Stimulation of the switch in myometrial activity from contractures to contractions in the pregnant sheep and nonhuman primate

The process of parturition is regulated by a set of interrelated endocrine, paracrine, and autocrine systems. Many of these systems demonstrate positive feed-forward characteristics. The sequential recruitment of signals that promote the labour process demonstrates that it is not possible to attribute the designation of the factor responsible for the 'initiation of parturition' uniquely to any one signalling mechanism. For this reason we prefer to avoid the term initiation of parturition since, mechanistically, each cellular and molecular mechanism that contributes to the process is itself initiated by an earlier process. In a very real sense, the initiation of parturition can be considered to be fertilisation. Therefore we prefer to describe the key mechanisms involved as promoting, rather than initiating, the process of labour and delivery. Despite many interspecies differences, an increase in maternal plasma oestrogen in late gestation appears to play a central role in promotion of parturition. In both sheep and monkeys signals from the fetal hypothalamo-pituitary-adrenal axis increase oestrogen production by the placenta. We propose that the key fetal adrenal product is cortisol in the sheep and androgen in the monkey. Oestrogen then recruits a range of stimulators, uterotonins, that act on the prepared myometrium to initiate the switch in myometrial activity from contractures to contractions. The various mechanisms central to the process can be considered to be either, or both, activators and/or stimulators of one or more of the key terminal steps involved.