A Novel Tissue Explant Culture Model For Testing of Candidate Treatments for Inflammation of the Uterus in Pigs.

Abstract Background: Endometritis is an inflammatory condition of the uterus leading to complications with reproductive organs, miscarriage and infertility. The first-line treatment of endometritis in pigs are antibiotics, which do not always resolve inflammation and contribute to antibiotic resistance. There is an urgent need for the development of alternative treatments for endometritis. Here we propose and validate the first porcine tissue explant model for uterine inflammation and test naturally derived compounds for their effectiveness as anti-inflammatory therapies in porcine endometrial tissue. Methods: Uterine endometrial explants were harvested from uteri of sows sent to slaughter. Tissue biopsies were collected at follicular and luteal phases of the oestrous cycle. Biopsies were washed and these tissue ‘explants’ were cultured. Explants were treated at 24 hr with oxytocin (to stimulate PGF 2αproduction) or LPS (to mimic infection and induce inflammation. Explants were retained for RT-PCR analysis. Supernatants were harvested and concentrations of markers were measured by ELISA and Luminex. Results: The data generated thus far show a dose dependent response of IL-6 secretion to LPS stimulation, which demonstrates the validity of our model. Inflammation can be stimulated in an in vitrosetting to mimic porcine endometritis and we present data to show the change in cytokine levels in response to treatment with naturally derived compounds. Conclusions: This data shows that inflammation can be stimulated in an in vitrosetting to mimic porcine endometritis This model is a tool for testing of novel compounds and their potential anti-inflammatory effects on the porcine endometrium. Supported by an Innovate UK Grant (Project Reference: 98015) (https://gtr.ukri.org/projects?ref=98015)