Use of nonhuman primate models to investigate mechanisms of infection-associated preterm birth

Abstract

Preterm birth is the most important direct cause of neonatal mortality and remains a major challenge for obstetrics and global health. Intrauterine infection causes approximately 50% of early preterm births. Animal models using pregnant mice, rabbits or sheep demonstrate the key link between infection and premature birth, but differ in the mechanisms of parturition and placental structure from humans. The nonhuman primate (NHP) is a powerful model which emulates many features of human placentation and parturition. The contributions of the NHP model to preterm birth research are reviewed, emphasising the role of infections and the potential development of preventative and therapeutic strategies.

Figure 1

Jacket-tether system used most recently at the Washington National Primate Research Center, allowing the animal 360° of motion. As the animal turns, the equipment at the top of the cage spins on a swivel to prevent tangling of the catheters. ECG, electrocardiogram; IV, intravenous.

Figure 2

Serial changes after experimental intra-amniotic group B Streptococcus (GBS) inoculation in uterine contractility, GBS [colony-forming units (cfu)/ml], pro-inflammatory cytokines and prostaglandins for single representative animals in each treatment group: (A) control; (B) ampicillin alone; (C) ampicillin, dexamethasone and indomethacin. The x-axis represents the gestational age in days. The y-axis is the hourly contraction area, or the quantity of GBS (cfu/ml; red line), amniotic fluid interleukin-1β (IL-1β; blue line) or prostaglandin E₂ (PGE₂; green line). The length of time that a particular drug was administered is indicated above (B) and (C). Reprinted from the American Journal of Obstetrics and Gynaecology, with permission of Elsevier, and modified.

Figure 3

Temporal relationships between lipopolysaccharide (LPS) inoculation, uterine activity, and amniotic fluid cytokines and prostaglandins in representative animals from each experimental group receiving LPS only (A) and intra-amniotic Toll-like receptor 4 antagonist (TLR4A; green arrowhead) 1 hour prior to intra-amniotic LPS (B). The x-axis represents the gestational age in days, ranging from vascular implantation surgery until caesarean delivery. The y-axis is the hourly contraction area, or the level of amniotic fluid tumour necrosis factor-α (TNF-α; orange line) or prostaglandin E₂ (PGE₂; blue line). Reprinted with permission. 2007 American Chemical Society.