AAEP Reproduction Coverage: Biologic Research in Problem Mares Shows Promise

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Delayed post-breeding clearance of fluid from the mare’s uterus and subsequent inflammation create a “hostile uterine environment for establishing pregnancy,” stated Marco Alvarenga, DVM, MS, PhD, from Sao Paulo State University, Botucatu SP, Brazil. He presented on biologic treatments for endometritis at the 2022 AAEP Convention. 

While numerous therapies are available to treat endometritis, some mares, particularly aged mares, fail to respond. For more than a decade, experts have been looking into biologics to help treat endometritis and improve fertility rates. 

“Is there evidence to support this? I think there is,” Alvarenga said. 

Biologic Treatments for Uterine Inflammation

The key problem with inflammation in the uterus after breeding is an imbalance in cytokine expression. The “problem” mares express more proinflammatory than anti-inflammatory cytokines. 

PRP

Alvarenga said that in Brazil, they use both platelet-rich plasma (PRP) and stem cells for uterine inflammation. However, the clinical results for PRP are particularly interesting. 

He cited an article by Metcalf et al. (2012), which was the first study on PRP for uterine inflammation. It clearly demonstrated that PRP decreased the expression of most inflammatory cytokines, including interleukin (IL)-1B, IL-6 and IL-8. That team then conducted a follow-up study that reported increased pregnancy rates in mares treated with PRP. 

Alvarenga then relayed his own findings from a 2017 study that mares treated with PRP before and after artificial insemination had improved pregnancy rates compared with controls. 

Mares treated with PRP had no bacterial growth after AI compared to the control group, which grew Streptococcus spp. Klebsiella pneumoniae and Escherichia coli.

Newer data presented from Alvarenga showed that intrauterine infusion of PRP in repeat breeder Arabian mares resulted in increased pregnancy rates compared with control horses. What was also interesting was that the research team, Dawod et al. (2021), used lyophilized PRP in addition to fresh PRP. Mares treated with the lyophilized PRP had higher pregnancy rates than the control mares and pregnancy rates similar to those treated with fresh PRP.

Platelet Lysate

Another paper published in 2022 (Colombo et al.) showed that platelet lysate from PRP—which can be kept frozen for future use—also reduces inflammation in the uterus.

“In addition, this study reported a huge decrease in fluid accumulation in mares 24 hours after AI in treated mares,” said Alvarenga. 

Mesenchymal Stem Cell-Conditioned Medium

Alvarenga said that similar to PRP (which can be lyophilized), mesenchymal stem cell-conditioned medium can also be lyophilized to easily store for immediate use. This medium is collected from cultured stem cells that contain more than 200 bioactive molecules to decrease inflammation. Alvarenga further relayed that his research team found a decrease in inflammatory cytokines in mares treated with this product. 

Additional Reading on Biologic Treatments for Endometritis

Additional details regarding the various PRP products described above as well as stem cell conditioned media are available in Alvarenga’s paper included in the AAEP Convention Proceedings. The full Proceedings paper also provided information regarding mesenchymal stem cells and autologous conditioned serum for endometritis. 

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