Failed induction of human labour is associated with an altered myometrial phosphoproteome

Induction of labour (IOL) is increasingly recommended for a variety of maternal and fetal indications. Approximately 30% of labours that are induced result in an emergency caesarean section (failed induction of labour). We have previously reported that the feto-placental metabolome of spontaneous labour is not reproduced by current methods of IOL. Here, we have investigated the myometrial phosphoproteome and found an altered phenotype associated with failed IOL. We conducted global phosphoproteomics analysis of human myometrium obtained at the time of term elective caesarean section from women who had previously had a vaginal birth and compared with myometrium obtained at the time of emergency caesarean from women with a failed IOL. The myometrium was cut into strips and placed in an organ bath under different experimental conditions: pre-contracting; spontaneously contracting at peak contraction and peak relaxation; and oxytocin-induced contracting state at peak contraction and peak relaxation. Human myometrial proteins and phosphorylation events were differentially expressed in myometrium from women with failed IOL compared with myometrium from women with previous vaginal birth. This included changes within key pathways of cytoskeletal remodelling, extracellular matrix dysregulation, and defective metabolic adaptation; such differences may reflect an altered myometrial phenotype in failed IOL and open new areas of research to improve the clinical induction of labour.