Role of compensatory mammary growth in epigenetic control of gene expression.

To better understand the role of nutrition in regulating mammary gland development and lactation, we designed a novel stair-step compensatory nutrition regimen that is a unique combination of dietary energy restriction and realimentation (refeeding) phases; the basic concept of this regimen is to exploit the biological nature of the compensatory growth phenomenon in concert with one or more hormone-sensitive allometric phases of mammary development (i.e., peripuberty through gestation). Nutritionally induced compensatory growth during different developmental stages before first parturition positively affects mammary development and life-long lactation performance. This permanent enhancement of mammary gland growth and lactation potential strongly suggests a possible mechanistic link between nutritionally induced compensatory growth, epigenetic control of mammary gene expression, and metabolic imprinting. We hypothesize that compensatory-directed metabolic imprinting once set during late pregnancy prior to the first parturition persistently maintains and exerts its adaptive response on mammogenesis and galactopoiesis (i.e., maintenance and/or enhancement of milk secretion). The ability to influence heritable genes regulating milk synthesis may be used to improve the quality and quantity of milk (e.g., infant health, the secretion of certain immunoglobulins or growth factors) as well as the longevity of lactation.