The mammary gland undergoes important anatomical and physiological changes from embryogenesis through puberty, pregnancy, lactation and involution. These steps are under the control of a complex network of molecular factors, in which epigenetic mechanisms play a role that is increasingly well described. Recently, studies investigating epigenetic modifications and their impacts on gene expression in the mammary gland have been performed at different physiological stages and in different mammary cell types. This has led to the establishment of a role for epigenetic marks in milk component biosynthesis. This review aims to summarize the available knowledge regarding the involvement of the four main molecular mechanisms in epigenetics: DNA methylation, histone modifications, polycomb protein activity and non-coding RNA functions.

In mammals, milk is essential for the growth, development, and health. Milk quantity and quality are dependent on mammary development, strongly influenced by nutrition. This review provides an overview of the data on nutritional regulations of mammary development and gene expression involved in milk component synthesis. Mammary development is described related to rodents, rabbits, and pigs, common models in mammary biology. Molecular mechanisms of the nutritional regulation of milk synthesis are reported in ruminants regarding the importance of ruminant milk in human health. The effects of dietary quantitative and qualitative alterations are described considering the dietary composition and in regard to the periods of nutritional susceptibly. During lactation, the effects of lipid supplementation and feed restriction or deprivation are discussed regarding gene expression involved in milk biosynthesis, in ruminants. Moreover, nutrigenomic studies underline the role of the mammary structure and the potential influence of microRNAs. Knowledge from three lactating and three dairy livestock species contribute to understanding the variety of phenotypes reported in this review and highlight (1) the importance of critical physiological stages, such as puberty gestation and early lactation and (2) the relative importance of the various nutrients besides the total energetic value and their interaction.

Background: Nutritional changes can affect future lactation efficiency. In a rabbit model, an obesogenic diet initiated before puberty and pursued throughout pregnancy enhances mammary differentiation, but when started during the neonatal period can cause abnormal mammary development in early pregnancy. The aim of this study was to investigate the impact of an unbalanced diet administered during the pubertal period only.Results: Consuming an obesogenic diet at puberty did not affect either metabolic parameters or certain maternal reproductive parameters at the onset of adulthood. In contrast, at Day 8 of pregnancy, epithelial tissue showed a lower proliferation rate in obesogenic‐diet fed rabbits than in control‐diet fed rabbits. Wap and Cx26 genes, mammary epithelial cell differentiation markers, were upregulated although Wap protein level remained unchanged. However, the expression of genes involved in lipid metabolism and in alveolar formation was not modified.Conclusion: Taken together, our results demonstrate that the consumption for 5 weeks of an obesogenic diet during the pubertal period initiates mammary structure modifications and affects mammary epithelial cell proliferation and differentiation. Our findings highlight the potentially important role played by unbalanced nutrition during critical early‐life windows in terms of regulating mammary epithelial cell differentiation and subsequent function in adulthood.

Optimizing rabbit does preparation during early life to improve reproductive performance is a major challenge for breeders. Does selected for reproduction have nutritional needs, which may not be supplied with the common practice of feed restriction during rearing in commercial rabbit production. Nutrition during early life was already known to influence metabolism, reproduction and mammary gland development later in life, in particular during pregnancy. The aim of this study was to analyze four different restriction feeding strategies during post-weaning and over the pubertal periods (high or moderate restriction feeding applied from 5 to 9 weeks of age and/or restricted or ad libitum over the following 3 weeks constituting the pubertal period). Unlike food intake, which remains regular, mean body weight gain was inversely proportional to the dietary restriction applied over the considered periods. The feeding strategies in place for the four groups have no effect on the reproductive parameters of the females, as opposed to certain metabolic parameters such as cholesterolemia, that vary with dietary intake. Furthermore, restriction programs have impacted mammary tissular structures at mid-pregnancy. The expression of lipid metabolism enzymes (Fatty acid synthase N and Stearoyl co-A desaturase) is also modified in mammary epithelial cells by the dietary strategies implemented. Moreover, milk gene expression, used as differentiation markers, indicates a better mammary epithelial development regarding further lactation, in the case of the less restrictive strategies during early life period, especially the higher feeding allowance. Our results highlight the importance of investigating feeding conditions of young female rabbits and nutrition in early life rearing, in order to provide specific recommendations for optimizing lactation and thus preventing neonatal mortality of the offspring.

L’alimentation peut influencer le développement mammaire des femmes et compromettre la santé de la descendance. La leptine pourrait jouer un rôle majeur dans ces processus. Nous avons montré que chez la lapine, la synthèse mammaire de leptine était peu élevée en gestation puis augmentait en lactation, et que l’allaitement par une mère hyperadipeuse potentialisait les effets d’un régime obésogène ultérieur et induisait un développement mammaire anormal de la descendance. Nous avons également caractérisé la synthèse et la sécrétion mammaire de leptine, dans un modèle cellulaire hétérologue. Enfin, nous avons évalué la variation intra espèce ainsi que la croissance selon deux fenêtres nutritionnelles : alimentation obésogène administré dès la puberté ou dès la naissance, dans deux lignées murines, FVB/N et C57BL/6.Ce travail montre que la composition du lait maternel est altérée par l’alimentation et influe sur la croissance et le développement mammaire de la descendance, chez le lapin