structures are important to protect the lungs and liver of the evolving fetus, but unnecessary and potentially damaging after the pup is a few days old. The anatomic features specific to fetal development are the foramen ovale in the heart, the ductus arteriosus between the pulmonary vein and the aorta, and the ductus venosus redirecting blood flow around the liver.

Just as the fetal lung tissue doesn’t need the full extent of blood flow from the heart during gestation, neither does the liver. The dam’s liver fully detoxifies the blood for both her and the unborn puppies.

Potential Birth Defects
At birth, changes in blood pressure and oxygenation trigger the closure of these protective fetal structures under normal circumstances. Occasionally, these structures persist after birth and will cause problems, ranging from mild to severe, even life-threatening.

There are a multitude of potential problems to interfere with embryonic and fetal development. These may be genetic, structural, or environmental in nature. Environmental causes encompass infectious agents, teratogenic drugs and nutritional imbalances. Each organ system has a critical period in its development when it is most at risk. Chemical exposure can include medications, anesthetics, and preventive drugs.

There are approximately 250 genetic diseases in dogs. These are due to the following:

Genetic causes of birth defects, also called congenital defects, can occur from a variety of events. Mutations, or changes in the genetic material (DNA), can result in replication errors. Under normal circumstances, DNA is copied when one cell divides into two. Not surprisingly, there are a myriad of steps involved, as well as numerous substances, that interact with the replication of the genetic code. Any step in the complex process can be interrupted. Mutations may occur from too few components produced, an extra component being interjected, or the correct components being replicated out of sequence. As animals age, these mutations occur more frequently.

Inbreeding can be another cause of genetic malfunction. The degree of inbreeding indicates the concentration of an ever-decreasing genetic pool. This increases the likelihood of homozygous gene inheritance, meaning that any detrimental genes present are more likely to have full affect on the resulting offspring.

Geneticists have established a formula to reflect the degree of inbreeding found in any individual, called an inbreeding coefficient. For an animal that is not inbred at all, that number would be zero. Conversely, for an animal that is completely inbred, the coefficient would be at or near one. The higher the coefficient value, the higher the prevalence of defects, fetal and neonatal death.

To illustrate this, a comparison between a mating of two dogs from different breeds and a mating of dogs within a breed shows a marked increase in neonatal mortality from 3.4 percent (two breeds) to an average of 15 percent (one breed).

Structural birth defects are caused by a primary error in the development of a body part. This could be caused by trauma, malpositioning, or a pharmacologic interference. Approximately 6 percent of pups born will have some type of developmental defect. These will range from very minor (kinked tail tip) to major (cardiovascular anomaly).

A major contributor to congenital defects is the inappropriate use of medicines during pregnancy. Drugs that one wouldn’t automatically suspect of potentially having such side-effects include some antibiotics, deworming or antiparasitic compounds such as sulfadimethoxine (Albon) and metronidazole (Flagyl), antifungals given orally, and even some diarrhea treatments.
There are infectious agents (bacteria, viruses, parasites) that can trigger developmental defects. Among these are both types of canine parvovirus, the traditionally recognized type 2 manifesting as hemorrhagic diarrhea; and type 1, also known as the Minute virus. As far as parasites, toxoplasmosis is a disease condition that frequently results in defects.

Cleft palates may affect a number of puppies in the same litter, particularly in brachycephalic breeds. Supplementation with folic acid at the start of gestation can help in preventing such deformities.

Nutritionally, the most common defect seen may be cleft palates. However, it is important to recognize that cleft palates can result from other causes as well, such as genetic, or use of medications during pregnancy.

Certain breeds have a higher prevalence of cleft palates. This is generally associated with brachycephalic breeds such as Boston Terriers and French Bulldogs. The nutrient usually involved is folic acid, or folate, a B vitamin. Folic acid plays an integral part in DNA replication and translation. If it is not present in adequate levels, the resulting strands of DNA are fragile and break.

It is important to note that levels of folic acid in the diet may not be deficient, and that there is a chemical present that inactivates or blocks folic acid so that it can’t be used in the critical processes.

Another nutrient that can trigger cleft palates is vitamin A. Excessive levels of vitamin A are the problem. The most common cause of hypervitaminosis A is liver supplementation to the regular diet. Vitamin A stores in liver tissue, so food sources rich in vitamin A can accumulate the nutrient in the dog’s liver and in the blood stream. This is just one example when adding a supplemental food to a dog’s diet does much more harm than good. Generally speaking, the best application of nutrition is to feed a complete and balanced dog food, appropriate for the life stage, size and lifestyle, and nothing else.

Congenital defects occur in every breed, and every breeder will have some show up in their dogs. This is normal. However, you can minimize this occurrence by feeding a diet specifically formulated for breeding, breeding animals that have been vaccinated regularly, dewormed regularly, and are healthy; and not administering any drugs during pregnancy unless advised by your veterinarian. Good record keeping can help determine what occurrence of birth defects is within normally expected levels, and what is excessive. It can also help pinpoint any inbreeding issues, genetic predisposition, or inadvisable mating.

For more information on Royal Canin and its nutritional solutions, visit www.royalcanin.us/akc.

Ronald N. Rella, Director, Breeder Services
Email: AKCbreeder@akc.org
Customer Service | Phone: 919-233-9767 | Email: info@akc.org

© The American Kennel Club 2008