The objectives of this research plan are to clarify the relationships among endocrine and vascular 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 mechanism of human labor (normal and premature) and placental hormone production. Major emphasis will be placed on physiological studies in unanesthetized chronic fetal preparations and on complementary in vitro studies of fetal and placental tissues to answer the following questions: (1) How do fetal and maternal adrenal steroids, prostaglandins (PGs), oxytocin, catecholamines and calcium antagonists interact with environmental cues (e.g., light:dark cycles) in regulating circadian patterns in uterine activity? (2) Are prostaglandins temporally or causally related to the initiation of parturition and by what mechanism? (3) Is there evidence for local """"""""progesterone withdrawal"""""""" in the primate uterus prior to the onset of labor? (4) What is the role of sex-steroid-binding protein (SBP) and corticosteroid binding globulin (CBG) in regulating free and bound steroid concentrations in maternal and fetal plasma and amniotic fluid? (5) How is fetoplacental steroidogenesis regulated by tropic factors, enzyme availability, precursor supply and/or placental blood flow? Estrone, estradiol, pregnenolone (P5), P5 sulfate, progesterone, DHEAS, DHEA, androstenedione, testosterone, ACTH, prolactin, oxytocin and prostaglandins (PGE, PGF, PGFM, PGEM-II, 6-keto-PGFl Alpha) will be measured by specific RIA's; cortisol by HPLC and RIA; catecholamines by radioenzymatic assays; SBP and CBG by filtered disk assay and immunoassay. Total and free (unbound) concentrations of steroid hormones will be compared in maternal, fetal and newborn blood and amniotic fluid. Metabolic clearance rates, and transfer rates of placental hormones and PGs will be determined in vivo by steady state infusions of isotopically-labeled hormones and in vitro by tissue superfusion techniques. Blood flow will be measured by electromagnetic flow-meter and radioactive microspheres and 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 for statistical analyses of wave forms, biorhythms, and hormonal time-trends.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD006159-15
Application #
3310453
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1979-01-01
Project End
1988-06-30
Budget Start
1987-01-01
Budget End
1988-06-30
Support Year
15
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Oregon Regional Primate Research Center
Department
Type
DUNS #
City
Beaverton
State
OR
Country
United States
Zip Code
97006
Acosta, Edward P; Grigsby, Peta L; Larson, Kajal B et al. (2014) Transplacental transfer of Azithromycin and its use for eradicating intra-amniotic ureaplasma infection in a primate model. J Infect Dis 209:898-904
Grigsby, Peta L; Novy, Miles J; Sadowsky, Drew W et al. (2012) Maternal azithromycin therapy for Ureaplasma intraamniotic infection delays preterm delivery and reduces fetal lung injury in a primate model. Am J Obstet Gynecol 207:475.e1-475.e14
Knutson, Jayme S; Harley, Mary Y; Hisel, Terri Z et al. (2012) Contralaterally controlled functional electrical stimulation for stroke rehabilitation. Conf Proc IEEE Eng Med Biol Soc 2012:314-7
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
Waites, Ken B; Schelonka, Robert L; Xiao, Li et al. (2009) Congenital and opportunistic infections: Ureaplasma species and Mycoplasma hominis. Semin Fetal Neonatal Med 14:190-9
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

Showing the most recent 10 out of 38 publications