Researchers probe immune response in the wombs of in-season mares

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foalResearchers have used genetic sequencing to learn more about the immune response in the womb in horses when in season.

In doing so, the University of Melbourne study team cast fresh light on endometritis – an infection of the lining of the inner womb – which can affect reproduction of mares.

Equine endometritis is a local inflammation of the superficial layers of the uterus. It has been ranked as the third most common medical problem of adult horses by equine practitioners in the United States, with about 15 percent of all thoroughbred mares showing signs of persistent mating-induced endometritis.

The decrease in pregnancy rates in affected mares causes significant losses to horse breeding industries, the authors said.

Transient endometritis is the physiological response to the arrival in the womb of sperm, seminal plasma, cell debris and bacteria during natural breeding or artificial insemination. This, they said, had also been described in other mammals, including dogs.

Healthy mares are able to clear the contamination of their uterus within six hours after breeding.

In contrast, mares susceptible to persistent mating-induced endometritis show a prolonged inflammatory response lasting up to 96 hours after breeding, and bacterial uterine infections were found in 25-60% of barren mares.

The two most commonly isolated organisms, Escherichia coli (E. coli) and Streptococcus equi subspecies zooepidemicus (Sc. zooepidemicus) are both considered opportunistic pathogens, suggesting that the phenomenon may be more related to host factors than the virulence of the bacteria.

Similar conditions, they said, can be seen in the genital tract of other species, including cattle, sows, bitches and humans, when increased numbers of bacteria meet a weak immune system.

Bacterial growth, inflammatory cell migration and clinical illness seemed to be correlated with high progesterone concentrations, while oestrus conditions significantly reduced the incidence of persistent infection and inflammation in the uterus.

Christina Marth and her colleagues, writing in the journal BMC Genomics, said the steroid hormone environment in healthy horses seemed to have a significant impact on the efficiency of their uterine immune response.

They set out to characterize the changes in gene expression in the equine endometrium – the mucous membrane that lines the inside of the womb – in response to the introduction of bacterial pathogens and the influence of steroid hormone concentrations on this expression.

They analyzed endometrial biopsies collected from five 3-4-year-old standardbred horses both before and 3 hours after the introduction of Escherichia coli once in season, and then five days after ovulation.

Comparison between time points revealed that 2422 genes were expressed at significantly higher levels and 2191 genes at significantly lower levels three hours after the introduction of the pathogens in oestrus in comparison to pre-inoculation levels.

Five days after coming into season, the expression of 1476 genes was up-regulated and 383 genes were down-regulated after the introduction of the pathogens.

The researchers noted that E. coli was the bacteria most commonly isolated from mares with fertility problems. The bacterium had a generation time of around 20 minutes, highlighting the need for a rapid immune response to contain the infection. However, an excessive or prolonged inflammatory response will damage tissue integrity and, in the uterus, also interfere with successful pregnancy.

“The results of this study emphasize the complexity of an effective uterine immune response during acute endometritis and the tight balance between pro- and anti-inflammatory factors required for efficient elimination of bacteria,” they reported.

“However, while we have identified a large number of genes of potential interest, future studies will need to examine protein expression.”

They said their work was one of the first high-throughput genetic analyses of the uterine inflammatory response in any species and several new potential targets for treatment of inflammatory diseases of the equine uterus had been identified.

Overall, their data suggested that antimicrobial peptides may have received less attention than they deserved as potential treatment targets for equine endometritis.

Marth was joined in the research by Neil Young, Lisa Glenton, Glenn Browning and Natali Krekeler, all from the University of Melbourne; and Drew Noden, from Cornell University in New York.

Deep sequencing of the uterine immune response to bacteria during the equine oestrous cycle
Christina D. Marth, Neil D. Young, Lisa Y. Glenton, Drew M. Noden, Glenn F. Browning and Natali Krekeler
BMC Genomics 2015 16:934 DOI: 10.1186/s12864-015-2139-3

The full study can be read here

The original research was published under a Creative Commons License

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