• Myatt, Leslie (PI)
  • Larsen, William (PI)
  • Everson, William (PI)
  • Larson, William (PI)
  • Sperelakis, Nicholas (PI)
  • Siddiqi, Tariq (PI)

Project: Research project

Project Details


Preterm labor is the major cause of perinatal morbidity and mortality and
imposes huge financial and emotional burdens upon society. Currently, no
treatment exists that significantly reduces morbidity and mortality
resulting from preterm labor. Our lack of knowledge of the myometrial
events surrounding preterm labor is not surprising given how little we know
of the mechanisms controlling normal parturition. Therefore, the central
theme of this program is to increase our understanding of the cellular
mechanisms that regulate myometrial activity. Four closely-related basic
science projects have been assembled and are supported by three core units.
These projects will utilize common human and rat tissues and hormonally
manipulated rat models of preterm labor. The objectives of the four
projects are to determine:
(1) The ontogeny of synthesis, transport, endocytosis and degradation of
gap junction protein, connexin 43 and the influence of hormonal and
pharmacologic manipulation on connexin 43 turnover in myometrium;
(2) The ontogeny, quantitation and physiological function of fast sodium
channels and the accompanying fast sodium current in myometrium with regard
to signal propagation and automaticity and the relationship to
sodium/calcium exchange and hence intracellular ionized calcium;
(3) The expression, localization, and hormonal regulation of annexins II
and VI in myometrium, the role of annexin II in connexin 43 expression and
activity and the role of annexin VI in calcium release from the
sarcoplasmic reticulum, on the IP3 sensitive calcium channel and on calcium
dynamics oligonucleotides antisense to annexin mRNA will be employed in
these studies;
(4) The mechanisms whereby steroid hormones acting via receptor or
membrane-mediated events determine eicosanoid synthesis and action in
myometrium in term or preterm labor or following hormonal manipulation. An administrative core serves to allow successful implementation and
administration of the program. A clinical core serves to provide human
myometrium and blood obtained at term or preterm from patients who are or
are not in labor to the four projects in addition to maintaining the
requisite patient information. A tissue culture core serves to collect and
distribute tissue and provide cultured rat and human myometrial cells to
the four projects. Overall, these studies will increase our knowledge of the mechanisms
controlling parturition and the comparative changes in preterm labor.
Effective start/end date3/1/922/28/98


  • National Institutes of Health: $619,812.00
  • National Institutes of Health: $643,443.00
  • National Institutes of Health: $76,500.00
  • National Institutes of Health: $659,266.00


  • Medicine(all)


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