| We have developed a compensatory nutrition regimen (CNR) that is a combination of dietary energy restriction and refeeding phases designed to induce compensatory mammary growth that coincides with hormone-sensitive developmental stages.{09}Our objective was to study the effect of a CNR imposed during gestation on mammary development and lactation potential during the first and second lactation cycles.; Female rats were mated and randomly assigned to either the control or the CNR group. Control rats were offered a control diet (AIN-93G) throughout the experiment. CNR rats were subjected to 40% energy restriction during the first 10 days of gestation, followed by free access to the control diet for the remainder of the experiment. Upon completion of the nutrition regimen, which coincided with parturition, all rats were offered free access to the control diet until fulfillment of the first lactation cycle. Two weeks after weaning, all remaining dams were mated for a second breeding and offered free access to the control diet throughout the entire second cycle of lactation. Mammary samples were obtained from early and late lactating rats during the two lactation cycles.; The CNR rats gained minimal weight during the restriction period, but during the refeeding period, they exhibited compensatory growth and eventually attained similar weight as that of the control group. Expression profiling by gene array analysis revealed that various genes associated with a broad range of metabolic pathway or physiological function (i.e., proliferation, differentiation, secretion, cellular communication, apoptosis, lipogenic pathway, myogenic pathway, and tissue remodeling) were affected by CNR. Mammary cell proliferation rates were increased by CNR during late gestation and early lactation. Programmed cell death, indicated by caspase-3 enzyme activity, was reduced in the CNR group during late lactation. Interestingly, expression of these genes was altered during the second lactation cycle, suggesting that the functional activity of the mammary gland induced by our CNR may be permanently maintained. Our CNR imposed during gestation altered the activity of mammary cells and subsequently enhanced life-long lactation potential. |
