Equis ISSN 2398-2977

Reproduction: persistent post-breeding endometritis

Synonym(s): Susceptible mare, Problem mare

Contributor(s): Madeleine L H Campbell, Philippa O'Brien

Introduction

  • Cause: failure of the normal physiological mechanisms for eliminating sperm cells and inflammatory products / debris following breeding (natural cover or AI). This failure consists of both under-activation and uncontrolled activation of normal physiological pathways.
  • Signs: intrauterine fluid accumulation detected upon ultrasonography after breeding, which if untreated persists beyond 24-48 h after breeding.
  • Diagnosis: ultrasonographical examination of the reproductive tract; supportive endometrial cytology and bacteriology and palpation of the reproductive tract (per rectum and per vaginum) to help identify underlying causes.
  • Treatment: address pre-existing problems, eg bacterial endometritis Uterus: endometritis - bacterial, prior to breeding. Limit insult to the uterus by breeding only once per estrous cycle. Then, depending on underlying cause: agents to make the uterus contract; cervical dilation; intrauterine or systemic antibiotics, immunomodulation; exercise to promote uterine clearance.
  • Prognosis: depends upon underlying cause. Prognosis improved by prompt recognition of the susceptibility of mares to persistent post-breeding endometritis, accurate diagnosis of the underlying cause, and aggressive early treatment.

Pathogenesis

Etiology

  • In order to understand the etiology of persistent post-breeding endometritis, it is necessary to understand the normal physiological mechanisms which occur in the mare’s uterus following breeding, since persistent post-breeding endometritis is the failure (either underactivation or uncontrolled activation) of these mechanisms.
  • Following breeding, mares need to eliminate those sperm cells which do not pass through the utero-tubal junction into the oviduct and other debris from the uterus, in order to leave the uterus in a non-inflamed state, ready to receive the embryo when it descends into the uterus from the oviduct 5.5-6 days post-ovulation.
  • This clearance is normally achieved by a combination of lymphatic drainage, myometrial contractions (physical expulsion), and a non-specific immune response (necessary because a specific immune response with a memory would have a detrimental effect the fertility of any subsequent breedings).
  • Thus all mares undergo a transient inflammatory reaction within the uterus (endometritis) following breeding - this is a normal physiological mechanism. The inflammation is triggered by sperm cells, which activate complement in uterine secretions. This causes complement factor C5 to cleave into C5a and C5b. This cleavage acts as a chemotactic signal to polymorphonuclear leukocytes (PMNs), causing an influx of PMNs into the uterine lumen Polymorphonuclear (PMN) score table.
  • These activated PMNs bind to sperm cells, by ligand binding and possibly also by extruding their (the PMNs’) DNA to form extracellular neutrophil traps (NET). The PMNs phagocytose sperm cells and bacterial contaminants from breeding.
  • It is proposed that the activated PMNs also release prostaglandin F2α, which promotes myometrial contractions, thus physically removing inflammatory products and fluid from the uterus.
  • In normal mares, the inflammation (endometritis) subsequently subsides. Seminal plasma (i.e. the non-sperm and non-gel component of the ejaculate) has a role to play in limiting the duration of physiological post-breeding endometritis by suppressing complement activation, PMN chemotaxis and phagocytosis.
  • The use of spermatozoa with reduced seminal plasma (as in frozen/thawed semen or sperm 'packed' from fresh semen by centrifugation) results in a more marked and prolonged inflammatory response, because seminal plasma is a modulator of sperm-induced inflammation and protects viable spermatozoa from opsonization and phagocytosis.
  • In mares which are susceptible to persistent post-breeding endometritis (around 10-15% of broodmares), some part of this normal physiological mechanism of post-breeding inflammation, physical clearance and subsequent dampening of the inflammation fails (see Pathophysiology below).

Predisposing factors

General

  • Older mare, either maiden or pluriparous.
  • Mares bred with frozen/thawed semen.

Specific

  • Cervix which fails to dilate during estrus Cervix: fibrosis.
  • Pendulous uterus.
  • Failure of myometrial contractility, ie failure of physical clearance of intrauterine fluid.
  • Failure of normal suppression of normal physiological inflammatory reaction to breeding.
  • Poor lymphatic drainage, eg due to endometrial degeneration/fibrosis Endometrium: fibrosis.
  • Possibly, angiosis, ie endometrial vascular degeneration.

Pathophysiology

  • In mares which are susceptible to persistent post-breeding endometritis, one or a combination of the following factors results in a failure of the normal physiological mechanism for dealing with the insult to the uterus which breeding represents:
  • Failure of physical clearance mechanisms
    • Pendulous uterus meaning that intrauterine fluid cannot be moved towards the cervix by the contracting myometrium, due to gravity.
    • Lack of myometrial contractility.
  • Failure of suppression of the normal inflammatory reaction to breeding, by 24-48 h post-breeding.
There is no evidence that there is a failure of the normal, physiological, initial post-breeding inflammatory mechanism in ‘susceptible’ mares  - the failure is rather one of that mechanism not subsiding by 24-48 h post-breeding.
  • There is an inter-relationship between disruption of normal mechanisms of inflammation and myometrial contractility. During inflammation, nitric oxide is synthesized by inducible nitric oxide synthase. In mares susceptible to persistent post breeding endometritis, there is an increase in NO production following breeding compared to non-susceptible mares. Nitric oxide has a relaxing effect on smooth muscle, ie inhibits myometrial contractility.
  • Prolonged inflammation and prostaglandin release can cause premature lysis of the corpus luteum with resulting progesterone deficiency and embryo mortality.
  • The persistent inflammatory reaction within the uterus and the failure of normal physical clearance combine to set up a vicious cycle of intra-uterine fluid-production. The persistence of intrauterine fluid can:
    • Act as a culture medium for bacteria introduced into the uterus prior to breeding, eg due to poor perineal conformation, at the time of breeding, or post-breeding, eg during the course of intrauterine treatments. Thus, what is primarily a disruption of normal physiological mechanisms can exacerbate or progress into bacterial endometritis Uterus: endometritis – bacterial.
    • Possibly, result in a failure of a mucociliary clearance mechanism which usually promotes uterine clearance post-breeding, by overhydrating the mucus, thus disrupting its viscosity and elasticity and preventing it from functioning normally to traps particles and facilitate their clearance via carriage by ciliary cells.

Timecourse

  • Post-breeding endometritis is initiated within 30 min of breeding.
  • In normal mares, it is self-limiting by 24-48 h post-breeding
  • In ‘susceptible’ mares, it continues beyond this time frame and may persist until the embryo descends into the uterus at 5.5-6 days post-ovulation.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed Papers

  • Recent references from PubMed and VetMedResource.
  • Canisso I F, Stewart J & Coutinho da Silva M A (2016) Endometritis: managing persisitent post-breeding endometritis. Vet Clin North Am Equine Pract 32 (3), 465-480 PubMed.
  • Reghini M F et al (2016) Inflammatory response in chronic degenerative endometritis mares treated with platelet-rich plasma. Theriogenology 86, 516-522 PubMed.
  • Woodward E M et al (2015) Inflammatory mechanisms of endometritis. Equine Vet J 47 (4), 384-389 PubMed.
  • Bucca S et al (2008) The use of dexamethasone administered to mares at breeding time in the modulation of persistent post-breeding induced endometritis. Theriogenology 70, 1093-2000 PubMed.
  • Maischberger E, Irwin J, Carrington S & Duggan V (2008) Equine post-breeding endometritis: A review. Ir Vet J 61 (3), 163-8 PubMed.
  • Fumoso E A et al (2007) Immune parameters in mares resistant and susceptible to persistent post-breeding endometritis: effects of immunomodulation. Vet Immunol Immunopath 118, 30-39 PubMed.
  • Causey R C (2006) Making sense of equine uterine infections: The many faces of physical clearance. Vet J 172, 402-421 PubMed.
  • Troeddson et al (2005) Components in seminal plasma regulating sperm transport and elimination. Anim Reprod Sci 89, 171-186 PubMed.
  • Trodesson M H T et al (2001) Effect of periovulatory prostanglandin F2α on pregnancy rates and luteal function in the mare. Theriogenology 55, 1891-1899 PubMed.
  • LeBlanc M M et al (1998) Differences in uterine position of reproductively normal mares and those with delayed uterine clearance detected by scintigraphy Theriogenology 50, 49-54 PubMed.
  • Troeddson M H T (1997) Therapeutic considerations for mating-induced endometritis. Pferdeheilkunde 13, 516-520 VetMedResource.
  • Pycock J F & Newcombe J R (1996) Assessment of the effect of three treatments to remove intrauterine fluid on pregnancy rates in the mare. Vet Rec 138, 320-323 PubMed.
  • Katila T (1995) Onset and duration of uterine inflammatory response of mares after insemination with fresh semen. Biol Reprod Mono 1 (6), 515-517 FAO Agris.
  • Troedsson M H T (1995) Uterine response to semen deposition in the mare. In: Proc Society of Theriogenology. San Antonio, Texas, USA. pp 130-135 Scopus.
  • Kotlainen T, Huhtinen M & Katila T (1994) Sperm induced leucocytosis in the equine uterus. Theriogenology 41, 629-636 PubMed.


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