Fetal Growth Restriction Results in Increased Mammary Tumor Development

While a significant body of evidence indicates size at birth is linked to the development of a variety of metabolic and cardiovascular disorders in adulthood, the connection between birth weight and incidence of cancer is less clear. Recent studies have identified insulin like growth factors (IGFs) as important molecules in carcinogenesis. Thus, we hypothesized that placental insufficiency alters fetal IGF levels and increases incidence of mammary gland cancer in the offspring. To this end we, employed our well characterized model of reduced utero‐placental perfusion (RUPP) that results in placental insufficiency to generate fetal tissues and growth restricted offspring. Mammary cancers were induced in vivo in normal pregnant (NP) and RUPP offspring at weaning (21 days), by injection of 50 mg 1‐methyl‐1nitrosouraea (NMU)/kg body weight or DMSO. Fetal hepatic IGF‐2 levels were increased (155.6 ± 12.6 vs. 117 ± 6.3 pg/mL; p<0.05) in RUPP fetuses and mammary gland tumors developed 4 weeks earlier in the RUPP‐NMU offspring, prior to their NP‐NMU counterparts (p<0.01). The present data demonstrate for the first time that fetal growth restriction associated with placental insufficiency results in increased incidence of mammary tumor development. Moreover, this is associated with increased expression of a potent fetal growth factor that plays an important role in the development and progression of cancer.