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.
Central blockade of oxytocin receptors during mid-late gestation reduces amplitude of slow afterhyperpolarization in supraoptic oxytocin neurons