PMID- 35346464 OWN - NLM STAT- MEDLINE DCOM- 20220517 LR - 20220531 IS - 1525-3198 (Electronic) IS - 0022-0302 (Linking) VI - 105 IP - 6 DP - 2022 Jun TI - Transcriptome profiling of the nonlactating mammary glands of dairy goats reveals the molecular genetic mechanism of mammary cell remodeling. PG - 5238-5260 LID - S0022-0302(22)00183-7 [pii] LID - 10.3168/jds.2021-21039 [doi] AB - 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 G(1)/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. CI - (c) 2022, The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association(R). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). FAU - Xuan, Rong AU - Xuan R AD - College of Animal Science and Veterinary Medicine, Shandong Agricultural University, 271018, Tai'an, Shandong Province, P.R. China. FAU - Chao, Tianle AU - Chao T AD - College of Animal Science and Veterinary Medicine, Shandong Agricultural University, 271018, Tai'an, Shandong Province, P.R. China. FAU - Zhao, Xiaodong AU - Zhao X AD - College of Animal Science and Veterinary Medicine, Shandong Agricultural University, 271018, Tai'an, Shandong Province, P.R. China. FAU - Wang, Aili AU - Wang A AD - College of Animal Science and Veterinary Medicine, Shandong Agricultural University, 271018, Tai'an, Shandong Province, P.R. China. FAU - Chu, Yunpeng AU - Chu Y AD - College of Animal Science and Veterinary Medicine, Shandong Agricultural University, 271018, Tai'an, Shandong Province, P.R. China. FAU - Li, Qing AU - Li Q AD - College of Animal Science and Veterinary Medicine, Shandong Agricultural University, 271018, Tai'an, Shandong Province, P.R. China. FAU - Zhao, Yilin AU - Zhao Y AD - College of Animal Science and Veterinary Medicine, Shandong Agricultural University, 271018, Tai'an, Shandong Province, P.R. China. FAU - Ji, Zhibin AU - Ji Z AD - College of Animal Science and Veterinary Medicine, Shandong Agricultural University, 271018, Tai'an, Shandong Province, P.R. China. FAU - Wang, Jianmin AU - Wang J AD - College of Animal Science and Veterinary Medicine, Shandong Agricultural University, 271018, Tai'an, Shandong Province, P.R. China. Electronic address: wangjm@sdau.edu.cn. LA - eng PT - Journal Article DEP - 20220326 PL - United States TA - J Dairy Sci JT - Journal of dairy science JID - 2985126R SB - IM MH - Animals MH - Female MH - Gene Expression Profiling/veterinary MH - Goats/genetics MH - Lactation/genetics MH - *Mammary Glands, Animal/metabolism MH - *Phosphatidylinositol 3-Kinases/metabolism MH - Pregnancy OTO - NOTNLM OT - dairy goat OT - late gestation OT - late lactation OT - mammary gland involution OT - the dry period EDAT- 2022/03/30 06:00 MHDA- 2022/05/18 06:00 CRDT- 2022/03/29 05:41 PHST- 2021/07/20 00:00 [received] PHST- 2022/01/12 00:00 [accepted] PHST- 2022/03/30 06:00 [pubmed] PHST- 2022/05/18 06:00 [medline] PHST- 2022/03/29 05:41 [entrez] AID - S0022-0302(22)00183-7 [pii] AID - 10.3168/jds.2021-21039 [doi] PST - ppublish SO - J Dairy Sci. 2022 Jun;105(6):5238-5260. doi: 10.3168/jds.2021-21039. Epub 2022 Mar 26.