The objectives of this research plan are to clarify the relationships among endocrine, paracrine, and cellular events during pregnancy which culminate in parturition. It is our expectation that data obtained in pregnant rhesus monkeys and baboons will provide insights into the mechanisms of normal and preterm human labor. Physiological studies in unanesthetized chronically catheterized maternal-fetal preparations in a mobile tether assembly and complementary in vitro studies of intrauterine tissues will be conducted to answer the following questions: (1) How do pituitary and adrenal factors, oxytocin, catecholamines, and environmental cues (e.g., light:dark cycles) regulate circadian patterns in uterine activity? (2) Is progesteron (P4) receptor blockade by RU486 in late gestation associated with the same paracrine (amniotic fluid eicosanoids), structural (gap junctions), and functional (uterine activity) changes seen in spontaneous parturition? (3) Are changes in steroid receptors, their tissue localization or their interaction with DNA related to the onset of labor? (4) Is eicosanoid production by intrauterine tissues altered near term, and if so, by what mechanism (e.g., increased synthesis, decreased inhibition, or redirection of arachidonate metabolism)? Estrone, estradiol, pregnenolone and the sulfate, P4DHEAS, DHEA, androstenedione, cortisol, ACTH, prolactin, oxytocin, prostaglandins (PGE, PGF, PGFM, PGEM-II, 6-keto-PGF 1 alpha), and lipoxygenase metabolites (5, 12, and 15-HETE; leukotriene B4 and C4) will be measured by specific RIA; catecholamines by radioenzymatic assay; steroid receptors by immunocytochemistry, exchange assay and immunoassay; gap junction morphometry by EM; PG production rates in a tissue superfusion system; PG inhibitory and stimulatory substances by bovine seminal vesicles and amnion cell cultures. Results of hormone and tissue assays will be correlated with continuous measurements of fetal heart rate and uterine activity (by amniotic fluid pressure and electromyography). Computer methods will be used for on-line data acquisition and statistical analyses of wave forms, biorhythms and hormonal trends.

Project Start
1979-01-01
Project End
1998-03-31
Budget Start
1995-04-01
Budget End
1996-03-31
Support Year
23
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Oregon Regional Primate Research Center
Department
Type
DUNS #
City
Beaverton
State
OR
Country
United States
Zip Code
97006
Adams Waldorf, K M; Rubens, C E; Gravett, M G (2011) Use of nonhuman primate models to investigate mechanisms of infection-associated preterm birth. BJOG 118:136-44
Grigsby, Peta L; Novy, Miles J; Adams Waldorf, Kristina M et al. (2010) Choriodecidual inflammation: a harbinger of the preterm labor syndrome. Reprod Sci 17:85-94
Bryant-Greenwood, G D; Yamamoto, S Y; Sadowsky, D W et al. (2009) Relaxin stimulates interleukin-6 and interleukin-8 secretion from the extraplacental chorionic cytotrophoblast. Placenta 30:599-606
Novy, Miles J; Duffy, Lynn; Axthelm, Michael K et al. (2009) Ureaplasma parvum or Mycoplasma hominis as sole pathogens cause chorioamnionitis, preterm delivery, and fetal pneumonia in rhesus macaques. Reprod Sci 16:56-70
Adams Waldorf, Kristina M; Persing, David; Novy, Miles J et al. (2008) Pretreatment with toll-like receptor 4 antagonist inhibits lipopolysaccharide-induced preterm uterine contractility, cytokines, and prostaglandins in rhesus monkeys. Reprod Sci 15:121-7
Wilk, J L; Maginnis, G M; Coleman, K et al. (2008) Evaluation of the use of coconut to treat chronic diarrhea in rhesus macaques (Macaca mulatta). J Med Primatol 37:271-6
Wilk, Jennifer; Lewis, Anne; Lukas, Victor (2008) Dermatitis in a rhesus macaque (Macaca mulatta) experimentally infected with simian immunodeficiency virus. J Med Primatol 37 Suppl 1:25-8
Gravett, Michael G; Adams, Kristina M; Sadowsky, Drew W et al. (2007) Immunomodulators plus antibiotics delay preterm delivery after experimental intraamniotic infection in a nonhuman primate model. Am J Obstet Gynecol 197:518.e1-8
Bryant-Greenwood, Gillian D; Kern, Andras; Yamamoto, Sandra Y et al. (2007) Relaxin and the human fetal membranes. Reprod Sci 14:42-5
Witkin, S S; Gravett, M G; Haluska, G J et al. (1994) Induction of interleukin-1 receptor antagonist in rhesus monkeys after intraamniotic infection with group B streptococci or interleukin-1 infusion. Am J Obstet Gynecol 171:1668-72

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