Postpubertal development of the rat mammary gland is preserved during iron deficiency

We previously showed that moderate iron deficiency is associated with increased susceptibility to chemically induced breast carcinogenesis. Epidemiological and experimental data suggest that breast cancer risk may be modulated by the developmental and proliferative state of the mammary epithelium. The adverse effects of iron deficiency on organ growth are well documented. However, the role of iron in mammary gland development has not been examined. Therefore, we studied the effect of iron deficiency on mammary gland development and epithelial cell kinetics in female Sprague-Dawley rats. Weanling rats were fed experimental diets that provide 6 (severe), 12 (moderate) or 35 (control) mg Fe/kg diet. After 6 wk of treatment, hematocrit and blood hemoglobin were lower in iron-restricted rats than in controls, with significant differences from controls observed in rats receiving 6 mg Fe/kg diet (P < 0.05). Liver iron was reduced 90 and 80% in severe and moderate groups, respectively, compared with controls. Puberty onset and 17-beta-estradiol levels were unaltered by iron status, but plasma progesterone was significantly lower in iron-restricted groups (P < 0.05). Microscopic examination of mammary gland whole mounts revealed an increased density of terminal end buds in thoracic glands from iron-restricted rats, indicative of decreased differentiation, although the differences were not statistically significant compared with controls (P = 0.21). Mammary epithelial cell proliferation, determined in contralateral glands by measuring 5-bromo-2'-deoxyuridine incorporation, did not differ between rats receiving 12 and 35 mg Fe/kg diet. In conclusion, these results suggest that alveolar development of the mammary gland and the proliferative capacity of the mammary epithelium are refractory to iron deficiency during early postpubertal growth of the rat.