scholarly journals Food intake dependent and independent effects of heat stress on lactation and mammary gland development

2020 ◽  
Author(s):  
Yao Xiao ◽  
Jason M. Kronenfeld ◽  
Benjamin J. Renquist

ABSTRACTWith a growing population, a reliable food supply is increasingly important. Heat stress reduces livestock meat and milk production. Genetic selection of high producing animals increases endogenous heat production, while climate change increases exogenous heat exposure. Both sources of heat exacerbate the risk of heat-induced depression of production. Rodents are valuable models to understand mechanisms conserved across species. Heat exposure suppresses feed intake across homeothermic species including rodents and production animal species. We assessed the response to early-mid lactation or late gestation heat exposure on milk production and mammary gland development/function, respectively. Using pair-fed controls we experimentally isolated the food intake dependent and independent effects of heat stress on mammary function and mass. Heat exposure (35°C, relative humidity 50%) decreased daily food intake. When heat exposure occurred during lactation, hypophagia accounted for approximately 50% of the heat stress induced hypogalactia. Heat exposure during middle to late gestation suppressed food intake, which was fully responsible for the lowered mammary gland weight of dams at parturition. However, the impaired mammary gland function in heat exposed dams measured by metabolic rate and lactogenesis could not be explained by depressed food consumption. In conclusion, mice recapitulate the depressed milk production and mammary gland development observed in dairy species while providing insight regarding the role of food intake. This opens the potential to apply genetic, experimental and pharmacological models unique to mice to identify the mechanism by which heat is limiting animal production.Summary StatementsThis study demonstrates that heat stress decreases lactation and mammary development through food intake dependent and independent mechanisms.

2009 ◽  
Vol 29 (16) ◽  
pp. 4455-4466 ◽  
Author(s):  
Sarah M. Francis ◽  
Jacqueline Bergsied ◽  
Christian E. Isaac ◽  
Courtney H. Coschi ◽  
Alison L. Martens ◽  
...  

ABSTRACT Transforming growth factor β (TGF-β) is a crucial mediator of breast development, and loss of TGF-β-induced growth arrest is a hallmark of breast cancer. TGF-β has been shown to inhibit cyclin-dependent kinase (CDK) activity, which leads to the accumulation of hypophosphorylated pRB. However, unlike other components of TGF-β cytostatic signaling, pRB is thought to be dispensable for mammary development. Using gene-targeted mice carrying subtle missense changes in pRB (Rb1 ΔL and Rb1NF ), we have discovered that pRB plays a critical role in mammary gland development. In particular, Rb1 mutant female mice have hyperplastic mammary epithelium and defects in nursing due to insensitivity to TGF-β growth inhibition. In contrast with previous studies that highlighted the inhibition of cyclin/CDK activity by TGF-β signaling, our experiments revealed that active transcriptional repression of E2F target genes by pRB downstream of CDKs is also a key component of TGF-β cytostatic signaling. Taken together, our work demonstrates a unique functional connection between pRB and TGF-β in growth control and mammary gland development.


2020 ◽  
Vol 103 (9) ◽  
pp. 8576-8586
Author(s):  
Thiago F. Fabris ◽  
Jimena Laporta ◽  
Amy L. Skibiel ◽  
Bethany Dado-Senn ◽  
Stephanie E. Wohlgemuth ◽  
...  

Endocrinology ◽  
2008 ◽  
Vol 150 (3) ◽  
pp. 1485-1494 ◽  
Author(s):  
Mark D. Aupperlee ◽  
Alexis A. Drolet ◽  
Srinivasan Durairaj ◽  
Weizhong Wang ◽  
Richard C. Schwartz ◽  
...  

Progesterone (P) is required for normal mammary gland development, and is implicated in the etiology of mammary cancer in rodents and humans. We analyzed mammary gland developmental responses to P and estrogen (E) in two strains of mice (BALB/c and C57BL/6) that exhibit differences in ductal development at sexual maturity and alveologenesis during pregnancy. C57BL/6 mice exhibited reduced proliferative and morphological responses to P. Analysis of known mediators of sidebranching and alveologenesis revealed that reduced P-induced expression of P receptor isoform B and receptor activator of nuclear factor-κB ligand (RANKL), as well as altered expression and regulation of cyclin D1, CCAAT/enhancer binding protein β, and the downstream effectors of RANKL, nuclear Id2 and p21, contribute significantly to the reduced P responsiveness of the C57BL/6 mammary gland. In contrast, E responsiveness was greater in C57BL/6 than in BALB/c glands. E may play a compensatory role in C57BL/6 alveologenesis through its effect on the induction and activation of signal transducer and activator of transcription 5a, a known regulator of RANKL. These observations suggest that in human populations with heterogeneous genetic backgrounds, individuals may respond differentially to the same hormone. Thus, genetic diversity may have a role in determining the effects of P in normal mammary development and tumorigenesis. Reduced progesterone-induced expression of progesterone receptor and RANKL, altered expression and regulation of C/EBPβ, and of the downstream effectors of RANKL, nuclear Id2 and p21, contribute significantly to the reduced progesterone-responsiveness of the C57BL/6 mammary gland compared to the BALB/c gland.


2020 ◽  
Author(s):  
Rong Xuan ◽  
Tianle Chao ◽  
Xiaodong Zhao ◽  
Aili Wang ◽  
Yunpeng Chu ◽  
...  

Abstract Background From the late lactation to late gestation stages, the mammary gland tissue of goats undergoes a process from involution to remodeling and then to high differentiation of mammary gland tissue. From the perspective of lactation, this is a continuous development process of the goat mammary gland from the termination of lactation to the restoration of lactation. We performed transcriptome sequencing on goat mammary gland tissues at three mammary gland developmental stages to screen for differentially expressed genes that affect mammary gland development and the physiological process of lactation and mapped their expression profiles in three stages. The objective of this study is to reveal the expression characteristics of these genes and their potential function during mammary gland development and lactation. Results We identified 1,381 differentially expressed genes in the mammary gland during three stages and found that the expression level of genes encoding casein, such as alpha-s1-casein (CSN1S1), alpha-s2-casein (CSN1S2), beta-casein (CSN2), and kappa-casein (CSN3), and alpha-lactalbumin (LALBA) were higher in mammary gland tissues during the late lactation stage and late gestation stage than those during the dry period. In addition, we constructed six functional networks related to differentially expressed genes and found that these genes are closely related to mammary gland growth and development, apoptosis, immunity, substance transport, biosynthesis, and metabolism. Finally, we identified 35 differentially expressed transcription factors, which were classified into 16 families, and predicted that transcription factors of the basic leucine zipper domain (bZIP) family and basic helix-loop-helix (bHLH) family regulated the expression levels of genes related to mammary gland development and lactation. Conclusions Among the late lactation, dry period, and late gestation stages, there are differences in the expression levels of genes related to mammary gland growth and development, apoptosis, immunity, basic substance transport, biosynthesis, and metabolism in mammary gland tissues. Some genes in the same family or with similar functions have similar expression patterns. These differentially expressed genes or transcription factors work synergistically to participate in the regulation of mammary gland development and the physiological process of lactation.


Author(s):  
Weizhen Chen ◽  
Wei Wei ◽  
Liya Yu ◽  
Xin Zhang ◽  
Fujing Huang ◽  
...  

Baicalin, the main flavonoid component extracted from Scutellaria roots, has a variety of biological activities and is therefore used in the treatment of many kinds of diseases. However, whether baicalin affects the normal development of tissues and organs is still unclear. Here, using a mouse mammary gland model, we investigated the effects of baicalin on the expansion of mammary stem cells (MaSCs) and mammary development, as well as breast cancer progression. Interestingly, we found that baicalin administration significantly accelerates duct elongation at puberty, and promotes alveolar development and facilitates milk secretion during pregnancy. Furthermore, self-renewal of MaSCs was significantly promoted in the presence of baicalin. Moreover, in a tumor xenograft model, baicalin promoted tumor growth of the MDA-MB-231 cell line, but suppressed tumor growth of the ZR-751 cell line. Mechanistically, baicalin can induce expression of the protein C receptor, while inhibiting the expression of the estrogen receptor. Transcriptome analysis revealed that baicalin is involved in signaling pathways related to mammary gland development, immune response, and cell cycle control. Taken together, our results from comprehensive investigation of the biological activity of baicalin provide a theoretical basis for its rational clinical application.


2009 ◽  
Vol 21 (4) ◽  
pp. 549 ◽  
Author(s):  
Laura J. Parry ◽  
Lenka A. Vodstrcil ◽  
Anna Madden ◽  
Stephanie H. Amir ◽  
Katrina Baldwin ◽  
...  

Pups born to mice with a targeted deletion of relaxin or its receptor (Rxfp1) die within 24 h postpartum. This has been attributed, in part, to abnormal mammary gland development in relaxin-mutant mice (Rln–/–). However, mammary development is normal in relaxin receptor-mutant (Rxfp1–/–) mice. The present study aimed to verify the mammary phenotypes in late pregnant and early lactating Rln–/– mice and to test the hypothesis that relaxin is involved in milk protein synthesis. Comparisons between late pregnant and early lactating wildtype (Rln+/+) and Rln–/– mice showed no differences in lobuloalveolar structure or ductal branching in the mammary gland. Mammary explants from Rln–/– mice also expressed β-casein and α-lactalbumin in response to lactogenic hormones at a similar level to Rln+/+ mice, implying normal milk protein synthesis. Pregnant Rln–/– mice infused with relaxin for 6 days gave birth to live pups without difficulty, and 96% of pups survived beyond 7 days. This is in contrast with the 100% pup mortality in saline-treated Rln–/– mice or 3-day relaxin-treated Rln–/– mice. Pups born to relaxin-treated Rln–/– dams weighed significantly less than Rln+/+ pups but had similar growth rates as their wildtype counterparts. In summary, relaxin is not critical for mammary gland development or β-casein and α-lactalbumin expression in late pregnant mice. In addition, Rln–/– dams did not need to be treated with relaxin postpartum for the pups to survive, suggesting that relaxin has no role in the maintenance of lactation in mice.


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