Ultrasound-Guided Intrauterine Injection of Lipopolysaccharide as a Novel Model of Preterm Birth in the Mouse

Abstract

Mouse models are used to study mechanisms that link intrauterine infection and preterm birth (PTB). To mimic intrauterine infection, lipopolysaccharide (LPS) is commonly injected into the uterus via minilaparotomy, which is invasive, and can cause PTB in control animals. We hypothesized that less-invasive ultrasound-guided intrauterine LPS injection or intravaginal LPS administration could induce PTB by stimulating an inflammatory response of the uteroplacental tissues, while minimizing PTB in control animals. On day 17 of gestation mice received LPS intravaginally (10 to 240 μg; n = 3 to 8) or into the uterus (20 μg) under ultrasound guidance (n = 7) or via laparotomy (n = 7). Control animals received phosphate-buffered saline (PBS; n = 5 to 7). Intrauterine administration of LPS, both under ultrasound guidance and via laparotomy, induced delivery earlier than in PBS control groups (P < 0.01). Intravaginal LPS administration did not stimulate PTB. Quantitative real-time PCR and immunohistochemistry of tissues harvested 6 hours after treatment confirmed that ultrasound-guided LPS administration induced a localized inflammatory response. Ultrasound-guided intrauterine LPS injection reliably induces PTB in the mouse and mimics the local inflammatory and immune responses observed in the more-invasive laparotomy model of inflammation-induced PTB. Ultrasound-guided intrauterine LPS injection is a useful novel model of PTB for future studies and concords with the principles of reduction, replacement, and refinement.