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1 Liggins Institute, University of Auckland, Auckland, New Zealand
2 Physiology and Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario, Canada
* To whom correspondence should be addressed. E-mail: j.harding{at}auckland.ac.nz.
In sheep, parturition is initiated by increased fetal hypothalamic-pituitary-adrenal axis (HPAA) activity leading to prostaglandin (PG) E2 and PGF2
production and a rise in the 17-estradiol:progesterone (E2:P4) ratio. Uteroplacental PG production can also increase fetal HPAA activity. Periconceptional maternal undernutrition accelerates fetal HPAA maturation resulting in preterm labor. We determined if preterm labor was preceded by an increase in PG concentrations and E2:P4 ratio, and whether these increases preceded or followed the corresponding rise in cortisol concentrations. Singleton bearing ewes were either nourished ad libitum ("N", n=9) or undernourished ("UN", n=10) to reduce maternal weight by 15% from -61d to +30d after mating with ad libitum intake thereafter. Paired maternal and fetal blood samples were collected from 126 d until delivery. Half the UN group delivered prematurely (>2SD below mean gestation for the flock). PG and cortisol concentrations, and E2:P4 ratio, increased prior to delivery in the same way in both N and UN groups. However, the increases occurred 7-10d earlier in UN than in N animals. In both UN and N fetuses cortisol concentrations rose before fetal and maternal PG concentrations and maternal E2:P4 ratio. Periconceptional maternal undernutrition induces preterm delivery in sheep by advancing the expected prepartum rise in cortisol and PG concentrations and E2:P4 ratio. The rise in fetal cortisol concentration precedes the rise in fetal and maternal PG concentrations and maternal E2:P4 ratio, suggesting that the underlying mechanism is likely to be acceleration of fetal HPAA maturation resulting in initiation of the normal process of parturition.
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