Impact of metritis and systemic antibiotic treatment on the biology and morphology of the bovine uterus at one month postpartum†.

The biology and morphology of the uterus were explored at approximately one month postpartum for cows that were diagnosed with metritis (uterine disease; n = 18) or healthy (n = 17) at 7-10 days postpartum and either treated or untreated with ceftiofur hydrochloride (2 × 2 factorial). Cows were slaughtered at one month postpartum, and the uterine horns were flushed to identify cows with a purulent or clear (non-purulent) content. RNA was isolated from caruncular and inter-caruncular endometria for RNA sequencing. Light microscopy was used to quantify inflammation, and scanning electron microscopy was used to assess the closure of the luminal surface of the uterus and the morphology of uterine glands. Results were that postpartum antibiotic treatment did not affect the endpoints that were measured including gene expression and morphology of the uterus. The primary biological driver of uterine function and morphology was inflammation at one month postpartum (endometritis; purulent material in the uterine lumen). Inflammation decreased epithelial growth factor signaling pathway expression (Wnt, Hippo, and Hedgehog) and biological processes involved in the formation of ciliated cells. Based on morphology, epithelial cells closed open areas of a denuded uterine surface using a process that involved depolarization and cell movement (planar cell polarity). Non-canonical Wnt signaling drives planar cell polarity, and the loss of Wnt signaling may explain the slower tissue repair in cows with endometritis. Future studies and therapeutic treatments should consider uterine involution as a process of wound repair and tissue regeneration in the face of bacterial infection.