Resveratrol supplementation improves uterine immune resolution in mares susceptible to persistent breeding-induced endometritis.

Abstract

INTRODUCTION: Persistent breeding-induced endometritis (PBIE) remains a major problem in equine reproduction. This disorder is characterized by prolonged post-breeding inflammation and is associated with advanced age, reduced endometrial quality, and impaired uterine immune function. Resveratrol, a polyphenolic compound with documented anti-inflammatory activity in humans, has not been investigated for its ability to modulate uterine inflammation in mares. We hypothesized that resveratrol supplementation would attenuate the exaggerated inflammatory response characteristic of PBIE-susceptible mares. METHODS: Six susceptible mares completed a control cycle followed by 21.8 ± 0.8 days of oral resveratrol treatment (2,800 g SID). During both cycles, mares were inseminated with 500 × 106 freezekilled spermatozoa and evaluated at 6 and 24 h post-breeding. Uterine fluid was quantified via transrectal ultrasonography, and neutrophil counts were assessed using cytobrush and low-volume lavage (LVL). Luminal cytokines were measured with an equine multiplex immunoassay. Data were analyzed using a general linear model in SAS 9.4® (≤ 0.05). RESULTS: Resveratrol supplementation did not alter uterine fluid accumulation (= 0.35) but reduced neutrophilia in LVL samples at 6 h (= 0.09) and 24 h (= 0.03), as well as in cytobrush samples at 24 h (= 0.04). Cytokine profiling revealed a trend toward decreased IL-1β at 6 h (= 0.06) with a concurrent increase in IL-6 (= 0.04) and a trend toward reduced IL-8 at 24 h (= 0.09). DISCUSSION: These findings demonstrate that resveratrol modulates specific components of the uterine inflammatory response in PBIE-susceptible mares. Such immunomodulatory effects may have relevance for improving reproductive efficiency, warranting further mechanistic and clinical investigation.