Funding outcome

In the transformation of the uterus from pregnancy to parturition, circulating leukocytes are stimulated via chemoattractant to invade the uterus to contribute to the transformation process; this occurs in every birth. As parturition approaches, higher levels of leukocytes invade the uterus in response to chemoattractant coming from the human fetal membranes. We have developed a migration assay that utilizes this concept of increasing responsiveness of these cells in order to predict the timing of delivery. The largest variety of leukocytes migrating in our assay are neutrophils which correlates with studies demonstrating that neutrophils are present in the greatest number in the uterus at term and that this number increases with the onset of labour. The possibility exists that increasing responsiveness of the leukocytes may be due to an upregulation of receptors for chemoattractant, better coupling mechanisms leading to intracellular signal transduction, or more efficient cellular mechanisms of migration. Since it is well established that prostaglandin and interleukin-1 receptors on uterine myometrium change with labour onset, the most likely and attractive possibility is an increased responsiveness due to elevated receptors on the neutrophils. We therefore hypothesized that elevated leukocyte receptors to chemoattractants mediate the increased invasion of the uterus by leukocytes before delivery at term or preterm. Objective: The proposed study aims to (1) identify expression patterns in leukocyte (neutrophil) receptors in women and mice in late pregnancy and (2) to study the effects of cytokines and chemoattactant upon the expression of these receptors in human neutrophils.