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Title: The relationship between pro-inflammatory cytokines and prostaglandin production in the human amnion
Author: Das, Ananya
ISNI:       0000 0004 7427 7395
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2018
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Preterm labour (PTL) management may be improved through better understanding of term labour. Existing research suggests that myometrial inflammation stimulates the initiation of labour at term. However, this theory has recently been challenged by group data, derived from a collection of gestational tissues. In this thesis, amnion samples were selected and prolabour gene expression, inflammation and the steroid receptor pathways for the glucocorticoid and progesterone receptors (PRs) studied. It was hypothesised that (i) amnion inflammation occurs in early labour (TEaL) and, consequently, may have a role in the onset of human parturition; (ii) prolabour gene expression is increased in amnion samples in TEaL and that (iii) both are related to a decline in progesterone (P4) signalling. It was also speculated whether (iv) P4 acts via PRs and not glucocorticoid receptors (GRs) and whether (v) P4 function in the amnion can be enhanced by the addition of cyclic AMP were investigated. Analysis suggested that amnion inflammation occurs predominantly in TEsL but also in TEaL leaving it unclear whether amnion inflammation has a role in human labour onset. Increased prolabour gene expression was observed more significantly in TEsL and in PTL, was dependent on the underlying aetiology. Human amnion epithelial cells were acquired from women undergoing term elective caesarean section. Cells were treated with P4 and a cAMP agonist, forskolin, independently and in combination, to investigate whether the effects of an in vitro IL-1β treatment may be reduced, in the presence and absence of mechanical stretch. Both P4 treatment alone, as well as P4 +F treatment reduced IL-1β-driven expression. However, stretch-induced changes in expression could not be reduced through P4 treatment, alone or in combination with forskolin. P4 maintained its capacity for reducing IL-1β driven COX-2 mRNA expression in the absence of GR, whilst overexpressing PR isoforms enhanced P4-driven action.
Supervisor: Johnson, Mark ; Sooranna, Suren Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral