Abstract：
The mammary gland redevelops to the prepregnancy state during involution, which shows the mammary cells have the characteristics of remodeling. The rapidity and degree of mammary gland involution vary across species (e.g., between model organism mice and dairy livestock). However, the molecular genetic mechanism of involution and remodeling of goat mammary gland has not yet been clarified. This work investigated the structural changes and transcriptome characteristics of the mammary gland tissue of nonlactating dairy goats during the late lactation (LL), the dry period (DP), and late gestation (LG). Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining revealed significant changes in the structure of the nonlactating goat mammary gland, and obvious cell apoptosis occurred at LL and DP. Sequencing identified 1,381 genes that are differentially expressed in mammary gland tissue at the 3 developmental stages. Genes related to cell growth, apoptosis, immunity, nutrient transport, synthesis, and metabolism exhibited adaptive transcriptional changes to meet the needs of a new set of mammary gland lactation functions. The significant enrichment of Gene Ontology terms such as humoral immune response, complement activation, and neutrophil-mediated immunity indicates that the innate immune system plays an important role in maintaining the health of degenerative mammary glands and eliminating apoptotic cells. The peroxisome proliferator-activated receptor signaling pathway plays an important regulatory role in lipid metabolism, especially the adaptive changes in expression of genes encoded lipid transport and enzymes, which promote the formation of milk fat during the lactation. The mammary gland development gene module revealed that pregnancy hormone receptors, cell growth factors and their receptors, and genes encoding insulin-like growth factor binding proteins regulate the physiological process of mammary gland involution through adaptive transcriptional changes. Interestingly, ERBB4 was identified as the hub gene of the network that regulates mammary gland growth and development. Overexpression of ERBB4 in mammary epithelial cells cultured in vitro can reduce cell cycle arrest in G1/S phase and apoptosis by regulating the PI3K/Akt signaling pathway and promote the proliferation of mammary epithelial cells. The gene ERBB4 also affects the expression of genes that initiate mammary gland involution and promote mammary gland remodeling. These findings contribute to an in-depth understanding of the molecular mechanisms involved in mammary gland involution and remodeling.
摘要：
在退化期间乳腺重新发育到孕前状态，这表明乳腺细胞具有重塑的特征。乳腺退化的速度和程度因物种而异(例如，在模型生物小鼠和乳牛之间)。然而,山羊乳腺退化和重塑的分子遗传机制尚未阐明。这项工作研究了泌乳后期（LL）非泌乳奶山羊乳腺组织的结构变化和转录组特征，干旱期(DP)，妊娠晚期（LG）。末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）染色显示非泌乳山羊乳腺的结构发生了显着变化，LL和DP发生明显的细胞凋亡。测序鉴定了在3个发育阶段在乳腺组织中差异表达的1,381个基因。与细胞生长有关的基因，凋亡，豁免权,养分运输，合成，和代谢表现出适应性转录变化，以满足一组新的乳腺泌乳功能的需求。体液免疫应答等基因本体术语的显著丰富,补体激活,和中性粒细胞介导的免疫表明，先天免疫系统在维持变性乳腺的健康和消除凋亡细胞中起着重要作用。过氧化物酶体增殖物激活受体信号通路在脂质代谢中起着重要的调节作用,特别是编码脂质转运和酶的基因表达的适应性变化，在哺乳期促进乳脂的形成。乳腺发育基因模块揭示了妊娠激素受体，细胞生长因子及其受体，和编码胰岛素样生长因子结合蛋白的基因通过适应性转录变化调节乳腺退化的生理过程。有趣的是,ERBB4被鉴定为调节乳腺生长和发育的网络的中心基因。在体外培养的乳腺上皮细胞中过表达ERBB4可通过调节PI3K/Akt信号通路减少细胞周期停滞在G1/S期和凋亡，促进乳腺上皮细胞的增殖。ERBB4基因还影响启动乳腺退化和促进乳腺重塑的基因的表达。这些发现有助于深入了解乳腺退化和重塑的分子机制。
