Hypoxic inhibition of human myometrial contractions in vitro: implications for the regulation of parturition

Background  Insufficient tissue oxygenation is a likely contribution to weak, inco-ordinate human uterine contractile activity characteristic of prolonged, dysfunctional labour. However, the direct effects of hypoxia on human myometrial contractility has, surprisingly, not yet been detailed. Therefore, we report the influence of hypoxia on spontaneous and agonist-induced carbachol, prostaglandin (PGF2α), and oxytocin contractions of myometria from nonpregnant and pregnant women. Materials and methods  Uterine biopsies were obtained from pregnant women at term undergoing elective Caesarean section and nonpregnant women undergoing hysterectomy. Myometrial strips were equilibrated at 37 °C in normoxic physiological salt solution (95% air/5% CO2) and the influence of hypoxia (95% N2/5% CO2) on contractility was investigated. Results  Hypoxia resulted in a significant reduction in spontaneous contractile function; nonpregnant tissue was less resistant to the deleterious effects of hypoxia. Agonist-induced contractions, while being more resistant to hypoxia than spontaneous contractions, were also significantly inhibited. In myometria of pregnant women the PGF2α- or oxytocin-induced contractility was more resistant to hypoxia than carbachol. Finally, the inhibitory actions of hypoxia were exacerbated with repeated oxytocin administration with a more severe effect on contractile integral than on initial phasic contraction amplitude. Conclusions  We detail, for the first time, the effects of hypoxia on contractility of human myometria from nonpregnant and pregnant women. Physiologically important uterotonic agents are more resistant to the effects of hypoxia than spontaneous contractions although repeated stimulation with oxytocin during hypoxia results in progressively less force. The results indicate that if significant hypoxia occurs in vivo then it is a likely contributory factor to the pathways underlying prolonged dysfunctional labour.