Postpubertal development of the rat mammary gland is preserved during irondeficiency

We previously showed that moderate iron deficiency is associated with incre ased susceptibility to chemically induced breast carcinogenesis. Epidemiolo gical and experimental data suggest that breast cancer risk may be modulate d by the developmental and proliferative state of the mammary epithelium, T he adverse effects of iron deficiency on organ growth are well documented. However, the role of iron in mammary gland development has not been examine d. Therefore, we studied the effect of iron deficiency on mammary gland dev elopment and epithelial cell kinetics in female Sprague-Dawley rats. Weanli ng 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 bloo d hemoglobin were lower in iron-restricted rats than in controls, with sign ificant differences from controls observed in rats receiving 6 mg Fe/kg die t (P < 0.05). Liver iron was reduced 90 and 80% in severe and moderate grou ps, respectively, compared with controls. Puberty onset and 17-beta -estrad iol levels were unaltered by iron status, but plasma progesterone was signi ficantly lower in iron-restricted groups (P < 0.05). Microscopic examinatio n of mammary gland whole mounts revealed an increased density of terminal e nd buds in thoracic glands from iron-restricted rats, indicative of decreas ed differentiation, although the differences were not statistically signifi cant compared with controls (P = 0.21). Mammary epithelial cell proliferati on, determined in contralateral glands by measuring 5-bromo-2 ' -deoxyuridi ne 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.