Endometrial Cups Appear to Play a Role in Mare Reproductive Loss Syndrome

For an unknown reason, hundreds of mares in central Kentucky have lost their pregnancies. The syndrome, named the Mare Reproductive Loss Syndrome (MRLS), is costing the thoroughbred breeding industry hundreds of millions of dollars.

To determine how to best help out in the crisis, Dietrich H. Volkmann, BVSC, MMed Vet visited Kentucky in May 2001.

"I became aware of the lack of specific investigations aimed at characterizing the hormonal profiles of mares that had lost their fetuses during early pregnancy," says Volkmann.

He learned that mares that had begun forming their placentas, which occurs at about 35 days after ovulation, were at much higher risk of losing their pregnancy than mares that had not progressed to that stage in their pregnancies. Of particular interest was that although mares were losing their fetuses, most were retaining their endometrial cups.

Endometrial cups are unique glands that develop only in equine pregnancies and, although they are formed by fetal tissue, their survival is independent of the fetus's survival. Several weeks after conception, as the placenta develops, the cups begin to form and produce the hormone equine chorionic gonadotropin (eCG), which can be detected in high concentrations in the mare's blood.

One function of eCG is to stimulate the ovaries to produce additional (accessory) corpus luteums. If a pregnancy is lost during the stage when the cups are present, this stimulatory effect on the ovaries continues with unabated force, preventing the mare from returning to regular heat cycles.

"The result is that the mare can't be rebred again that season," Volkmann points out. "Not only is this a major problem with MRLS, but it also occurs on a regular basis in smaller numbers when mares suffer fetal losses during the endometrial cup phase and cannot be rebred."

In normal pregnancies the endometrial cups are destroyed by an as yet ill-defined mechanism once the mare is between 70 and 80 days pregnant and her eCG concentrations fall to basal levels. This allows the mare that has lost her pregnancy to return to regular cycles only about 120 days after the original conception.

With a new grant from the Harry M. Zweig Memorial Fund, Volkmann is setting out to characterize the hormonal patterns associated with these early pregnancy losses. He hopes to confirm or reject assumptions now held about the behavior of endometrial cups after pregnancy loss, as well as glean crucial information regarding the mechanisms that lead up to pregnancy losses in mares.

"For example, by using hormone production as an indicator of fetal and placental well-being or disease, we may be able to predict whether mares that show some abnormalities in their placental function will return to normal or continue to be high risk," Volkmann points out. "We also may be able to predict whether the fetuses that survive MRLS-related abnormalities will be normal or abnormal at birth."

He will compare hormone levels in blood from normal pregnant mares and affected mares at similar stages of pregnancy. Such an endocrine analysis hopefully will determine whether the corpus luteum, the endometrium, or the placenta initially malfunctioned and caused the demise of the pregnancy.

The grant also will allow Volkmann to examine in detail why some mares that had lost pregnancies as a result of MRLS, and presumably retained their endometrial cups, were still able to ovulate and conceive while most cannot. To do so, he will compare the hormonal patterns of successfully rebred mares with those unsuccessfully rebred. He also hopes to identify some hormones that could be used to treat mares to return them to a breedable status.

"In an attempt to return these mares to a fertile status, we also plan to test a novel approach that manipulates the effect of eCG on the ovaries by injecting mares that have lost their pregnancies but retained their endometrial cups with a highly specific monoclonal antibody against eCG, which is available for use in cattle," Volkmann says.

Although some veterinarians now try to surgically obliterate the endometrial cups in an attempt to destroy the source of eCG so that the mares can be rebred, the injections may neutralize the circulating eCG sufficiently so that the mares can ovulate. Volkmann hopes to determine whether the injections will affect the health of the mares and whether subsequent pregnancies will be normal, considering that the mare still has active endometrial cups from the very beginning of her first pregnancy.

Studying mares that are successfully rebred also will help determine whether MRLS has any long-term deleterious effects on placental function or fetal well-being in mares whose pregnancies were abnormal, and yet the fetus still survived.