Impact of early postpartum metritis and systemic antibiotic treatment on the biochemistry and morphology of the bovine uterus at one month postpartum

The study provides new information on the bovine uterus at one month postpartum that applies to bovine and may translate to other species including human. We noted that early postpartum antibiotic treatment did not affect the endpoints that we measured including gene expression and morphology of the uterus. The primary biological driver of uterine function and morphology was inflammation in the uterus at one month postpartum (endometritis; purulent material in the uterine lumen). Inflammation decreased gene expression for growth factor signaling pathways (Wnt, Hippo, and Hedgehog). These three pathways are critical to uterine epithelial cell formation, function, and maintenance. There was also decreased biological processes involved in the formation of ciliated cells in purulent cows. Based on morphology, epithelial cells lost polarity, stretched across open areas of the uterine surface and regained polarity in a process that was like that described for wound closure of other epithelial surfaces including intestine. Wound closure is coordinated by the Wnt PCP pathway. The loss of Wnt signaling in the uterus may explain the slower tissue repair within the luminal epithelium that we observed in cows with endometritis. The decrease in DEG for ciliated cell formation may also be explained by the impact of endometritis on Wnt signaling. Abnormal gland morphology may be explained by failure to establish a ciliated cell population in uterine glands. Future studies and therapeutic solutions should consider uterine involution as a process of wound repair in the face of bacterial infection and address the sequelae of metritis to endometritis by studying factors affecting pathogen load as well as the cow's capacity to regenerate epithelial tissue.