and competition could compromise fertility and embryo quality.3 Oocyte recovery by ovum pick-up (OPU) has the advantage that it can be performed as a one-off, outpatient procedure; moreover, intra- cytoplasmic sperm injection and in vitro embryo production may yield multiple embryos such that there is less need to repeat oocyte recovery ses- sions.4 Nevertheless, OPU is an invasive procedure, and actively competing mares more often suffer postprocedure discomfort, normally for only 1 to 3 days, but occasionally for longer (7 to 10 days). A reasonable proportion of serious breeders pre-


INFLAMMATION, INFECTION, OR BOTH? ROOT CAUSES OF ENDOMETRITIS 4. Breeding-Induced Endometritis


empt the issue of fertility decline during a competitive career by breeding mares when they are 3 to 4years old, before they enter serious training or competition, either to carry a foal or to yield embryos. Clearly, these young mares are ideal candidates for breeding in terms of their expected fertility, while giving birth can help to protect against or at least delay the onset of cervical fibrosis. Alternatively, of course, carrying a foal to term itself carries a risk of serious complica- tions that could compromise future fertility, including cervical tears. On the other hand, using mares exclu- sively as embryo donors over the course of many years, and never allowing them to foal, appears to exacerbate the fibrotic changes to the cervix more commonly associated with the aged maiden mare. The alternative to breeding at a young age is to wait until a mare’s competitive career is over before she becomes a broodmare or embryo donor. Despite never having had a foal, these teenage mares will still be affected by age-related changes that increase the like- lihood that they will be susceptible to PBIE. And, since endometritis is one of themost common reasons for mares failing to establish or maintain pregnancy after breeding,5 anticipating and preventing or treat- ing PBIE is an important aspect of managing older mares in the peri-insemination period.


3. Endometritis and Fertility


Uterine infection and/or inflammation can be detri- mental to fertility in numerous ways. First, if the infection and/or inflammation is pre-existing, the neu- trophils already recruited to the uterus may capture, bind, and phagocytose the spermatozoa soon after they are deposited in the uterus, thereby reducing the likelihood of conception. Second, the persistence of uterine inflammation beyond day 6 after ovulation can interfere with the establishment of pregnancy, ei- ther by a direct toxic effect on the embryo when it enters the uterine lumen or because the inflammation stimulates endometrial PGF2a release leading to pre- mature luteolysis or luteal compromise. In the longer term, persistent or recurrent uterine inflammation may lead to a disturbed uterine environment and accelerate the development of chronic degenerative changes in the endometrium (endometrosis), both of which compromise the ability tomaintain pregnancy.


During the last 20years, it has also become increas- ingly clear that endometritis is not always a result of microbial infection. In fact, it is now accepted that the most common instigator of endometritis is mating or insemination and that a transient uterine inflamma- tion is the normal physiological response to the intra- uterine deposition of semen (thus, breeding-induced endometritis).6 Furthermore, the spermatozoa them- selves appear to be the primary instigator of the inflammatory reaction, which presumably serves to aid the elimination of “excess” spermatozoa that do not make it through the utero-tubal junction and into the oviductal sperm reservoir within the first 4hours after insemination.5 This breeding-induced inflamma- tory reaction consists of two major components: 1) physical clearance of fluid, spermatozoa, contaminat- ing microorganisms, and inflammatory products pro- duced in response to insemination. This mechanical clearance is primarily a result of myometrial contra- ctions that initially help to transport spermatozoa to- ward the oviduct but are subsequently more impo- rtant in eliminating uterine fluid and the other remnants of insemination through the cervix. This physical clearance is further supported bymucociliary action and lymphatic drainage, with the latter becom- ing increasingly important as the cervix tightens and local immunitywanes following ovulation.7 2) The sec- ond arm of the inflammatory response is a cascade of immune system responses that further help to elimi- nate foreign material and restore the uterus to a “clean,” noninflamed state. Since it would not be sen- sible to develop immunological memory to spermato- zoa, much of the immune response is initiated via nonspecific receptors and involves innate pathways including the complement system, proinflammatory cytokines, and neutrophilswhere the latter play a cru- cial role in trapping spermatozoa and bacteria either by direct ligand-receptor binding or by extruding their DNA to formso-called neutrophil extracellular traps.5 The uterine inflammatory response begins within


2hours after insemination and peaks at around 4 to 8hours, both in terms of neutrophil recruitment and proinflammatory cytokine production, after which a combination of mechanical clearance of the stimuli and a shift in the balance of cytokines toward anti- inflammatory mediators should serve to dampen the response and ensure that uterine clearance is com- pleted by 48hours after breeding.6 The mare’sintrin- sic reaction is further modified by various components of seminal plasma, which can augment uterine con- tractility and suppress the inflammatory response, most importantly shortening the duration of the inflammatory reaction. For example, seminal plasma contains prostaglandins that can stimulatemyometrial contractions and factors that inhibit neutrophil trap- ping and phagocytosis of live spermatozoa (CRISP 3) but enhance that of dead spermatozoa (lactoferrin), thereby enhancing the likelihood that live spermatozoa


AAEP PROCEEDINGS / Vol. 68 / 2022 23


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