Sheep stress programs lamb

Early life of fetus affects organs’ future health.

Sheep stressed in early pregnancy bear lambs with stunted kidneys that predispose them to high blood pressure Australian researchers have shown. The finding adds to growing evidence that early fetal life influences adult health.

Marelyn Wintour of the University of Melbourne subjected 4-week-pregnant ewes to two stressful days by infusing them with the hormone cortisol. Their lambs developed high blood pressure at 5 months of age, she told the Experimental Biology 2002 meeting in New Orleans on Sunday.

Just before birth, genes that regulate kidney development and blood pressure are more active than normal, she and her colleagues went on to find. As adults, the animals had only two-thirds of the normal number of fluid-filtering units in their kidneys.

Stress forces the cells destined to form the kidney to mature too fast, Wintour believes. This would give the organ less time to grow. “We accelerated maturation by overexpression of these genes,” says Wintour. Over time, the inability of the kidney to expel water and salts efficiently may cause blood pressure to rise.

Wintour and others have explored the effects of maternal stress on the fetus before, but this is the first test of the effect of a natural hormone in a large animal. A 4-kilogram lamb weighs roughly the same as a human baby.

Premature physique

Fetal programming is the idea that early events in fetal growth affect an adult’s susceptibility to disease. It was discussed at two sessions of the New Orleans meeting.

Many large epidemiology studies have shown that poor nutrition, which limits fetal growth and reduces birth weight, is associated with increased risk of heart disease, hypertension and adult-onset diabetes.

“It takes it away from the idea that [these diseases] are retribution for adults,” says epidemiologist David Barker of the University of Southampton, UK, who originally proposed the fetal-programming hypothesis.

Barker suggests that when conditions are tough – when food is scarce or levels of stress hormones are high, say – the fetus adapts to ensure its survival, perhaps by diverting blood or nutrients to the brain at the expense of other organs. These shifts cause permanent changes in the adult organs. “Everyone has been changed by their experience in fetal life,” maintains Barker.

How fetal tissues are permanently altered remains largely unknown. Cells that give rise to an organ may be susceptible to external signals, suggests paediatric researcher Rebecca Simmons of the University of Pennsylvannia in Philadelphia. Anything that interrupts these signals could alter the cell types that survive to contribute to the organ.

This is consistent with Wintour’s finding that kidney development can be altered by stress that occurs even before it has formed. “It was surprising to me that the early time is the critical one,” she says.

At the equivalent point in human pregnancy – at around 5-7 weeks – many women are unaware of their condition. Pregnant women who know they are stressed should try and take a little time out to relax or sleep, Wintour suggests.