Developmental consequences of trace mineral deficiencies in rodents: acute and long-term effects.

Approximately 3% of infants born have at least one serious congenital malformation. In the U.S., an average of 10 infants per thousand die before 1 y of life; about half of these deaths can be attributed to birth defects, low birth weight or prematurity. Although the causes of developmental abnormalities are clearly multifactorial in nature, we suggest that a common factor contributing to the occurrence of developmental abnormalities is suboptimal mineral nutrition during embryonic and fetal development. Using zinc and copper as examples, evidence is presented that nutritional deficiencies can rapidly affect the developing conceptus and result in gross structural abnormalities. Deficits of zinc or copper can result in rapid changes in cellular redox balance, tissue oxidative stress, inappropriate patterns of cell death, alterations in the migration of neural crest cells and changes in the expression of key patterning genes. In addition to well-recognized malformations, mineral deficiencies during perinatal development can result in behavioral, immunological and biochemical abnormalities that persist into adulthood. Although these persistent defects can in part be attributed to subtle morphological abnormalities, in other cases they may be secondary to epigenetic or developmental changes in DNA methylation patterns. Epigenetic defects combined with subtle morphological abnormalities can influence an individual's risk for certain chronic diseases and thus influence his or her risk for morbidity and mortality later in life.