Hue-Beauvais C, Koch E, Chavatte-Palmer P, Galio L, Chat S, Letheule M, Rousseau-Ralliard D, Jaffrezic F, Laloë D, Aujean E, Révillion F, Lhotellier V, Gertler A, Devinoy E, Charlier M
J Anim Sci. 2015 Apr;93(4):1641-55. doi: 10.2527/jas.2014-8139.
Alterations to the metabolic endocrine environment during early life are crucial to mammary gland development. Among these environmental parameters, the initial nutritional event after birth is the consumption of milk, which represents the first maternal support provided to mammalian newborns. Milk is a complex fluid that exerts effects far beyond its immediate nutritional value. The present study, therefore, aimed to determine the effect of the nutritional changes during the neonatal and prepubertal periods on the adult mammary phenotype. Newborn rabbits were suckled by dams fed a high-fat/high-sugar obesogenic (OD) or a control (CON) diet and then subsequently fed either the OD or CON diets from the onset of puberty and throughout early pregnancy. Mammary glands were collected during early pregnancy (Day 8 of pregnancy). Rabbits fed with OD milk and then subjected to an OD diet displayed an abnormal development of the mammary gland: the mammary ducts were markedly enlarged (P < 0.05) and filled with abundant secretory products. Moreover, the alveolar secretory structures were disorganized, with an abnormal aspect characterized by large lumina. Mammary epithelial cells contained numerous large lipid droplets and exhibited fingering of the apical membrane and abnormally enlarged intercellular spaces filled with casein micelles. Leptin has been shown to be involved in modulating several developmental processes. We therefore analyzed its expression in the mammary gland. Mammary leptin mRNA was strongly expressed in rabbits fed with OD milk and subjected to an OD diet by comparison with the CON rabbits. Leptin transcripts and protein were localized in the epithelial cells, indicating that the increase in leptin synthesis occurs in this compartment. Taken together, these findings suggest that early-life nutritional history, in particular through the milking period, can determine subsequent mammary gland development. Moreover, they highlight the potentially important regulatory role that leptin may play during critical early-life nutritional windows with respect to long-term growth and mammary function.
生命早期代谢内分泌环境的改变对乳腺发育至关重要。在这些环境参数中，出生后的初始营养事件是乳汁的摄入，这是母体为哺乳动物新生儿提供的首个支持。乳汁是一种复杂的液体，其作用远不止于直接的营养价值。因此，本研究旨在确定新生儿期和青春期前营养变化对成年乳腺表型的影响。新生兔由喂食高脂/高糖致肥胖（OD）或对照（CON）饮食的母兔哺乳，然后从青春期开始直至整个妊娠早期，分别喂食OD或CON饮食。在妊娠早期（妊娠第8天）采集乳腺。喂食OD乳汁然后接受OD饮食的兔子乳腺发育异常：乳腺导管明显增粗（P < 0.05），充满大量分泌产物。此外，腺泡分泌结构紊乱，管腔大呈现异常形态。乳腺上皮细胞含有大量大脂滴，顶端膜呈指状，充满酪蛋白微胶粒的细胞间隙异常增大。已证明瘦素参与调节多个发育过程。因此，我们分析了其在乳腺中的表达。与CON组兔子相比，喂食OD乳汁并接受OD饮食的兔子乳腺瘦素mRNA强烈表达。瘦素转录本和蛋白定位于上皮细胞，表明瘦素合成增加发生在该细胞区室。综上所述，这些发现表明生命早期的营养史，特别是哺乳期，可以决定随后的乳腺发育。此外，它们突出了瘦素在生命早期关键营养窗口期对长期生长和乳腺功能可能发挥的重要调节作用。
