scholarly journals Photoperiod effects on milk production in goats: Are they mediated by the molecular clock in the mammary gland?

2014 ◽  
Author(s):  
Therese Casey ◽  
Sameer J. Mabjeesh ◽  
Avi Shamay ◽  
Karen Plaut
Keyword(s):  
Growth Rate ◽  
Mammary Gland ◽  
Epithelial Cell ◽  
Milk Production ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial Cells ◽  
Physiological State ◽  
Mammary Development ◽  
Mammary Epithelial ◽  
Protein Levels

US scientists, Dr. Theresa Casey and Dr. Karen Plaut, collaborated with Israeli scientists, Dr. SameerMabjeesh and Dr. AviShamay to conduct studies proposed in the BARD Project No. US-4715-14 Photoperiod effects on milk production in goats: Are they mediated by the molecular clock in the mammary gland over the last 3 years. CLOCK and BMAL1 are core components of the circadian clock and as heterodimers function as a transcription factor to drive circadian-rhythms of gene expression. Studies of CLOCK-mutant mice found impaired mammary development in late pregnancy was related to poor lactation performance post-partum. To gain a better understanding of role of clock in regulation of mammary development studies were conducted with the mammary epithelial cell line HC11. Decreasing CLOCK protein levels using shRNA resulted in increased mammary epithelial cell growth rate and impaired differentiation, with lower expression of differentiation markers including ad herens junction protein and fatty acid synthesis genes. When BMAL1 was knocked out using CRISPR-CAS mammary epithelial cells had greater growth rate, but reached stationary phase at a lower density, with FACS indicating cells were growing and dying at a faster rate. Beta-casein milk protein levels were significantly decreased in BMAL1 knockout cells. ChIP-seq analysis was conducted to identify BMAL1 target genes in mammary epithelial cells. Studies conducted in goats found that photoperiod duration and physiological state affected the dynamics of the mammary clock. Effects were likely independent of the photoperiod effects on prolactin levels. Interestingly, circadian rhythms of core body temperature, which functions as a key synchronizing cue sent out by the central clock in the hypothalamus, were profoundly affected by photoperiod and physiological state. Data support that the clock in the mammary gland regulates genes important to development of the gland and milk synthesis. We also found the clock in the mammary is responsive to changes in physiological state and photoperiod, and thus may serve as a mechanism to establish milk production levels in response to environmental cues. 

Nulliparous CCAAT/Enhancer Binding Proteinδ (C/EBPδ) Knockout Mice Exhibit Mammary Gland Ductal Hyperlasia

2003 ◽  
Vol 228 (3) ◽  
pp. 278-285 ◽  
Author(s):  
Andrew P. Gigliotti ◽  
Peter F. Johnson ◽  
Esta Sterneck ◽  
James W. DeWille
Keyword(s):  
Mammary Gland ◽  
Cell Growth ◽  
Epithelial Cell ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial Cells ◽  
Growth Control ◽  
Mammary Epithelial ◽  
Estrus Cycle ◽  
The Mean ◽  
Cell Growth Control

CCAAT/Enhancer binding proteins (C/EBPs) are a family of nuclear proteins that function in the control of cell growth, death, and differentiation. We previously reported that C/EBPδ plays a key role in mammary epithelial cell G0 growth arrest. In this report, we investigated the role of C/EBPδ in mammary gland development and function using female mice homozygous for a targeted deletion of C/EBPδ (C/EBPδ –/–). C/EBPδ –/– females develop normally and exhibit normal reproductive and lactational performance. Adult nulliparous C/EBPδ –/– females, however, exhibit mammary epithelial cell growth control defects. The mean number of mammary ductal branches is significantly higher in adult nulliparous C/EBPδ –/– females compared with C/EBPδ +/+ (wild-type control) females (66.8 ± 5.2 vs 42.9 * 6.3 branch points/field, P < 0.01). In addition, the mean total mammary gland cellular volume occupied by epithelium is significantly higher in adult nulliparous C/EBPδ –/– females compared with C/EBPδ +/+ controls (29.0± 1.4 vs 20.4 ± 1.3, P < 0.001). Our results showed that the BrdU labeling index was significantly higher in mammary epithelial cells from nulliparous C/EBPδ –/– females compared with C/EBPδ +/+ controls during the proestrus/estrus (4.55 ± 0.70 vs 2.14 ± 0.43, P < 0.01) and metestrus/diestrus (6.92 ± 0.75 vs 3.98 ± 0.43 P < 0.01) phases of the estrus cycle. In contrast, the percentage of mammary epithelial cells undergoing apoptosis during both phases of the estrus cycle did not differ between C/EBPδ –/– and C/EBPδ +/+ females. The increased epithelial cell content and proliferative capacity was restricted to the nulliparous C/EBPδ –/– females as no differences in mammary gland morphology, ductal branching or total epithelial content were observed between multiparous C/EBPδ –/– and C/EBPδ +/+ females. These results demonstrate that C/EBPδ plays a novel role in mammary epithelial cell growth control that appears to be restricted to the nulliparous mammary gland.

scholarly journals Oestradiol enhances apoptosis in bovine mammary epithelial cells in vitro

2012 ◽  
Vol 80 (1) ◽  
pp. 113-121 ◽  
Author(s):  
Lucile Yart ◽  
Laurence Finot ◽  
Vanessa Lollivier ◽  
Frederic Dessauge
Keyword(s):  
Mammary Gland ◽  
Milk Production ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial Cells ◽  
Major Effect ◽  
Mammary Epithelial ◽  
Bovine Mammary Epithelial Cells ◽  
Lactating Mammary Gland ◽  
Negative Effect

Ovarian steroids, oestradiol and progesterone, are required for normal mammary growth at puberty and during pregnancy. They contribute to mammary parenchyma development by stimulating mammary epithelial cell (MEC) proliferation. However several studies demonstrate that oestradiol negatively affects milk production during the declining phase of lactation, but the oestradiol effect on MEC in lactating mammary gland remains unclear. The objective of this study was to investigate the differential effect of oestradiol on bovine MECs mimicking two physiological statuses: active and early apoptotic MECs. We demonstrated that oestradiol has a major effect on early apoptotic MECs and might accelerate MEC apoptosis by activation of caspases rather than by inducing apoptosis in active MECs. Early apoptotic MECs could be compared with senescent cells in the late-lactation mammary gland. These results suggest that the negative effect of oestradiol on milk production during the declining phase of lactation would be due to an enhancement of apoptotic processes in MECs.

Zip3 plays a major role in zinc uptake into mammary epithelial cells and is regulated by prolactin

2005 ◽  
Vol 288 (5) ◽  
pp. C1042-C1047 ◽  
Author(s):  
Shannon L. Kelleher ◽  
Bo Lönnerdal
Keyword(s):  
Mammary Gland ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial Cells ◽  
Cell Model ◽  
Mammary Epithelial ◽  
Maternal Circulation ◽  
Physiological Explanation ◽  
Secretory Phenotype

During lactation, a substantial amount of Zn2+ is transferred by the mammary gland from the maternal circulation into milk; thus secretory mammary epithelial cells must tightly regulate Zn2+ transport to ensure optimal Zn2+ transfer to the suckling neonate. To date, six Zn2+ import proteins (Zip1–6) have been identified; however, Zip3 expression is restricted to tissues with unique requirements for Zn2+, such as the mammary gland, which suggests that it may play a specialized role in this tissue. In the present study, we have used a unique mammary epithelial cell model (HC11) to characterize the role of Zip3 in mammary epithelial cell Zn2+ transport. Confocal microscopy demonstrated that Zip3 is localized to the cell surface in mammary epithelial cells and transiently relocalized to an intracellular compartment in cells with a secretory phenotype. Total 65Zn transport was higher in secreting cells, while gene silencing of Zip3 decreased 65Zn uptake into mammary epithelial cells, particularly in those with a secretory phenotype. Finally, reduced expression of Zip3 ultimately resulted in cell death, indicating that mammary epithelial cells have a unique requirement for Zip3-mediated Zn2+ import, which may reflect the unique requirement for Zn2+ of this highly specialized cell type and thus provides a physiological explanation for the restricted tissue distribution of this Zn2+ importer.

scholarly journals A Novel Pathway for Mammary Epithelial Cell Invasion Induced by the Helix-Loop-Helix Protein Id-1

1998 ◽  
Vol 18 (8) ◽  
pp. 4577-4588 ◽  
Author(s):  
Pierre-Yves Desprez ◽  
Claudia Qiao Lin ◽  
Nicole Thomasset ◽  
Carolyn J. Sympson ◽  
Mina J. Bissell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Epithelial Cell ◽  
Basement Membrane ◽  
Human Breast Cancer ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Human Breast ◽  
Helix Loop Helix

ABSTRACT Mammary epithelial cells undergo changes in growth, invasion, and differentiation throughout much of adulthood, and most strikingly during pregnancy, lactation, and involution. Although the pathways of milk protein expression are being elucidated, little is known, at a molecular level, about control of mammary epithelial cell phenotypes during normal tissue morphogenesis and evolution of aggressive breast cancer. We developed a murine mammary epithelial cell line, SCp2, that arrests growth and functionally differentiates in response to a basement membrane and lactogenic hormones. In these cells, expression of Id-1, an inhibitor of basic helix-loop-helix transcription factors, declines prior to differentiation, and constitutive Id-1 expression blocks differentiation. Here, we show that SCp2 cells that constitutively express Id-1 slowly invade the basement membrane but remain anchorage dependent for growth and do not form tumors in nude mice. Cells expressing Id-1 secreted a ∼120-kDa gelatinase. From inhibitor studies, this gelatinase appeared to be a metalloproteinase, and it was the only metalloproteinase detectable in conditioned medium from these cells. A nontoxic inhibitor diminished the activity of this metalloproteinase in vitro and repressed the invasive phenotype of Id-1-expressing cells in culture. The implications of these findings for normal mammary-gland development and human breast cancer were investigated. A gelatinase of ∼120 kDa was expressed by the mammary gland during involution, a time when Id-1 expression is high and there is extensive tissue remodeling. Moreover, high levels of Id-1 expression and the activity of a ∼120-kDa gelatinase correlated with a less-differentiated and more-aggressive phenotype in human breast cancer cells. We suggest that Id-1 controls invasion by normal and neoplastic mammary epithelial cells, primarily through induction of a ∼120-kDa gelatinase. This Id-1-regulated invasive phenotype could contribute to involution of the mammary gland and possibly to the development of invasive breast cancer.

MicroRNA-432 inhibits milk fat synthesis by targeting SCD and LPL in ovine mammary epithelial cells

2021 ◽  
Author(s):  
Zhiyun Hao ◽  
Yuzhu Luo ◽  
Jiqing Wang ◽  
Jon Hickford ◽  
Huitong Zhou ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Milk Production ◽  
Milk Fat ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Differentially Expressed ◽  
Differentially Expressed Mirnas ◽  
Fat Synthesis ◽  
Milk Fat Synthesis

In our previous studies, microRNA-432 (miR-432) was found to be one of differentially expressed miRNAs in ovine mammary gland between the two breeds of lactating sheep with different milk production...

scholarly journals Chemerin Regulates Epithelial Barrier Function of Mammary Glands in Dairy Cows

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3194
Author(s):  
Yutaka Suzuki ◽  
Sachi Chiba ◽  
Koki Nishihara ◽  
Keiichi Nakajima ◽  
Akihiko Hagino ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Dairy Cows ◽  
Barrier Function ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Epithelial Barrier ◽  
Epithelial Tissue ◽  
Epithelial Barrier Function

Epithelial barrier function in the mammary gland acts as a forefront of the defense mechanism against mastitis, which is widespread and a major disorder in dairy production. Chemerin is a chemoattractant protein with potent antimicrobial ability, but its role in the mammary gland remains unelucidated. The aim of this study was to determine the function of chemerin in mammary epithelial tissue of dairy cows in lactation or dry-off periods. Mammary epithelial cells produced chemerin protein, and secreted chemerin was detected in milk samples. Chemerin treatment promoted the proliferation of cultured bovine mammary epithelial cells and protected the integrity of the epithelial cell layer from hydrogen peroxide (H2O2)-induced damage. Meanwhile, chemerin levels were higher in mammary tissue with mastitis. Tumor necrosis factor alpha (TNF-α) strongly upregulated the expression of the chemerin-coding gene (RARRES2) in mammary epithelial cells. Therefore, chemerin was suggested to support mammary epithelial cell growth and epithelial barrier function and to be regulated by inflammatory stimuli. Our results may indicate chemerin as a novel therapeutic target for diseases in the bovine mammary gland.

scholarly journals Loss of vitamin D receptor signaling from the mammary epithelium or adipose tissue alters pubertal glandular development

2014 ◽  
Vol 307 (8) ◽  
pp. E674-E685 ◽  
Author(s):  
Abby L. Johnson ◽  
Glendon M. Zinser ◽  
Susan E. Waltz
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Mammary Gland ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Mammary Epithelium ◽  
Mammary Development ◽  
Mammary Epithelial ◽  
Cell Type ◽  
Pubertal Mammary Development

Vitamin D3 receptor (VDR) signaling within the mammary gland regulates various postnatal stages of glandular development, including puberty, pregnancy, involution, and tumorigenesis. Previous studies have shown that vitamin D3 treatment induces cell-autonomous growth inhibition and differentiation of mammary epithelial cells in culture. Furthermore, mammary adipose tissue serves as a depot for vitamin D3 storage, and both epithelial cells and adipocytes are capable of bioactivating vitamin D3. Despite the pervasiveness of VDR in mammary tissue, individual contributions of epithelial cells and adipocytes, as well as the VDR-regulated cross-talk between these two cell types during pubertal mammary development, have yet to be investigated. To assess the cell-type specific effect of VDR signaling during pubertal mammary development, novel mouse models with mammary epithelial- or adipocyte-specific loss of VDR were generated. Interestingly, loss of VDR in either cellular compartment accelerated ductal morphogenesis with increased epithelial cell proliferation and decreased apoptosis within terminal end buds. Conversely, VDR signaling specifically in the mammary epithelium modulated hormone-induced alveolar growth, as ablation of VDR in this cell type resulted in precocious alveolar development. In examining cellular cross-talk ex vivo, we show that ligand-dependent VDR signaling in adipocytes significantly inhibits mammary epithelial cell growth in part through the vitamin D3-dependent production of the cytokine IL-6. Collectively, these studies delineate independent roles for vitamin D3-dependent VDR signaling in mammary adipocytes and epithelial cells in controlling pubertal mammary gland development.

Mammary gland copper transport is stimulated by prolactin through alterations in Ctr1 and Atp7A localization

2006 ◽  
Vol 291 (4) ◽  
pp. R1181-R1191 ◽  
Author(s):  
Shannon L. Kelleher ◽  
Bo Lönnerdal
Keyword(s):  
Plasma Membrane ◽  
Mammary Gland ◽  
Molecular Mechanisms ◽  
Mammary Epithelial Cells ◽  
Milk Composition ◽  
Mammary Epithelial ◽  
Recycling Endosome ◽  
Protein Levels ◽  
Stage Of Lactation ◽  
Golgi Network

Milk copper (Cu) concentration declines and directly reflects the stage of lactation. Three Cu-specific transporters (Ctr1, Atp7A, Atp7B) have been identified in the mammary gland; however, the integrated role they play in milk Cu secretion is not understood. Whereas the regulation of milk composition by the lactogenic hormone prolactin (PRL) has been documented, the specific contribution of PRL to this process is largely unknown. Using the lactating rat as a model, we determined that the normal decline in milk Cu concentration parallels declining Cu availability to the mammary gland and is associated with decreased Atp7B protein levels. Mammary gland Cu transport was highest during early lactation and was stimulated by suckling and hyperprolactinemia, which was associated with Ctr1 and Atp7A localization at the plasma membrane. Using cultured mammary epithelial cells (HC11), we demonstrated that Ctr1 stains in association with intracellular vesicles that partially colocalize with transferrin receptor (recycling endosome marker). Atp7A was primarily colocalized with mannose 6-phosphate receptor (M6PR; late endosome marker), whereas Atp7B was partially colocalized with protein disulfide isomerase (endoplasmic reticulum marker), TGN38 ( trans-Golgi network marker) and M6PR. Prolactin stimulated Cu transport as a result of increased Ctr1 and Atp7A abundance at the plasma membrane. Although the molecular mechanisms responsible for these posttranslational changes are not understood, transient changes in prolactin signaling play a role in the regulation of mammary gland Cu secretion during lactation.

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