This study may play a major role in determining how these compounds cause early-onset puberty and symptoms of advanced menopause in research animals, as well as in providing a key building block for how to treat these problems.
It is the first study to show that the actual physical organization of a region of the brain that is important for female reproduction can be significantly altered by exposure to phytoestrogens - or plant-produced chemicals that mimic hormones - during development.
The study found that the compounds alter the sex-specific organization of the hypothalamus - a brain region that is essential to the regulation of puberty and ovulation. It also shows that the phytoestrogens could cause long-term effects on the female reproductive system.
The study examined the impact of these compounds on laboratory rats, while neurotoxicologist Dr. Heather Patisaul - who co-authored the study - said the affected "circuitry" of the brain is similar in both rats and humans. She said that this study is also "a step towards ascertaining the effects of phytoestrogens on developing fetuses and newborns."
In the study, newborn rats were exposed to physiologically relevant doses of the phytoestrogens genistein and equol, and then the researchers looked at reproductive health markers in the rats throughout their adulthood.
Patisaul said that the neonatal stage of development in rats is comparable to the latter stages of pregnancy for humans. Genistein is a phytoestrogen that is found in various plants, including soybeans and soy-based foods. Equol is a hormone-like compound that is formed when bacteria found in the digestive system metabolize another phytoestrogen. However, only approximately a third of humans have the necessary bacteria to produce equol.
The study shows that both genistein and equol result in the early disruption of the rats' estrus cycle - which would be corollary to early onset of menopause in a human.
The study also showed that genistein caused the early onset of puberty. The disruption of the estrus cycle could stem from problems with the brain or the ovaries, so the researchers decided to determine if the compounds had any effect on brain development or function.
Patisaul explained that the brains of both female rats and female humans have a region that regulates ovulation.
"That part of the brain. is organized by hormones during development - which is the neonatal stage for rats and during gestation for humans," Patisaul says.
She said that the new study shows that the female brain is "critically sensitive" to genistein and equol during this crucial stage of development - and that this may indicate that the brain is also especially sensitive during this period to all phytoestrogens and possibly other man-made chemicals, such as bisphenol-A.
The study is published in an upcoming issue of Neurotoxicology.