Fetal control of parturition in marsupials.

Among marsupials, the control of birth is best understood in the tammar wallaby. The young is tiny relative to the mother and is highly altricial. Adult female tammar wallabies weigh 5 kg, whereas the neonate weighs about 400 mg. However, despite this small size, there is clear evidence that the fetus provides the signal that sets the timing of birth through several mechanisms. A fetal signal activates a nitric oxide-guanylate cyclase system in the myometrium that may maintain myometrial inactivity, and this is down-regulated at term. There is also up-regulation of prostaglandin (PG) production in the gravid endometrium during the last two days of gestation that parallels increased placental PG synthesis, and a pregnancy-specific up-regulation of oxytocin receptors in the gravid myometrium that increases the responsiveness of the gravid uterus to mesotocin. These changes facilitate parturition, but an acute fetus-derived signal appears to trigger parturition. The fetal signal is probably related to glucocorticoid production. The fetal adrenal matures and is able to synthesize cortisol by Day 22 of the 26-day gestation. The fetal adrenals double in size between Day 24 and term, and their cortisol content increases over 10-fold. The pituitary of the neonate contains presumptive corticotrophs, and the adrenals increase cortisol production in response to adrenocorticotrophin. Prostaglandin E2, which is produced by the placenta, is also a potent stimulant of fetal adrenal cortisol synthesis. Treatment of tammars in late gestation with the cortisol agonist, dexamethasone, triggers birth around 23 h later. There is thus a strong case that fetal adrenal cortisol plays a key role in the preparation for birth and the timing of it. Further studies are in progress to more clearly define the mechanisms behind these actions of cortisol.