Uterine clinical findings, fertility rate, leucocyte migration, and COX-2 protein levels in the endometrial tissue of susceptible mares treated with platelet-rich plasma before and after AI

Abstract

Persistent mating-induced endometritis (PMIE) results in decreased fertility in horses, thereby causing a significant impact in the horse market. Platelet-rich plasma (PRP), a modulator of the inflammatory response, has been largely used in veterinary medicine. Here, we investigated the effects of PRP on uterine inflammation, conception rate, endometrial polymorphonuclear neutrophil (PMN) migration, and COX-2 protein levels in the endometrial tissue. Thirteen PMIE-susceptible mares were used for artificial insemination (AI). The mares were inseminated with fresh semen in three consecutive cycles in a cross-over study design. The following cycle classifications were used: control cycle, no pharmacological interference; pre-AI, 20 mL of PRP was infused 24 h before AI; and post-AI, 20 mL of PRP was infused four h after AI. Follicular dynamics were monitored daily by transrectal ultrasound. When a follicle larger than 35 mm was detected, ovulation was induced with deslorelin acetate (1 mg, im). AI was performed 24 h after ovulation induction. Intrauterine fluid (FLU) was evaluated by ultrasonography before and 24 h after AI. PMNs in uterine cytology (CYT) and biopsy (HIS) were also observed before and 24 h after AI. Pregnancy was determined within 14 days after ovulation. Number of COX-2 positive cells was evaluated by immunohistochemistry. Both PRP treatments resulted in a decrease of PMNs in the CYT after breeding when compared to controls. FLU did not differ between cycles; however, the conception rates were significantly higher in the PRP mares. Mares positive for endometritis decreased in both treatment groups, and a more intense positive COX-2 labeling was observed in the control group when compared to the two treatment groups. In conclusion, PRP beneficially reduces inflammatory response in PMIE mares independent of when treatments were administered, thus increasing chances of successful pregnancy.

Persistent Breeding-Induced Endometritis in Mares—A Multifaceted Challenge: From Clinical Aspects to Immunopathogenesis and Pathobiology

“…This concurs with another study reporting that PRP decreased endometrial expression of COX-2, decreased PMN numbers in the uterine lumen, and increased pregnancy rates [333]. It has also been shown to act as an anti-inflammatory, and treatment of susceptible mares led to a down-regulation of endometrial IL1β, IL6, and CXCL8 expression [332][333][334][335].…”

“…For the treatment of endometritis in the horse, one study found that PRP administration at the time of breeding decreased the intrauterine inflammatory response in mares suffering from chronic endometritis, although it did not affect NO production [332]. This concurs with another study reporting that PRP decreased endometrial expression of COX-2, decreased PMN numbers in the uterine lumen, and increased pregnancy rates [333]. It has also been shown to act as an anti-inflammatory, and treatment of susceptible mares led to a down-regulation of endometrial IL1β, IL6, and CXCL8 expression [332][333][334][335].…”

Intrauterine administration of platelet‐rich plasma improves embryo implantation by increasing the endometrial thickness in women with repeated implantation failure: A single‐arm self‐controlled trial

“…Moreover, PRP therapy has attracted attention as an effective therapy for RIF. 14,20,21 Future research issues include investigation of the therapeutic effects of PRP on factors not limited to endometrial thickness, and the precise molecular mechanism of the effect of PRP must be elucidated.…”

Non-antibiotic treatment of equine endometritis

“…More recent use of plasma products has been directed towards immunomodulation rather than elimination of pathogens from the uterus. Platelet Rich Plasma (PRP) was shown to modulate the uterine inflammatory response to semen (Reghini et al 2016, Segabinazzi et al 2017, including mRNA down regulation of pro-inflammatory cytokines and NO in one study (Metcalf et al 2012). The downregulation of NO was initially viewed as promising, since an upregulation of NO-synthase and accumulation of NO in uterine fluid in susceptible mares had been proposed as a possible mechanism for impaired uterine contractility in susceptible mares (Alghamdi et al 2005.…”

“…However, subsequent studies could not confirm that PRP caused a consistent downregulation of the gene for NO-synthase or NO (Reghini et al 2016, Troedsson, unpublished observation). Nevertheless, clinical reports have been encouraging, suggesting improved pregnancy rates in mares treated with PRP (Metcalf 2014, Segabinazzi et al 2017. The protocol for treatment with PRP entails separation of 180 mL of whole blood by a special centrifugation system (Angel Cytomedix, Inc.; Gaithersburg, MD), followed by resuspension of the PRP in 10 mL plasma succeeding uterine infusion 24 -36 hours prior to breeding.…”