Sci. Aging Knowl. Environ., 28 April 2004
From Womb the Bell Tolls
Stressing a fetus creates health problems that persist into old age
R. John Davenporthttp://sageke.sciencemag.org/cgi/content/full/2004/17/nf44
Years of lethargy and too many cheeseburgers can give a retiree diabetes, but adversity in the womb might also cultivate the condition. According to new work, aged rats display some signs of diabetes if their mothers were stressed during pregnancy. The research adds to evidence that fetal experiences can influence adult health, although scientists don't know how much the prenatal environment contributes to disease.
The "fetal origins hypothesis" arose after researchers found that babies born small because of malnutrition were unusually likely to die of heart problems as adults (see "From Womb to Tomb"). The outcome hinted that the uterine environment might be as important in adult health as are factors such as diet and smoking. Scientists proposed, for example, that scarcity prompts a fetus to alter metabolism to prepare for lean times and then abundant food after birth induces scourges such as heart disease and diabetes. Other human studies bolstered the idea, but detractors argued that the results were correlational and didn't prove that fetal deprivation was the cause of disease--only that the two tended to occur in the same people. To probe the hypothesis and potential mechanisms, researchers have studied a variety of creatures. Some work suggests that stress in utero plays a crucial role later. For example, when pregnant mother rats receive stress-steroid injections or are restrained--which elicits a stress response--their offspring frequently develop circulatory and metabolic problems, such as high blood pressure and diabetes. But researchers had examined young and middle-aged rodents, and no one had discerned whether fetal conditions impair health in old age.
To test that question, Lesage and colleagues placed 10 expectant female rats into constrictive tubes three times a day during the last week of their 21-day pregnancies. The researchers raised the offspring and analyzed their physiology when they were 2 years old--retirement age for rats. Animals from stressed mothers were lighter at birth than were those from unstressed mothers, but by 2 years of age their weight was normal. The oldsters from restrained moms carried higher concentrations of glucose in their blood, an indicator of diabetes. The animals weren't diabetic, however; blood insulin amounts were not elevated, a hallmark of the disease. The rodents also had reduced quantities of leptin, which clips appetite. However, the animals did not eat more than normal, although they gorged to a greater extent after a fast than did rats from unstressed mothers.
By showing that prenatal tribulations alter metabolism in old age, the results add to the fetal origins hypothesis, says molecular endocrinologist Jonathan Seckl of Edinburgh University in the U.K., but further work is needed to explain the mechanisms behind the observations. Peter Nathanielsz, a physiologist at New York University in New York City, agrees. He notes that although fetal conditions influence adult health, no one has determined how significant they are compared with bad habits acquired after birth. As research on the subject progresses, scientists should get a better idea of whether concern about old age should begin before birth.
April 28, 2004
Suggested by Adrienne Cashion.
Science of Aging Knowledge Environment. ISSN 1539-6150