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Fetal Physiological Programming

Effects of periconceptional undernutrition on the initiation of parturition in sheep

¹Liggins Institute, University of Auckland, Auckland, New Zealand; and ²Departments of Physiology and Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario, Canada

Submitted 1 June 2004 ; accepted in final form 19 August 2004

In sheep, parturition is initiated by increased fetal hypothalamic-pituitary-adrenal axis (HPAA) activity leading to PGE₂ 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 whether 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 nourished ad libitum (N, n = 9) or undernourished (UN, n = 10) to reduce maternal weight by 15% from –61 days (d) to +30 d 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 (>2 SD below mean gestation for the flock). PG and cortisol concentrations and E₂/P₄ ratio increased before delivery in the same way in both groups. However, the increases occurred 7–10 d 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.

hypothalamic-pituitary-adrenal axis; prostaglandin; cortisol; estrogen-progesterone ratio

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