The rats were tested before and during pregnancy, and then several generations of their offspring were examined. The study, by a team including Newbold and Barry Delclos of the National Center for Toxicological Research, was published in the journal in April.
In male rats, high doses led to abnormal growth of breast cells, but did not cause cancer or the feminization of reproductive organs, according to another study by Newbold and others published in November.
In those two studies, the rodents were fed at least five times more genistein than the amount that people would be exposed to through food, supplements or infant formula. Such a high dose was used because they wanted to test the effects of the maximum amount that could be ingested by the rats without severely limiting their ability to reproduce.
The growing body of research in recent years raises questions about possible risks to women trying to get pregnant, as well as to developing fetuses and infants who consume large amounts of genistein in formula, some researchers said.
The findings trouble Heather Patisaul, a developmental biologist at North Carolina State University, and others who study soy's impact on development.
“Our reproductive system and the rat reproductive system aren’t that different. The same hormones are involved," Patisaul said.
While any impacts on adult fertility are likely reversed by eating less soy, impacts on the reproductive tracts of infants could be permanent.
But to date, only one study has looked at the long-term effects of soy formula on reproductive development in people. It found that women fed soy formula as infants had slightly longer periods and more menstrual cramping than those who were not fed soy formula.
Brain development, which begins in the womb and continues through puberty, also may be altered by estrogen in soy, Patisaul said. It is controlled by a well-organized combination of genes and hormones. Introducing compounds that mimic estrogen could throw off the balance, with long-term impacts on behavior and brain chemistry.
Studying the health outcomes of fetal or early infant exposure can be difficult, according to Benson Akingbemi, a developmental biologist at Auburn University. Reproductive changes are often not apparent until adulthood.
Another difficulty is that infant formulas vary in isoflavone content depending on the type of soybean used and the conditions—such as soil type—that the beans were grown in, making dosage very hard to control.
In 2008, the American Association of Pediatricians reviewed all current scientific studies of the effects of soy formula on infants. There is no conclusive evidence that it harms infant development, reproduction or endocrine function, stated the American Association of Pediatricians.
Based on current research, “no changes in infant feeding practices are recommended,” wrote Haley Curtis, a scientific affairs specialist at the International Formula Council, in an email. “Infant formula is safe and nutritious.”
But Akingbemi believes that limiting exposure wouldn’t hurt.
“The current scientific evidence isn’t enough to say that exposure to these compounds is toxic, but we also can’t say with certainty that there is no effect,” he said.
Some researchers believe that waiting for proof from long-term human data may come at a price.
Patisaul compares the effects of genistein to Bisphenol A, or BPA, the estrogenic compound found in plastic bottles that many scientists suspect can harm brain and reproductive development.
“Genistein does the same thing and yet we are supposed to be eating tons of it because it’s supposedly healthy—it just doesn’t make sense,” she said.
This article originally ran at Environmental Health News, a news source published by Environmental Health Sciences, a nonprofit media company.