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Chapter 20 : Simian Model for Infection-Associated Preterm Labor
Authors:
Michael G. Gravett1,
Miles J. Novy2
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Affiliations:
1: Division of Reproductive Sciences, Oregon Regional Primate Research Center, and Departments of Obstetrics and Gynecology, Legacy Emanuel Hospital and Health Center, and Oregon Health Sciences University, Beaverton and Portland, OR 97227;
2: Division of Reproductive Sciences, Oregon Regional Primate Research Center, and Department of Obstetrics and Gynecology, Oregon Health Sciences University, Beaverton and Portland, OR 97227
Content Type: Monograph
Publication Year:
1999
Category: Bacterial Pathogenesis; General Interest
Book DOI:
10.1128/9781555818210
Chapter DOI:
10.1128/9781555818210.ch20
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Abstract:
Preterm labor that results in premature birth is the most common cause of perinatal mortality, accounting for 80% of perinatal deaths which are not attributable to congenital malformations. There is now considerable evidence to suggest that cytokines participate in the pathogenesis of infection-associated preterm labor. To examine the temporal and quantitative relationships between intra-amniotic infection and preterm labor, the authors developed a simian model involving chronically catheterized rhesus monkeys (Macaca mulatta) with timed gestations. Bacterial vaginosis, previously associated with preterm labor and intra-amniotic infection in women, was identified by Gram stain criteria in 8 of 31 monkeys (26%), a prevalence similar to that reported in women, and was likewise associated with increased intravaginal concentrations of Gardnerella vaginalis, Mobiluncus spp., and anaerobes. Following intra-amniotic infection, increases in prostaglandin E2 (PGE2) and PGF2α concentrations in amniotic fluid occur in parallel with increases in cytokine concentrations in amniotic fluid and precede increases in uterine contractility. The presence of a single fetus, the hormonal control of parturition, and hemochorial placentation with an abundant amniotic fluid cavity all approximate the human situation. Ideally, prevention of prematurity should be directed toward identification and eradication of the offending microorganism while it is still confined to the lower genital tract, as has been demonstrated for certain lower genital tract infections.
Citation:
Gravett M, Novy M.
1999.
Simian Model for Infection-Associated Preterm Labor,
p 329-352.
In
Hitchcock P, MacKay H, Wasserheit J, Binder R (ed),
Sexually Transmitted Diseases and Adverse Outcomes of Pregnancy.
ASM Press, Washington, DC.
doi: 10.1128/9781555818210.ch20
Figures
Simian Model for Infection-Associated Preterm Labor
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Citation:
Gravett M, Novy M.
1999.
Simian Model for Infection-Associated Preterm Labor,
p 329-352.
In
Hitchcock P, MacKay H, Wasserheit J, Binder R (ed),
Sexually Transmitted Diseases and Adverse Outcomes of Pregnancy.
ASM Press, Washington, DC.
doi: 10.1128/9781555818210.ch20
/content/10.1128/9781555818210.chap20.fig20-1
Figure 1
Diagrammatic representation of the chronic jacket-and-tether system utilized to study intrauterine infection in the rhesus macaque.
10.1128/9781555818210/fig20-1_thmb.gif
10.1128/9781555818210/fig20-1.gif
Figure 1
Diagrammatic representation of the chronic jacket-and-tether system utilized to study intrauterine infection in the rhesus macaque.
Citation:
Gravett M, Novy M.
1999.
Simian Model for Infection-Associated Preterm Labor,
p 329-352.
In
Hitchcock P, MacKay H, Wasserheit J, Binder R (ed),
Sexually Transmitted Diseases and Adverse Outcomes of Pregnancy.
ASM Press, Washington, DC.
doi: 10.1128/9781555818210.ch20
/content/10.1128/9781555818210.chap20.fig20-2
Figure 2
Temporal relationship between intra-amniotic infection, cytokine and prostaglandin concentrations in amniotic fluid, and uterine activity for a single representative monkey. The clinical onset of labor is denoted by an arrow and L. Reproduced from Gravett et al. (1994a) with permission of the publisher. (A) Quantitative relationship between group B streptococcus (GBS) concentrations in amniotic fluid and uterine contractility, expressed as the HCA under the amniotic fluid-pressure curve. (B) Concentrations of IL-1β, TNF, and IL-6 in amniotic fluid before and after infection. (C) Concentrations of PGE2 and PGF2α in amniotic fluid before and after infection.
10.1128/9781555818210/fig20-2_thmb.gif
10.1128/9781555818210/fig20-2.gif
Figure 2
Temporal relationship between intra-amniotic infection, cytokine and prostaglandin concentrations in amniotic fluid, and uterine activity for a single representative monkey. The clinical onset of labor is denoted by an arrow and L. Reproduced from Gravett et al. (1994a) with permission of the publisher. (A) Quantitative relationship between group B streptococcus (GBS) concentrations in amniotic fluid and uterine contractility, expressed as the HCA under the amniotic fluid-pressure curve. (B) Concentrations of IL-1β, TNF, and IL-6 in amniotic fluid before and after infection. (C) Concentrations of PGE2 and PGF2α in amniotic fluid before and after infection.
Citation:
Gravett M, Novy M.
1999.
Simian Model for Infection-Associated Preterm Labor,
p 329-352.
In
Hitchcock P, MacKay H, Wasserheit J, Binder R (ed),
Sexually Transmitted Diseases and Adverse Outcomes of Pregnancy.
ASM Press, Washington, DC.
doi: 10.1128/9781555818210.ch20
/content/10.1128/9781555818210.chap20.fig20-3
Figure 3
Prostaglandin concentrations in amniotic fluid for spontaneous (n = 4) and infection-induced parturition (n = 4). Data are expressed as mean and standard deviation. Concentrations observed among animals with infection-induced labor were greater than those with spontaneous labor for both PGE2 (17,851 ± 4,548 and 2,765 + 782 pg/ml, respectively; P < 0.05) and for PGF2α (6,431 ± 4,026 and 708 ± 89 pg/ml, respectively; P < 0.05). Comparisons were made by the Mann-Whitney U test. Reproduced from Gravett et al. (1994b) with permission of the publisher.
10.1128/9781555818210/fig20-3_thmb.gif
10.1128/9781555818210/fig20-3.gif
Figure 3
Prostaglandin concentrations in amniotic fluid for spontaneous (n = 4) and infection-induced parturition (n = 4). Data are expressed as mean and standard deviation. Concentrations observed among animals with infection-induced labor were greater than those with spontaneous labor for both PGE2 (17,851 ± 4,548 and 2,765 + 782 pg/ml, respectively; P < 0.05) and for PGF2α (6,431 ± 4,026 and 708 ± 89 pg/ml, respectively; P < 0.05). Comparisons were made by the Mann-Whitney U test. Reproduced from Gravett et al. (1994b) with permission of the publisher.
Citation:
Gravett M, Novy M.
1999.
Simian Model for Infection-Associated Preterm Labor,
p 329-352.
In
Hitchcock P, MacKay H, Wasserheit J, Binder R (ed),
Sexually Transmitted Diseases and Adverse Outcomes of Pregnancy.
ASM Press, Washington, DC.
doi: 10.1128/9781555818210.ch20
/content/10.1128/9781555818210.chap20.fig20-4
Figure 4
Concentrations of IL-1β (A), TNF (B), and PGE2 and PGF2α (C) in amniotic fluid and uterine activity (D) after serial intra-amniotic infusions of 2, 5, 10, or 20 μg of recombinant human IL-1α in four catheterized uninfected animals. Uterine activity is expressed as the HCA under the amniotic fluid-pressure curve. Reproduced from Baggia et al. (1996) with permission of the publisher.
10.1128/9781555818210/fig20-4_thmb.gif
10.1128/9781555818210/fig20-4.gif
Figure 4
Concentrations of IL-1β (A), TNF (B), and PGE2 and PGF2α (C) in amniotic fluid and uterine activity (D) after serial intra-amniotic infusions of 2, 5, 10, or 20 μg of recombinant human IL-1α in four catheterized uninfected animals. Uterine activity is expressed as the HCA under the amniotic fluid-pressure curve. Reproduced from Baggia et al. (1996) with permission of the publisher.
Citation:
Gravett M, Novy M.
1999.
Simian Model for Infection-Associated Preterm Labor,
p 329-352.
In
Hitchcock P, MacKay H, Wasserheit J, Binder R (ed),
Sexually Transmitted Diseases and Adverse Outcomes of Pregnancy.
ASM Press, Washington, DC.
doi: 10.1128/9781555818210.ch20
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Tables
Simian Model for Infection-Associated Preterm Labor
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Citation:
Gravett M, Novy M.
1999.
Simian Model for Infection-Associated Preterm Labor,
p 329-352.
In
Hitchcock P, MacKay H, Wasserheit J, Binder R (ed),
Sexually Transmitted Diseases and Adverse Outcomes of Pregnancy.
ASM Press, Washington, DC.
doi: 10.1128/9781555818210.ch20
/content/10.1128/9781555818210.chap20.tab20-1
Table 1
Advantages and disadvantages of a nonhuman primate model for preterm delivery and intrauterine infection a
Table 1
Advantages and disadvantages of a nonhuman primate model for preterm delivery and intrauterine infection a
Citation:
Gravett M, Novy M.
1999.
Simian Model for Infection-Associated Preterm Labor,
p 329-352.
In
Hitchcock P, MacKay H, Wasserheit J, Binder R (ed),
Sexually Transmitted Diseases and Adverse Outcomes of Pregnancy.
ASM Press, Washington, DC.
doi: 10.1128/9781555818210.ch20
/content/10.1128/9781555818210.chap20.tab20-2
Table 2
Cervicovaginal microbial flora among 31 pregnant rhesus macaques at the Oregon Regional Primate Research Center
Table 2
Cervicovaginal microbial flora among 31 pregnant rhesus macaques at the Oregon Regional Primate Research Center
Citation:
Gravett M, Novy M.
1999.
Simian Model for Infection-Associated Preterm Labor,
p 329-352.
In
Hitchcock P, MacKay H, Wasserheit J, Binder R (ed),
Sexually Transmitted Diseases and Adverse Outcomes of Pregnancy.
ASM Press, Washington, DC.
doi: 10.1128/9781555818210.ch20
/content/10.1128/9781555818210.chap20.tab20-3
Table 3
Summary of bacterial counts and cytokine and prostaglandin concentrations in amniotic fluid and uterine activity in experimental intra-amniotic infection
Table 3
Summary of bacterial counts and cytokine and prostaglandin concentrations in amniotic fluid and uterine activity in experimental intra-amniotic infection
Citation:
Gravett M, Novy M.
1999.
Simian Model for Infection-Associated Preterm Labor,
p 329-352.
In
Hitchcock P, MacKay H, Wasserheit J, Binder R (ed),
Sexually Transmitted Diseases and Adverse Outcomes of Pregnancy.
ASM Press, Washington, DC.
doi: 10.1128/9781555818210.ch20
/content/10.1128/9781555818210.chap20.tab20-4
Table 4
Mean IL-1β and prostaglandin concentrations in amniotic fluid and uterine activity following intra-amniotic IL-1β infusion with and without indomethacin pretreatment a
Table 4
Mean IL-1β and prostaglandin concentrations in amniotic fluid and uterine activity following intra-amniotic IL-1β infusion with and without indomethacin pretreatment a
Citation:
Gravett M, Novy M.
1999.
Simian Model for Infection-Associated Preterm Labor,
p 329-352.
In
Hitchcock P, MacKay H, Wasserheit J, Binder R (ed),
Sexually Transmitted Diseases and Adverse Outcomes of Pregnancy.
ASM Press, Washington, DC.
doi: 10.1128/9781555818210.ch20
/content/10.1128/9781555818210.chap20.tab20-5
Table 5
Median concentrations of IL-1β and IL-1ra in amniotic fluid and uterine activity following experimental intra-amniotic infection a
Table 5
Median concentrations of IL-1β and IL-1ra in amniotic fluid and uterine activity following experimental intra-amniotic infection a
Citation:
Gravett M, Novy M.
1999.
Simian Model for Infection-Associated Preterm Labor,
p 329-352.
In
Hitchcock P, MacKay H, Wasserheit J, Binder R (ed),
Sexually Transmitted Diseases and Adverse Outcomes of Pregnancy.
ASM Press, Washington, DC.
doi: 10.1128/9781555818210.ch20
/content/10.1128/9781555818210.chap20.tab20-6
Table 6
Median steroid hormone concentrations in rhesus monkeys (n = 4) undergoing spontaneous parturition near term a
Table 6
Median steroid hormone concentrations in rhesus monkeys (n = 4) undergoing spontaneous parturition near term a
Citation:
Gravett M, Novy M.
1999.
Simian Model for Infection-Associated Preterm Labor,
p 329-352.
In
Hitchcock P, MacKay H, Wasserheit J, Binder R (ed),
Sexually Transmitted Diseases and Adverse Outcomes of Pregnancy.
ASM Press, Washington, DC.
doi: 10.1128/9781555818210.ch20
/content/10.1128/9781555818210.chap20.tab20-7
Table 7
Median steroid hormone concentrations in rhesus monkeys (n near terma
Table 7
Median steroid hormone concentrations in rhesus monkeys (n near terma
Citation:
Gravett M, Novy M.
1999.
Simian Model for Infection-Associated Preterm Labor,
p 329-352.
In
Hitchcock P, MacKay H, Wasserheit J, Binder R (ed),
Sexually Transmitted Diseases and Adverse Outcomes of Pregnancy.
ASM Press, Washington, DC.
doi: 10.1128/9781555818210.ch20