In the human uterus prostaglandins (PG) PGE2, PGD2, PGI2, PGF2¿ and
Thromboxane A2 (TXA2), also termed prostanoids, are synthesised and deactivated
to 15-keto PGE2, J2 metabolites, 6-keto-PGF1¿, 15-keto PGF2¿ and TXB2
respectively. However, not all metabolites have been analysed simultaneously
within the same tissue. The primary objective of this thesis was to determine full
uterine prostanoid profiles in human non-pregnancy, pregnancy and parturition, to
better understand these processes and find suitable tocolytic targets. In addition, ten
cytokines in human cervico-vaginal fluid (CVF) were measured according to interval
to labour to test their suitability as labour onset predictors, with a view to developing
a test to determine women at risk of preterm labour.
Prostanoid analysis was carried out in endometrium (n=9) and myometrium (n=15-
16) donated by non-pregnant women and lower segment myometrium obtained from
pregnant women (before (n=14) and after labour onset (n=7)) by liquid
chromatography coupled with electrospray ionisation mass spectrometry (LC/ESIMS/
MS). Cytokines produced by CVF collected from pregnant donors (20-41
weeks gestation, n=2-10) were investigated using Enzyme-Linked Immunosorbent
Assay (ELISA) or Luminex®.
Human endometrium produced greater concentrations of TXB2, PGE2 and PGF2¿
than myometrium in vitro (p<0.05). Fifteen prostanoids were detected in human
myometrium. Production of 6-keto-PGF1¿, PGE1 and PGF1¿ increased whilst 15-
keto PGE2 and PGJ2 decreased at term pregnancy (37-41 weeks gestation) versus
non-pregnancy (p<0.05). Myometrium from parturient donors synthesised TXB2
and PGE2 more abundantly than the non-labouring equivalent. Cytokine
concentration was greatest in CVF sampled the week before labour, in particular
Interleukin-6 (IL-6), Macrophage Inflammatory Protein-1¿ (MIP-1¿) and Monocyte
Chemotactic Protein-1 (MCP-1) (p<0.05).
Endometrial TXB2, PGE2 and PGF2¿ could aid in proliferation of glandular
epithelium prior to ovulation. Prostacyclin may facilitate prolongation of pregnancy
to term and thromboxane could contribute to uterine stimulation during labour.
Cervical dilation may be influenced by PGE2 in lower segment myometrium. MCP-
1, MIP-1¿ and IL-6 could mark a short interval to labour onset. / Allergan Inc.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/5755 |
| Date | January 2012 |
| Creators | Garvin, Joanne H. |
| Contributors | Marshall, Kay M., Nicolaou, Anna |
| Publisher | University of Bradford, The School of Pharmacy |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Thesis, doctoral, PhD |
| Rights | <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>. |
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