The researchers hope that the findings in zebrafish could contribute to treatments for children with Menkes disease, a rare genetic disorder that inhibits the absorption of copper before birth. Menkes affects approximately one in 300,000 people and is usually fatal within the first 10 years of life.
In the zebrafish -- chosen because their embryos develop rapidly and subsequently display the effects of deficiencies from the moment of fertilization -- copper was found to contribute to the formation of the notochord, which helps develop the spinal chord and other tissues in higher vertebrates such as humans.
"Our observations that copper is essential for notochord structure raise the intriguing possibility that suboptimal copper availability, due either to dietary factors or genetic variation during the period of notochord formation or subsequent bone formation, may contribute to structural birth defects such as congenital scoliosis," said pediatrician Jonathan Gitlin, referring to the condition marked by curvature of the spine.
"Copper deficiency is more common than many doctors and consumers realize," explained Mike Adams, a consumer health advocate and author of The Seven Laws of Nutrition. "With our crop soils depleted of minerals like copper, it is more important than ever to educate expectant mothers about the importance of nutritional supplementation to replenish copper and other essential nutrients," Adams said.
The study, published in the August issue of Cell Press' journal Cell Metabolism, inhibited the metabolism of copper in the zebrafish through the use of drugs and found that the fish lost pigment and showed altered notochord development. Abnormal cartilage, vascular and neurological development were also observed, the researchers reported.
The length of time the zebrafish were exposed to the drug was also determined to be important, as those that underwent a 10 minute treatment lost pigment but developed their notochord normally, a 20 minute treatment caused both a loss of pigment and a visibly abnormal notochord, and a 60 minute treatment resulted in additional defects alongside both of the previously observed conditions.
One zebrafish was not given the drug, but was found to have mutated copper transport genes -- known as ATP7A -- which is a known cause of Menkes disease. When the scientists inserted a normal human copy of ATP7A into the zebrafish, its developmental defects reversed. According to the researchers, this means pharmaceuticals that restore ATP7A deficiencies and restore copper enzyme function should be tested, as they could be important to treating Menkes disease.
The study authors added that more zebrafish studies could reveal new information about the role of gene-nutrient interactions in human development, and could help improve natal care and reduce birth defect risk.
"While it will require an enormous amount of science, this is the first time it is even within our grasp to know how an individual woman's genes might affect her nutritional requirements and the risk that her children might develop a congenital disorder," Gitlin said. "Ultimately, that information could allow us to provide for every woman a recipe for what is right for her pregnancy."
###