Nutritional regulation of uteroplacental prostaglandin production and metabolism in pregnant ewes and mares during late gestation.

Prostaglandins (PGs) are produced by a variety of uteroplacental tissues during pregnancy and are released into the fetal fluid sacs and both the uterine and umbilical circulations. Uterine PG output increases towards term and is enhanced by maternal undernutrition in pregnant ewes and mares. In both species, withdrawal of food but not water for 30-48 h increases uterine venous PG levels and the uterine venous arterial concentration differences in PGE and 13, 14, dihydro-15-keto-prostaglandin F2 alpha (PGFM), the stable metabolite of PGF2 alpha. The increments in uterine V-A concentration differences in PGE and PGFM increase towards term and are associated with raised plasma PG levels in the fetal circulation. The PG changes observed during fasting are closely related to the fall in plasma glucose and the rise in plasma FFA in peripheral plasma. When normal metabolite levels are restored either by refeeding or glucose infusion, there is a rapid fall in PG levels with a narrowing of the uterine V-A concentration differences in the ewe and mare. When the data from all the animals are combined, there is an inverse correlation between uterine glucose uptake and PGFM output in both the pregnant ewe and mare. The availability of glucose and FFA to the gravid uterus therefore has an important role in controlling uteroplacental PG production and metabolism in late gestation although the specific steps in biochemical pathways regulated by these metabolites remain unclear. In the ewe, fasting increases uterine contractility and leads to early delivery of viable lambs in animals close to term (> 95% gestation), whereas in the mare it causes premature delivery of non-viable foals in most animals in late gestation (> 80% gestation). Nutritionally induced changes in uteroplacental PG production and metabolism therefore have important consequences for the outcome of pregnancy and may have a pivotal role in the induction of labour both before and at normal term.