Effects of Folic Acid Deficiency on the Murine Mammary Gland

Abstract

The epithelial ducts within the mammary glands (MG) undergo phases of isometric and allometric growth during early, postnatal life. Breast cancer is suggested to have origins in early life, a period during which folate requirements are high. We investigated the effects of folic acid (FA) on early MG development. Dams were assigned to either a control (2 mg FA/kg), deficient (0 mg FA/kg), excess (5 mg FA/kg), or super excess (20 mg FA/kg) amino acid defined diet and offspring continued to receive the same diet as their respective dams through postnatal and pubertal development. MG tissues from offspring were assessed at weaning and in early puberty. We observed no significant effects of excess or super excess FA diets on the MG. The area occupied by the mammary ducts at weaning and during early puberty was reduced in FA deficient animals compared with controls (p<0.0001). The rate of MG growth in the isometric phase, from birth to weaning, was less for the MG of deficient females compared with those from controls (slope 95% confidence limits 0.23‐0.78 versus 1.47‐1.82, respectively). The subsequent rate of allometric growth was unaffected by diet. The supramammary lymph nodes in deficient animals were smaller than in control animals alongside a reduction in the area of the thymic medulla. Epigenetic and local expression analysis of signaling and growth factors in the MG are ongoing. We conclude that dietary FA deficiency alters normal development of the epithelial ducts and lymph node in the MG of prepubertal female mice. Funding source: CA Breast Cancer Research Program Grant #18IB‐000