INITIATION OF PARTURITION

Dysfunctional parturition is a major contributor to perinatal mortalit y and morbidity, yet our knowledge of the mechanisms that initiate lab or is limited. While the endocrine profiles across species are quite d iverse, several common threads are apparent, foremost of which is a re quirement for progesterone to maintain pregnancy. I propose that at te rm, progesterone must be physically or functionally removed, resulting in a switch from a progesterone dominated to an estrogen dominated sy stem. This increase in the estrogen:progesterone ratio causes the mobi lization of two parallel molecular/biochemical pathways. One leads to myometrial ACTIVATION, an increase in myometrial spontaneous excitabil ity, responsiveness to uterotonic stimulants and cell-cell coupling as a result of the increased expression of a cassette of 'contraction-as sociated' proteins, such as ion channels, agonist receptors and gap ju nctions. The other leads to the increased production and release of th e uterotonic agonists to STIMULATE the activated myometrium. The tempo ral coordination and synchronization of these pathways ensures the eff icient and expeditious delivery of the fetus(es). Understanding the me chanisms regulating these pathways should enable the development of pr otocols to prevent premature labor in women, and also effectively mani pulate the timing of birth in domestic species, thereby reducing perin atal loss and enhancing productivity.