The influence of the hormonal milieu on eicosanoid and cytokine production in tissues from the female reproductive tract

Joanne Helen Garvin
2012 · W2026909881
dissertation OA: closed CC0 Metadata only
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This study measured prostanoid profiles in human uterine tissues and cytokine concentrations in cervicovaginal fluid across pregnancy and labor, identifying specific molecules associated with labor onset and potential roles in pregnancy maintenance.

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Abstract

In the human uterus prostaglandins (PG) PGE2, PGD2, PGI2, PGF2¿ and \nThromboxane A2 (TXA2), also termed prostanoids, are synthesised and deactivated \nto 15-keto PGE2, J2 metabolites, 6-keto-PGF1¿, 15-keto PGF2¿ and TXB2 \nrespectively. However, not all metabolites have been analysed simultaneously \nwithin the same tissue. The primary objective of this thesis was to determine full \nuterine prostanoid profiles in human non-pregnancy, pregnancy and parturition, to \nbetter understand these processes and find suitable tocolytic targets. In addition, ten \ncytokines in human cervico-vaginal fluid (CVF) were measured according to interval \nto labour to test their suitability as labour onset predictors, with a view to developing \na test to determine women at risk of preterm labour. \nProstanoid analysis was carried out in endometrium (n=9) and myometrium (n=15- \n16) donated by non-pregnant women and lower segment myometrium obtained from \npregnant women (before (n=14) and after labour onset (n=7)) by liquid \nchromatography coupled with electrospray ionisation mass spectrometry (LC/ESIMS/ \nMS). Cytokines produced by CVF collected from pregnant donors (20-41 \nweeks gestation, n=2-10) were investigated using Enzyme-Linked Immunosorbent \nAssay (ELISA) or Luminex®. \nHuman endometrium produced greater concentrations of TXB2, PGE2 and PGF2¿ \nthan myometrium in vitro (p<0.05). Fifteen prostanoids were detected in human \nmyometrium. Production of 6-keto-PGF1¿, PGE1 and PGF1¿ increased whilst 15- \nketo PGE2 and PGJ2 decreased at term pregnancy (37-41 weeks gestation) versus \nnon-pregnancy (p<0.05). Myometrium from parturient donors synthesised TXB2 \nand PGE2 more abundantly than the non-labouring equivalent. Cytokine \nconcentration was greatest in CVF sampled the week before labour, in particular \nInterleukin-6 (IL-6), Macrophage Inflammatory Protein-1¿ (MIP-1¿) and Monocyte \nChemotactic Protein-1 (MCP-1) (p<0.05). \nEndometrial TXB2, PGE2 and PGF2¿ could aid in proliferation of glandular \nepithelium prior to ovulation. Prostacyclin may facilitate prolongation of pregnancy \nto term and thromboxane could contribute to uterine stimulation during labour. \nCervical dilation may be influenced by PGE2 in lower segment myometrium. MCP- \n1, MIP-1¿ and IL-6 could mark a short interval to labour onset.

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