Persistent breeding-induced endometritis (PBIE) remains a challenging and costly problem in broodmare management. Affecting an estimated 15% of mares, PBIE can derail breeding seasons. Researchers on a recent study are shedding light on how supporting uterine immune function with an oral resveratrol supplement, rather than simply managing fluid accumulation, could change how veterinarians approach these difficult cases.

“Persistent breeding-induced endometritis, or PBIE, is the No. 1 problem in reproductive medicine,” said Carleigh Fedorka, PhD, assistant professor of equine reproductive physiology at Colorado State University, in Fort Collins. “It leads to immense financial and emotional impact, as these mares are bred cycle after cycle without obtaining a pregnancy.”

All mares experience a normal inflammatory response after breeding. In healthy mares, that inflammation resolves within 24 to 48 hours. However, “these diseased mares are unable to clear inflammation in their uterus after breeding,” Fedorka explained. “Their uterus is a fairly hostile place for the embryo to grow and develop. This is the primary reason they are so difficult to get pregnant.”

Studying Uterine Inflammation in Broodmares

Rather than focusing solely on post-breeding uterine fluid—a traditional clinical marker—the researchers evaluated immune cells and signaling proteins that drive inflammation and resolution. While uterine fluid did not change significantly, neutrophils (white blood cells) and cytokines (inflammatory proteins) told a more compelling story.

“Intrauterine fluid is incredibly hard to measure in a research setting as a quantitative variable,” Fedorka said. “We saw significant impacts on other clinical measurements, such as the presence of white blood cells noted on cytology and within low-volume lavage, which is considered the gold-standard diagnostic.”

One of the most notable findings was an early post-breeding increase in interleukin-6 (IL-6) in mares receiving the resveratrol supplement. Although IL-6 is often associated with inflammation, prior research has shown it plays a critical anti-inflammatory and regulatory role in the uterus.

“Diseased mares lack anti-inflammatory signaling, and that deviation is noted at six hours after insemination,” Fedorka said. “IL-6 was one of the proteins that these unhealthy mares lacked, and therefore resveratrol remedying this deficit is very promising.”

Supplementation for Improved Broodmare Uterine Health

Unlike many PBIE therapies, which are invasive and require veterinary administration, the supplement evaluated in this study (Equithrive Mare Pellets) was fed orally. “This is the first product that I am aware of that can be fed orally to mares,” Fedorka said. “It allows owners an inexpensive, noninvasive, and safe option to treat these problem mares. Very few supplements have peer-reviewed data to suggest efficacy. Resveratrol now does.”

Clinical Relevance and Future Research

Next steps will focus on determining whether these immune changes translate into real-world reproductive success. “A clinical trial would be ideal,” Fedorka said. “By showing improvements in embryo recovery or 14-day pregnancy rates, we can better understand just how effective resveratrol is, and we also need to evaluate its safety during pregnancy.”

For veterinarians managing PBIE-susceptible mares, the findings suggest immune modulation (influence) rather than mechanical uterine cleanup alone might be a key piece of the fertility puzzle.