ACTH-induced preterm labour in the ewe is associated with increased mRNA and protein levels of myometrial gap junction protein, connexin-43

The myometrial gap junction protein, connexin-43, is thought to be critical to the development of synchronous, high-amplitude contractions of the myometrium during labour. The purpose of this study was to determine the relationship between the temporal expression of myometrial connexin-43 mRNA and protein, the contractile patterns of the uterus and the changes in maternal plasma oestrogen and progesterone. On day 127 chronically catheterized fetal sheep were randomized to receive either ACTH (1 μg over 15 min every 2 h) or saline (control) infusions. Using this model, ACTH induces labour in 110 ± 5 h and produces similar endocrine profiles and changes in myometrial activity to that of term spontaneous labour. Myometrial tissue was obtained during autopsy at: 0 h (127 days: no infusion), 72 h saline, 72 h ACTH, 120 h saline, and during ACTH-induced labour (n=4/group). Northern analysis demonstrated a significant (P<0.05) increase in connexin- 43 transcripts during labour (2.21 ± 0.39; mean ± S.E.M. relative to 18S) compared with 0 h (0.67 ± 0.17) and 72 h ACTH (0.41 ± 0.11). Connexin-43 protein (as determined by Western analysis) showed a similar pattern to that of the transcripts. These changes in myometrial connexin-43 expression were associated with significant increases in the rate of rise of intrauterine pressure, frequency and maximum amplitude of uterine contractions and the maternal plasma oestrogen to progesterone ratio. No changes in connexin-43 expression, contractile parameters or endocrine profiles occurred in control animals. Our data suggest that the increased myometrial contractile coordination during preterm labour in the sheep is, at least in part, due to a steroid-associated increase in connexin-43 expression.