EXPERIMENTAL MODEL FOR CHORIODECIDUAL INFECTION & PRETERM LABOR IN MACAQUES

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Intrauterine infection is an important cause of preterm birth. We have previously demonstrated that experimental intraamniotic infection in rhesus monkeys leads to sequential increases in amniotic fluid (AF) cytokines (TNF and IL-1b) and prostaglandins (PGE2 and PGF2a), followed by preterm labor and delivery. However, the role of choriodecidual infection in preterm labor is unclear. To characterize the pathophysiologic sequence of events following choriodecidual infection, we utilized chronically instrumented rhesus monkeys with timed gestations in which choriodecidual infection was established by inoculation of either a low inoculum (<102 cfu; n=2), moderate inoculum (103-104 cfu; n=4), or high inoculum (>105 cfu; n=3) of Group B streptococcus (GBS) bacteria into the choriodecidual space. Following inoculation, labor occurred in none of 2 low inoculum, 2 of 4 moderate inoculum, and in 2 of 3 high inoculum animals. In the 4 animals with infection-induced labor, increases in uterine contractility occurred 21 hours (14-30 hrs) after inoculation. Increases in uterine contractility were preceded by intraamniotic invasion by the GBS in 3 of 4 animals by an average of 12 hours (6-24 hrs). AF proinflammatory cytokine and prostaglandin concentrations did not rise above pre-inoculation levels among those 5 animals in which inoculation did not result in labor. In contrast, significant increases in AF cytokines and prostaglandins were observed in the 4 laboring animals after, but not before, intraamniotic invasion of GBS Median AF Concentrations (pg/ml) Event TNF IL-1b PGE2 PGF2a Pre-inoculation 50 <20 430 86 Onset Labor 900 110 5,550 316 Delivery 1,320 844 15,754 1,474 These results demonstrate that choriodecidual inoculation may ascend to the amniotic cavity and that following the establishment of intraamniotic infection, preterm labor ensues. In contrast, choriodecidual inoculation without concurrent intraamniotic infection did not lead to preterm labor.