Selected Topics in Reproductive Pathology: Mare II

This manuscript will review commonly encountered reproductive pathologic conditions in the non-pregnant and pregnant mare. Conditions include endometritis, placentitis, and retained fetal membranes. 

1. Endometritis

Endometritis, or inflammation of the endometrium, is a condition that is costly and frustrating to mare owners. The condition is most commonly defined as either infectious endometritis or postmatinginduced endometritis and can be caused by the introduction of pathogenic organisms, semen, urine, or air into the uterus. A variety of factors contribute to the development of endometritis, including age, perineal conformation, anatomic abnormalities, poor uterine contractility, defective lymphatic drainage, and degenerative changes in tissues that make up the reproductive organs. Elucidating the root causes of endometritis can be challenging.

Pathophysiology

Because endometritis is a complex condition, the pathophysiology of the disease is as well. Although all mares develop endometritis as a result of breeding,¹  the response to inflammation differs between mares (Fig. 1). Most mares are intrinsically prepared to eliminate contaminants after mating, thus resolving inflammation and preventing infection.²  These mares are termed “resistant” to mating-induced endometritis. Other mares are more prone to developing endometritis, and they are termed “susceptible.” Mares that are deemed resistant to endometritis have intact mechanisms for uterine clearance of contaminants after breeding via mechanical evacuation of uterine contents as well as lymphatic drainage. Mares that are susceptible to endometritis suffer one or more defects in the system such as an anatomic abnormality, impaired mechanical or lymphatic evacuation of the uterus, or compromised immunologic response to inflammation. Under inflamed conditions, resident bacteria become opportunists and infection ensues. Therefore, endometritis is further subcategorized as infectious³  or postmating-induced endometritis. In some instances, both conditions coexist. To properly diagnose and treat endometritis, risk factors common to all types of endometritis must be examined.
 

Risk Factors

Risk factors for endometritis include mare age and parity, perineal and birth canal conformation, clearance of contaminants, and immune response to antigenic stimuli. Pluriparous mares frequently experience trauma during delivery that can affect the uterus or anatomical barriers to uterine infection, including the vulva, vestibule-vaginal sphincter, and cervix. Aberrations in reproductive anatomy provide an opportunity for air, urine, and bacteria to contaminate and colonize the reproductive tract. If the mare is free of other conditions, such as dependent uterine position or impaired lymphatic drainage, she may be able to clear herself of any contamination and inflammation. However, older mares often experience overall conformational abnormalities that affect uterine position, uterine contraction, and lymphatic drainage.^4,5 These mares are prone to developing pendulous uteri that fail to evacuate contents.⁴ Resulting inflammatory responses lead to luminal fluid production and accumulation. In addition, uterine dependency can result in persistent urine pooling or pneumouterus, particularly during the postpartum period. Aged/susceptible mares also often suffer from defects in lymphatic drainage⁶ that compounds fluid accumulation during the periovulatory period. These factors lead to a compromised uterine environment and thus make the mare more susceptible to uterine infection.

More recently, the role of mucus production^7,8 and the presence of biofilm have been examined in persistent uterine infections (Fig. 2).⁹ Mucus can both aid and impair pathogen clearance in systems with a mucociliary apparatus. It has been postulated that normal mucus production facilitates cilia-propelled removal of contaminants from the uterus after breeding.⁸ Under persistently inflamed conditions, excess or reduced mucus production alters mucociliary function and impairs pathogen clearance. Excess mucus production has been identified in mares with chronic endometritis⁷ and has been specifically associated with microorganisms (Escherichia coli and ß-hemolytic Streptococcus).¹⁰ Biofilm has similarly been postulated to contribute to conditions that favor bacterial proliferation in the uterus of some mares. Under natural conditions, bacteria exist in either a free-floating (planktonic)¹¹ or sessile (adhered) state. The free-floating form allows bacteria to proliferate and grow, whereas the sessile state promotes persistence and long-term survival. The formation of a biofilm is a complex process that allows a bacterial population to transition from planktonic to sessile states, thus promoting survival. Through the formation of biofilm, bacteria are enclosed in a biopolymer matrix that allows them to be adherent to inert surfaces (table tops, glassware, vascular catheters, orthopedic prosthetic devices, etc.) or to each other. Once attached, bacteria grow and produce extracellular polymers¹² that facilitate long-term survival of the sessile bacterial cells. In addition, the host produces antibodies to the bacteria (both planktonic and sessile), but the immune response eliminates the planktonic bacteria only. Sessile bacterial antigens, although recognized, are impenetrable within the extracellular polymeric substance (EPS) layer of biofilm. As a result, general immune responses to pathogenic bacteria are diminished when biofilm is present. In addition, antimicrobial susceptibility is affected by biofilm production.⁹ The thick EPS layer as well as proteins and lipids provide an effective barrier for antimicrobial penetration of sessile bacteria. Disease symptoms are often ameliorated after antimicrobial-induced death of planktonic bacteria, but infection persists after treatment because the sessile bacterial population is protected by the biofilm. Recent data confirm biofilm production by bacteria (E. coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae) isolated from the equine uterus.¹³ 
 

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