Birth in our Canadian society is a daily phenomenon that occurs approximately 1,100 times per day, but unfortunately not always within the normal time frame, after 39-40 weeks of pregnancy. The present thesis addresses the question: What factors initiate premature labour? / Although the process is incompletely understood, it is known that immune and endocrine factors as well as the fetus itself contribute to the initiatory signals that bring about parturition. Indeed, cytokines, oxytocin, and steroids have been shown to affect the tone, amplitude and frequency of myometrial contractions. Given that their effects can be abolished by the addition of cyclooxygenase (Cox) inhibitors, the changes, in vivo, of Cox-1 and Cox-2 gene expression during pregnancy and the effects of cytokines and oxytocin on prostaglandin synthesis were examined. / Analysis by Polymerase Chain Reaction and Northern blotting indicated that uterine Cox-2 transcript levels increased approaching delivery and that the Cox-1 mRNA levels remained relatively unchanged throughout pregnancy. Immunohistochemical staining for the Cox-2 and OTR proteins revealed both to be co-expressed in the myometrium and in endometrial epithelial cells. Within the stroma, no OTR staining was found but intense staining for Cox-2 was noticed during labour. / Following the in vivo work, the effects of cytokines and oxytocin on various cell lines were tested. When IL-1$ beta$ and TNF-$ alpha$ were added to CUS-V2, a stromal cell line I developed, an increase in Cox-2 mRNA levels and an approximately 2 fold increase in PgF$ sb{2 alpha}$ released per 24 hours was observed. Under the same conditions, no changes in the levels of Cox-1 or GAPDH mRNA were observed. The effect of oxytocin was more pronounced. Its addition to CHO cells expressing constitutively the rat oxytocin receptor led to a 107 fold increase in the amount of PgE$ sb2$ released in a 24 hour period and a increase in Cox-2 protein levels as determined by Western blot analysis. Therefore, since uterine oxytocin and oxytocin receptor, in the rat, are regulated by estrogen and progesterone, and these steroids are in turn regulated by placental born factors, a clearer understanding is emerging of their interaction. These three systems might synergistically or additively interact to produce an amplified signal that initiates strong synchronous contractions and a delayed, but a parallel, increase in cervical compliance by inducing prostaglandins.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.41968 |
| Date | January 1997 |
| Creators | Arslan, Ali. |
| Contributors | Zingg, H. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001558688, proquestno: NQ29877, Theses scanned by UMI/ProQuest. |
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