Mare Response to Endometritis Treatment

When treating breeding-induced endometritis, lavage (flushing) and low doses of oxytocin can help the uterus clear the inflammation, Troedsson explained.

Photo: Lee Thomas

In September Mats Troedsson, DVM, PhD, Dipl. ACT, ECAR, professor and director of the University of Kentucky (UK) Gluck Equine Research Center and chair of the department of veterinary science, lectured at UK's Veterinary Diagnostic Laboratory (UKVDL) on endometritis.

"Endometritis is a fine-tuned interaction between the host immune system and invading agent for which targeted treatment works best," he said. "It is important to distinguish between 'normal' and 'abnormal' mares, since only 10-15% of broodmares are susceptible to persistent endometritis."

Endometritis is an inflammation of the uterus lining that can be caused by breeding or introducing bacteria into the uterus. Typically, endometritis resolves quickly, but in some mares chronic, recurrent uterine inflammation is a persistent problem that can interfere with pregnancy.

"While most young mares have a remarkable ability to clear inflammation, older, multiparous (having foaled two or more times) mares can fail to clear contaminants from the uterus and are considered 'susceptible,' " Troedsson said.

Several issues can contribute to susceptibility. Impaired myoelectrical activity (electrical activity in the muscle) or other uterine pathologies, for instance, can delay uterine clearance (Woodward et al). Horizontal uterine placement allows the mare to more readily clear pathogens than pendulous (i.e., downward facing, or slanted) uterine placement. In studies, susceptible mares accumulated nitric oxide following induced inflammation, which impairs smooth muscle contraction, thereby inhibiting uterine clearance, Troedsson said.

"Recent data from our laboratory suggest that the innate immunity may play an additional role in the development of susceptibility to persistent endometritis," Troedsson said. "It is not clear at this time, however, how cytokine (inflammatory mediator) expression and impaired uterine contractility are connected. More research in this area is needed."

Breeding-Induced Endometritis

Breeding-induced endometritis is normal and serves to clear the uterus of excess semen and contaminants, Troedsson explained. During this transient inflammation, which most mares resolve in 24-36 hours, there is a quick expulsion of sperm from the uterus. If not resolved in a timely fashion, the inflammation will create a uterine environment that is harmful to the embryo and often results in pregnancy loss.

With persistent breeding-induced endometritis:

  • Uterine contractility is impaired, resulting in delayed uterine clearance;
  • Impaired cytokine modulation appears to play a role in susceptibility; and
  • Six hours is the critical timeframe to clear breeding-induced endometritis.

When treating breeding-induced endometritis, lavage (flushing) and low doses of oxytocin can help the uterus clear the inflammation, Troedsson explained. Low doses of oxytocin (5-20 units) result in beneficial muscle contraction, whereas higher doses (30-40 units) result in a disadvantageous muscle cramp.

Use of prostaglandin F2α rather than oxytocin has also been shown to aid uterine clearance. If administered after ovulation, however, this treatment could be detrimental to fertility by delaying corpus luteum (an ovarian follicle after discharge of the egg that secretes the hormone progesterone) development.

"With prostaglandin, we are administering it to treat fertility, but we have found it may reduce the chance of pregnancy if given at the wrong time," Troedsson said.

According to Troedsson, causal agents of infectious endometritis include:

  • Streptococcus equi sp zooepidemicus
  • Escherichia coli
  • Pseudomonas aeruginosa
  • Klebsiella pneumoniae
  • Taylorella equigenitalis

In bacterial infections:

  • There is an increased endometrial gene expression of cytokines that helps to clear the infection;
  • There are imbalanced cytokine responses to infection in susceptible mares; and
  • Cytokine response might differ in response to infection and breeding.

"To treat infectious endometritis, you must treat the underlying breakdown of uterine defense and administer antibiotics," Troedsson said. "Most mares respond well to antibiotic treatment, which includes intrauterine infusion, systemic treatment, or both.

"Some mares develop recurrent endometritis, which can be very resistant to antibiotics," he continued. "One theory is that the infectious agent is protected by a biofilm, a group of microorganisms growing on a solid substrate that are resistant to antibiotics. For a treatment to be effective, it must break down the biofilm. Although the endometrium is a likely environment for bacteria to build up a biofilm, it has not yet been proven. Another cause may be the presence of dormant bacteria in the endometrium."

This has been demonstrated by Danish researchers and suggested to be a cause of persistent endometritis.

Both the immunostimulant Settle and corticosteroids had a significant effect on clearing uterine pathogens. The effect of treatment on endometrial cytokine expression was less clear, and the mechanism is still unknown with regards to these and other alternative treatments.

Troedsson explained that several teams at universities around the world are currently researching the underlying causes and best treatment options for the 10% of susceptible mares who suffer from persistent endometritis.

"Ongoing research contributes to the body of knowledge, but the causative agents and best treatments remain ill-defined," he said. "There is a gray zone between resistance and susceptibility to endometritis."

Karin Pekarchik is an editorial officer in UK's Agricultural Communications Services.

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