Fertilization and Early Pregnancy Loss in Mares

There are many factors that contribute to a mare successfully carrying a foal to term. Early pregnancy loss is widely associated with a mare's age, followed by embryo, oviductal, uterine, or endocrine factors, Ball said.

Photo: Anne M. Eberhardt/The Horse

According to Barry Ball, DVM, PhD, Dipl. ACT, the Albert G. Clay Endowed Chair in equine reproduction at the University of Kentucky's Gluck Equine Research Center, there are a variety of potential causes for pregnancy loss in mares.

Early pregnancy loss is widely associated with a mare's age, followed by embryo, oviductal, uterine, or endocrine factors, Ball said. Older or multiparous (having foaled two or more times) mares have an increased risk of developing abnormal numbers of chromosomes (aneuploidy) presumably due to a prolonged follicular growth.

"As the mare ages, so do her oocytes," Ball said. Thus, the risk of uterine impairment might result from the mare's normal aging processes.

Fertilization in the mare is a fairly complex process:

When the egg matures, the oocyte sheds from the follicle into the oviduct, Ball said. At the time of ovulation, the cumulus cells surrounding the egg undergo a massive expansion to form a sticky cell mass allowing the egg to adhere to the cilia (microscopic hairs) in the oviduct.

The egg then travels down into the fimbria, a fringe of tissue at the oviduct's opening. A glandular structure called the corpus luteum is organized from cells producing the hormone progesterone, which is needed to establish and maintain pregnancy until the placenta comes into function at about 150 days of gestation.

Sperm are transported to the oviduct initiating fertilization prior to ovulation and, in most cases, are stored there for several days. The sperm remain viable for two or three days in the oviduct, while the egg is only viable for about six hours after ovulation, which makes insemination timing vital, Ball said.

The sperm itself is not capable of initiating fertilization until it has been capacitated in the mares' tract over a short period of time.

"The sperm undergoes a biochemical process close to the isthmic oviduct, which acts to both reduce sperm number and enhance the sperm quality," Ball said.

Following capacitation, the sperm acquire a hyperactive motility allowing sperm-egg contact. The next step is the acrosome reaction, which allows the sperm to provide the enzymes required to break through the egg. A cortical reaction normally prevents the egg from further fertilization, but a failure in this signal can cause multiple sperm to fertilize the egg, Ball said.

One of the most important causes of embryo loss during early gestation is post-breeding endometritis (failure of the uterus to clear foreign resulting in inflammation of the inner lining of the uterus). Older mares tend to have a delayed inflammatory response to contaminants, such as semen, but do not show any signs of inflammation other than luminal fluid prior to breeding, Ball said.

The accumulated fluid leads to enhanced inflammation three or four days later, with secondary infection referred to as chronic endometritis, Ball said. Most of these pregnancy losses occur before 20 days of gestation and can also cause fertility-threatening changes, such as periglandular fibrosis (scarring) and uterine lining (endometrium) scarring that affects the embryo's chances of survival, Ball said.

"Always reduce the number of breedings if there is a history of recurrent endometritis," Ball said.

Infectious endometritis results from bacterial invasion into the uterus, such as Streptococcus. The bacteria typically enter multiparous mares with poor vulva conformation that doesn't seal properly and exposes the uterus to bacteria. Acute infectious endometritis might result from impaired uterine defense systems in older mares, which could be compromised over time.

As soon as the egg is fertilized it becomes a zygote, and cell division begins instantly, Ball said. The fertilized embryo remains in the oviduct for six days and then migrates down and enters the uterus.

"Early pregnancy loss in this period, we typically identify as prefixation events from Day 6 to 16," he said. "In this period the embryo is very delicate."

According to Ball, loss often occurs in this period due to an imperfect interaction between the embryo and the uterus failing to send the pregnancy signal, so the mare starts cycling again.

Once the embryo enters the uterus, it expands rapidly and usually becomes fixed (generally at the base of one of the uterine horns) in one spot within the uterus on Day 16 after ovulation. Postfixation events occur from Day 16 and so on, Ball said. The embryo eventually becomes a fetus at about Day 40, when the placenta is usually formed.

Although a mare's age plays a significant role in early pregnancy loss, fertilization timing and early intervention with the aid of modern ultrasound might help decrease its incidence.

Placentitis in Mares

Placentitis (Inflammation of the placenta) is another major cause of late pregnancy loss and has a tremendous economic impact on the horse industry, said Ball. Multiparous or older mares are at particular risk of developing placentitis; however, infection can occur in any age at any time of gestation.

While an affected mare can still deliver a foal, it is likely the foal will be aborted late in gestation or be born with septicemia (blood-borne infection). According to Ball, placentitis was responsible for about 20% of late reproductive loss in a recent study performed in Central Kentucky.

Ascending bacterial infection of the uterus that enters through the vagina is the most common cause of placentitis. Normally it concentrates at the cervical star, but infection can spread throughout the whole placenta, Ball said. Previous foaling might also have injured the cervix, allowing bacteria access to the placenta.

Many types of bacteria can potentially cause placentitis, such as Streptococcus spp. and Escherichia coli that are also found in the vagina of normal mares. Pseudomonas aeruginosa and Klebsiella pneumonia can cause abortion, too. According to Ball, fungal and viral infections are less common causes of placentitis and tend to occur late in pregnancy.

"All organisms that can cause uterine infections can produce placentitis and acute disease in the mare," Ball said.

The inflammation caused by the bacteria stimulates the tissue to produce prostaglandin, which might lead to uterus contraction and premature labor. Clinical signs of placentitis occur acutely or chronically at any time during gestation, Ball said.

The most common visible signs of ascending placentitis are premature udder development and vulvar discharge, whereas subclinical signs include thickness of the placenta and uterus in the area of the cervical star. When the placenta becomes thickened and inflamed, there is an increased likelihood it pulls away from the uterine lining, compromising oxygen and nutrient delivery to the foal, Ball said.

The umbilical cord can also cause abortions, according to Ball. Usually the cord is not much longer than about 80 cm, but in the cases of a longer cord there is an increased risk of strangulation or twists that compromise blood flow to the fetus.

"These abortions normally occur in the last months of pregnancy," Ball said.

Nocardioform placentitis

This variation of placentitis has been associated with sporadic incidences occurring particularly in Central Kentucky and Florida, but horses in South Africa and Italy have also been affected. A number of bacteria such as Crossiella cryophila, Crossiella equi, and Amycolatopsis are thought to cause nocardioform placentitis, but it is not yet fully understood, Ball said. The infected area of the placentitis is usually isolated to a larger area at base of the pregnant horn of the placenta. Affected placentas are usually covered with brown pus.

"This variation is tricky because there are often no clinical signs of the infection," Ball said.

Nocardioform placentitis can cause abortion, stillbirth, or foals born alive but compromised. According to Ball, dry hot summers have been associated with high incidences of nocardioform placentitis. How mares become affected has not been fully determined.

Mare Reproductive Loss Syndrome (MRLS)

A large number of Central Kentucky mares in the early 2000s suffered from mare reproductive loss syndrome (MRLS). Most mares either aborted or had their placenta compromised. The cause of MRLS is not yet fully understood, but it has been suggested that ingestion of the barbed-haired Eastern tent caterpillars might play a role and cause bacterial infection in the mare, Ball said.

Early detection of ascending placentitis is crucial because the visible signs are not always visible and if/when they become visible, it might be too late for treatment. This is why bacterial placentitis can be difficult to treat successfully. Ball said veterinarians often recommend antibiotics to prolong the gestation, but systemic antibiotics are not always effective in controlling the damage to the placenta.

Ultrasonography is an excellent tool for monitoring fetal and placental changes in mares affected by placentitis. The uterine-placenta thickness or separation can be a sign of placentitis. Measuring hormone levels such as progestin concentrations can indicate placental abnormalities at certain stages of gestation, Ball said.

Shaila Sigsgaard is a contributing writer for the Bluegrass Equine Digest.

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