Abstract

The objectives of this research plan are to clarify the relationships among endocrine, paracrine, and cellular events which culminate in parturition in primates.
Aim 1 will establish the separate effects of exogenous ACTH or CRH administered to the fetus or mother at 80+ percent gestation in terms of inducing premature labor as well as describe the changes in the endogenous levels of the same hormones.
Aim 2 will describe the presence of androgen and glucocorticoid receptors (ARs, GRs) in rhesus amnion, chorion, decidua, and myometrium at 80 and 100 percent of gestation using immunohistochemistry and ribonuclease protection assay of receptor mRNA. A second part of Aim 2 will use maternal/fetal infusion of androgen agonists and antagonists and a 5-alpha reductase inhibitor to determine the effects of alterations of maternal/fetal androgen levels on gestational length.
Aim 3 examines possible mechanisms of progesterone withdrawal by testing for a switch between myometrial progesterone receptor (PR) subtypes (A&B) near term, or a non-genomic mechanism of reduced amniochorion calcium mobilization (""""""""membrane effects"""""""") in immune cells.
Aim 4 will determine the effects of intraamniotic administration of human IL-8 on parturition.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD006159-30
Application #
6520669
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Ilekis, John V
Project Start
1979-01-01
Project End
2005-03-31
Budget Start
2002-04-01
Budget End
2005-03-31
Support Year
30
Fiscal Year
2002
Total Cost
$428,685
Indirect Cost

  Institution

Name
Oregon Health and Science University
Department
Type
Other Domestic Higher Education
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239

  Publications

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
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
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
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

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