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Myometrial hypoxia and the role of pro-resolution mediators
  1. E Golightly1,
  2. H N Jabbour2,
  3. J E Norman1
  1. 1University of Edinburgh, Edinburgh, UK
  2. 2Medical Research Council Human Reproductive Sciences Unit, Edinburgh, UK

Abstract

Introduction Labour is an inflammatory process, and is likely to be influenced by pro-inflammatory and anti-inflammatory mediators. We have proposed recently a role for FPR2 (the receptor for the anti-inflammatory, pro-resolution mediator lipoxin A4 (LXA4)) in regulating inflammatory pathways in the human myometrium during labour.1 With prolonged labour the myometrium becomes relatively hypoxic, which may contribute to ineffective contractions and lack of progress in labour. In this study we investigate the effect of hypoxia on the production of LXA4 in myometrium.

Methods Myometrial explants from biopsies taken from term non-labouring women were cultured for 24 h in varying oxygen concentrations, 21%, 6% and 0.5% (n=5). Total RNA was extracted from the explants and RT-PCR used to determine relative mRNA expression of ALOX5, an enzyme involved in LXA4 synthesis; FPR2; and VEGF. Explant release of LXA4 into the culture supernatant was assessed by ELISA.

Results Relative mRNA expression of VEGF increased with increasing hypoxia, demonstrating hypoxic experimental conditions (ANOVA, p=0.0009). Relative mRNA expression of FPR2 was reduced in explants cultured in hypoxic conditions (ANOVA, p=0.02) although ALOX5 mRNA expression and LXA4 secretion were unaffected.

Discussion These results suggest that the human myometrium may become less responsive to anti-inflammatory/pro-resolution mediators in hypoxic conditions. Decreased signalling through FPR2 will likely maintain elevated levels of myometrial pro-inflammatory cytokines. Future work will investigate the role of FPR2 in human labour, and the combined effect of hypoxia and inflammation on myometrial contractility.

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