Milk is synthesized by mammary epithelial cells of lactating mammals. The synthetic capacity of the mammary gland depends largely on the number and efficiency of functional mammary epithelial cells. Structural develop...Milk is synthesized by mammary epithelial cells of lactating mammals. The synthetic capacity of the mammary gland depends largely on the number and efficiency of functional mammary epithelial cells. Structural development of the mammary gland occurs during fetal growth, prepubertal and post-pubertal periods, pregnancy, and lactation under the control of various hormones （particularly estrogen, growth hormone, insulin-like growth factor-I, progesterone, placental lactogen, and prolactin） in a species- and stage-dependent manner. Milk is essential for the growth, development, and health of neonates. Amino acids （AA）, present in both free and peptide-bound forms, are the most abundant organic nutrients in the milk of farm animals. Uptake of AA from the arterial blood of the lactating dam is the ultimate source of proteins （primarily 13-casein and a-lactalbumin） and bioactive nitrogenous metabolites in milk. Results of recent studies indicate extensive catabolism of branched-chain AA （leucine, isoleucine and valine） and arginine to synthesize glutamate, glutamine, alanine, aspartate, asparagine, proline, and polyamines. The formation of polypeptides from AA is regulated not only by hormones （e.g., prolactin, insulin and glucocorticoids） and the rate of blood flow across the lactating mammary gland, but also by concentrations of AA, lipids, glucose, vitamins and minerals in the maternal plasma, as well as the activation of the mechanistic （mammalian） target rapamycin signaling by certain AA （e.g., arginine, branched-chain AA, and glutamine）. Knowledge of AA utilization （including metabolism） by mammary epithelial cells will enhance our fundamental understanding of lactation biology and has important implications for improving the efficiency of livestock production worldwide.展开更多
Hypoxia is a physiological or pathological condition of a deficiency of oxygen supply in the body as a whole or within a tissue. During hypoxia, tissues undergo a series of physiological responses to defend themselves...Hypoxia is a physiological or pathological condition of a deficiency of oxygen supply in the body as a whole or within a tissue. During hypoxia, tissues undergo a series of physiological responses to defend themselves against a low oxygen supply, including increased angiogenesis, erythropoiesis, and glucose uptake. The effects of hypoxia are mainly mediated by hypoxia-inducible factor 1 （HIF-1）, which is a heterodimeric transcription factor consisting of o and 13 subunits. HIF-1β is constantly expressed, whereas HIF-1α is degraded under normal oxygen conditions. Hypoxia stabilizes HIF-1α and the HIF complex, and HIF then translocates into the nucleus to initiate the expression of target genes. Hypoxia has been extensively studied for its role in promoting tumor progression, and emerging evidence also indicates that hypoxia may play important roles in physiological processes, including mammary development and lactation. The mammary gland exhibits an increasing metabolic rate from pregnancy to lactation to support mammary growth, lactogenesis, and lactation. This process requires increasing amounts of oxygen consumption and results in localized chronic hypoxia as confirmed by the binding of the hypoxia marker pimonidazole HCI in mouse mammary gland. We hypothesized that this hypoxic condition promotes mammary development and lactation, a hypothesis that is supported by the following several lines of evidence： i） Mice with an HIF-1α deletion selective for the mammary gland have impaired mammary differentiation and lipid secretion, resulting in lactation failure and striking changes in milk compositions; ii） We recently observed that hypoxia significantly induces HIF-1α- dependent glucose uptake and GLUT1 expression in mammary epithelial cells, which may be responsible for the dramatic increases in glucose uptake and GLUT1 expression in the mammary gland during the transition period from late pregnancy to early lactation; and iii） Hypoxia and HIF-1α increase the phosphorylation of signal transducers展开更多
The mammary gland is a dynamic organ that undergoes significant changes at multiple stages of postnatal development.Although the roles of systemic hormones and microenvironmental cues in mammary homeostasis have been ...The mammary gland is a dynamic organ that undergoes significant changes at multiple stages of postnatal development.Although the roles of systemic hormones and microenvironmental cues in mammary homeostasis have been extensively studied,the influence of neural signals,particularly those from the sympathetic nervous system,remains poorly understood.Here,using a mouse mammary gland model,we delved into the regulatory role of sympathetic nervous signaling in the context of mammary stem cells and mammary development.Our findings revealed that depletion of sympathetic nerve signals results in defective mammary development during puberty,adulthood,and pregnancy,accompanied by a reduction in mammary stem cell numbers.Through in vitro three-dimensional culture and in vivo transplantation analyses,we demonstrated that the absence of sympathetic nerve signals hinders mammary stem cell self-renewal and regeneration,while activation of sympathetic nervous signaling promotes these capacities.Mechanistically,sympathetic nerve signals orchestrate mammary stem cell activity and mammary development through the extracellular signal-regulated kinase signaling pathway.Collectively,our study unveils the crucial roles of sympathetic nerve signals in sustaining mammary development and regulating mammary stem cell activity,offering a novel perspective on the involvement of the nervous system in modulating adult stem cell function and organ development.展开更多
Lauric acid(LA)has the possibility to improve milk production in dairy cows by improving mammary gland development,however,the mechanism by which it might regulate mammary gland development is unclear.The influence of...Lauric acid(LA)has the possibility to improve milk production in dairy cows by improving mammary gland development,however,the mechanism by which it might regulate mammary gland development is unclear.The influence of LA on milk production,nutrient digestibility and the expression of proteins related to mammary gland development in dairy cows were evaluated.Forty primiparous Holstein dairy cows were divided into 4 groups in a randomized block design.Four treatments included the control(0 g/d LA per cow),low-LA(100 g/d LA per cow),medium-LA(200 g/d LA per cow),and high-LA(300 g/d LA per cow).Yields of milk,fat-corrected milk,and energy-corrected milk quadratically increased(P<0.05),and yield and content of milk fat linearly increased(P<0.05)with LA supplementation.Percentages of C12:0,C18:1 and C20:1 fatty acids in milk fat linearly increased(P<0.05),but that of C16:0 fatty acid linearly decreased(P=0.046).Supplementation of LA led to a linear and quadratical increase(P<0.05)in digestibility of dry matter,organic matter,neutral detergent fibre and acid detergent fibre,and ruminal total volatile fatty acid concentration but a linear reduction(P=0.018)in the ratio of acetate to propionate.The enzymatic activities of ruminal pectinase,xylanase,andα-amylase,and populations of total bacteria and anaerobic fungi increased linearly(P<0.05),while populations of total protozoa and methanogens decreased linearly(P<0.05)with increased LA addition.Following LA addition,blood glucose,triglyceride,estradiol,prolactin,and insulin-like growth factor 1 concentrations increased linearly(P<0.05)and albumin and total protein concentrations increased quadratically(P<0.05).Moreover,addition of 200 g/d LA promoted(P<0.05)the expression of protein involved in mammary gland development and fatty acids synthesis.These results suggested that LA addition enhanced milk production and fatty acids synthesis by stimulating nutrient digestion,the expression of proteins associated with milk fat synthesis and mammary gland development.展开更多
This experiment was to evaluate the influence of sodium butyrate(SB)addition on milk production,ruminal fermentation,nutrient digestion,and the development and metabolism regulation of the mammary gland in dairy cows....This experiment was to evaluate the influence of sodium butyrate(SB)addition on milk production,ruminal fermentation,nutrient digestion,and the development and metabolism regulation of the mammary gland in dairy cows.Forty Holstein dairy cows averaging 710±18.5 kg body weight,72.8±3.66 d in milk(DIM),and 41.4±1.42 kg/d milk production were divided into four treatments blocked by DIM and milk production.Treatments were control group,low SB,medium SB,and high SB with 0,100,200 and 300 g/d of SB addition per cow,respectively.The study lasted for 105 d.Production of milk,milk protein and lactose quadratically increased(P<0.05),while fat-corrected milk,energycorrected milk and milk fat yields linearly increased(P<0.05)with increasing SB addition.The digestibility of dietary dry matter,organic matter,and crude protein linearly increased(P<0.05),whereas the digestibility of ether extract,neutral detergent fibre,and acid detergent fibre quadratically increased(P<0.05).Ruminal pH quadratically decreased(P=0.04),while total volatile fatty acids(VFA)quadratically increased(P=0.03)with increasing SB addition.The acetic acid to propionic acid ratio increased(P=0.03)linearly due to the unaltered acetic acid molar percentage and a linear decrease in propionic acid molar percentage.Ruminal enzymatic activity of carboxymethyl-cellulase and a-amylase,populations of total bacteria,total anaerobic fungi,total protozoa,Ruminococcus albus,R.flavefaciens,Butyrivibrio fibrisolvens,Fibrobacter succinogenes,and Ruminobacter amylophilus linearly increased(P<0.05).Blood glucose,urea nitrogen,and non-esterified fatty acids linearly decreased(P<0.05),while total protein concentration linearly increased(P=0.04).Moreover,the addition of SB at 200 g/d promoted(P<0.05)mRNA and protein expression of PPARγ,SREBF1,ACACA,FASN,SCD,CCNA2,CCND1,PCNA,Bcl-2,GPR41,and the ratios of p-Akt/Akt and p-mTOR/mTOR,but decreased(P<0.05)mRNA and protein expressions of Bax,caspase-3,and caspase-9.The results suggest that milk production and milk fat synthesis in展开更多
Breast cancer incidence has increased and become the world’s most prevalent cancer,which is related to abnormal development of mammary glands and thought to be influenced by environment endocrine disruptors such as b...Breast cancer incidence has increased and become the world’s most prevalent cancer,which is related to abnormal development of mammary glands and thought to be influenced by environment endocrine disruptors such as bisphenol A(BPA).However,whether its substitution,bisphenol B(BPB),has similar effects remains a concern.In the present study,a maternal exposure model of ICR mice combined time-series RNA-seq analysis was established to explore the underlying correlation among maternal BPB exposure(300μg/kg body weight),mammary gland development,and long-term breast health in offspring.The results showed that BPB exposure disrupted hormonal homeostasis of the female offspring but did not affect the branch development of mammary glands in a time-dependent manner.However,at postnatal day 90(PND90),BPB exposure resulted in duct dilatation,lobular hyperplasia,and inflammatory cell infiltration and increased the number of hormone receptor-expressing(HR+)luminal cells in offspring.Further,the differentially expressed genes in time-series analysis of RNA-seq for mammary glands of the female offspring were enriched in the morphogenesis of branching structures,branching epithelium,and branching morphogenesis of epithelial tubes,which are always considered gland development.Interestingly,the results of RNA-seq also suggested that progesterone receptor(Pgr)mRNA expression in the BPB group was elevated at PND90,and breast cancer related genes such as GATA binding protein 3(Gata3)and epidermal growth factor receptor(Egfr)were also altered.These findings suggested that maternal BPB exposure did not accelerate mammary gland development or lead to obvious morphological anomalies of offspring,but it induced pathological changes and altered cancer related gene expression in adult offspring breast.展开更多
基金supported by Texas A&M Agri Life Research (H-8200)The Agriculture and Food Research Initiative Competitive Grant from the Animal Growth & Nutrient Utilization Program of the USDA National Institute of Food and Agriculture (2014-67015-21770)+4 种基金National Basic Research Program of China (2012CB126305)National Natural Science Foundation of China (31572412 and 31272450)the 111 Project (B16044)Natural Science Foundation of Hubei Province (2013CFA097 and 2013CFB325)Hubei Hundred Talent program
文摘Milk is synthesized by mammary epithelial cells of lactating mammals. The synthetic capacity of the mammary gland depends largely on the number and efficiency of functional mammary epithelial cells. Structural development of the mammary gland occurs during fetal growth, prepubertal and post-pubertal periods, pregnancy, and lactation under the control of various hormones （particularly estrogen, growth hormone, insulin-like growth factor-I, progesterone, placental lactogen, and prolactin） in a species- and stage-dependent manner. Milk is essential for the growth, development, and health of neonates. Amino acids （AA）, present in both free and peptide-bound forms, are the most abundant organic nutrients in the milk of farm animals. Uptake of AA from the arterial blood of the lactating dam is the ultimate source of proteins （primarily 13-casein and a-lactalbumin） and bioactive nitrogenous metabolites in milk. Results of recent studies indicate extensive catabolism of branched-chain AA （leucine, isoleucine and valine） and arginine to synthesize glutamate, glutamine, alanine, aspartate, asparagine, proline, and polyamines. The formation of polypeptides from AA is regulated not only by hormones （e.g., prolactin, insulin and glucocorticoids） and the rate of blood flow across the lactating mammary gland, but also by concentrations of AA, lipids, glucose, vitamins and minerals in the maternal plasma, as well as the activation of the mechanistic （mammalian） target rapamycin signaling by certain AA （e.g., arginine, branched-chain AA, and glutamine）. Knowledge of AA utilization （including metabolism） by mammary epithelial cells will enhance our fundamental understanding of lactation biology and has important implications for improving the efficiency of livestock production worldwide.
基金supported by National Research Initiative Competitive grant 2007-35206-18037 from the USDA National Institute of Food and Agriculture(to FQZ)
文摘Hypoxia is a physiological or pathological condition of a deficiency of oxygen supply in the body as a whole or within a tissue. During hypoxia, tissues undergo a series of physiological responses to defend themselves against a low oxygen supply, including increased angiogenesis, erythropoiesis, and glucose uptake. The effects of hypoxia are mainly mediated by hypoxia-inducible factor 1 （HIF-1）, which is a heterodimeric transcription factor consisting of o and 13 subunits. HIF-1β is constantly expressed, whereas HIF-1α is degraded under normal oxygen conditions. Hypoxia stabilizes HIF-1α and the HIF complex, and HIF then translocates into the nucleus to initiate the expression of target genes. Hypoxia has been extensively studied for its role in promoting tumor progression, and emerging evidence also indicates that hypoxia may play important roles in physiological processes, including mammary development and lactation. The mammary gland exhibits an increasing metabolic rate from pregnancy to lactation to support mammary growth, lactogenesis, and lactation. This process requires increasing amounts of oxygen consumption and results in localized chronic hypoxia as confirmed by the binding of the hypoxia marker pimonidazole HCI in mouse mammary gland. We hypothesized that this hypoxic condition promotes mammary development and lactation, a hypothesis that is supported by the following several lines of evidence： i） Mice with an HIF-1α deletion selective for the mammary gland have impaired mammary differentiation and lipid secretion, resulting in lactation failure and striking changes in milk compositions; ii） We recently observed that hypoxia significantly induces HIF-1α- dependent glucose uptake and GLUT1 expression in mammary epithelial cells, which may be responsible for the dramatic increases in glucose uptake and GLUT1 expression in the mammary gland during the transition period from late pregnancy to early lactation; and iii） Hypoxia and HIF-1α increase the phosphorylation of signal transducers
基金This work was supported by grants from the Ministry of Science and Technology of China(National Program on Key Basic Research Project:2019YFA0802804 to L.Y.)the National Natural Science Foundation of China(31871492 and 32270837 to C.C.)+1 种基金Hubei Provincial Natural Science Foundation(2023AFB784 to Y.X.)the Fundamental Research Funds for the Central Universities(2042022kf1146 to Y.X.and 2042022dx0003).
文摘The mammary gland is a dynamic organ that undergoes significant changes at multiple stages of postnatal development.Although the roles of systemic hormones and microenvironmental cues in mammary homeostasis have been extensively studied,the influence of neural signals,particularly those from the sympathetic nervous system,remains poorly understood.Here,using a mouse mammary gland model,we delved into the regulatory role of sympathetic nervous signaling in the context of mammary stem cells and mammary development.Our findings revealed that depletion of sympathetic nerve signals results in defective mammary development during puberty,adulthood,and pregnancy,accompanied by a reduction in mammary stem cell numbers.Through in vitro three-dimensional culture and in vivo transplantation analyses,we demonstrated that the absence of sympathetic nerve signals hinders mammary stem cell self-renewal and regeneration,while activation of sympathetic nervous signaling promotes these capacities.Mechanistically,sympathetic nerve signals orchestrate mammary stem cell activity and mammary development through the extracellular signal-regulated kinase signaling pathway.Collectively,our study unveils the crucial roles of sympathetic nerve signals in sustaining mammary development and regulating mammary stem cell activity,offering a novel perspective on the involvement of the nervous system in modulating adult stem cell function and organ development.
基金funded by the Education Department of Shanxi Province,Excellent Doctor Work Award Fund Research Project[SXYBKY2018036]Modern Agro industry Technology Research System of Shanxi Province (2023CYJSTX13).
文摘Lauric acid(LA)has the possibility to improve milk production in dairy cows by improving mammary gland development,however,the mechanism by which it might regulate mammary gland development is unclear.The influence of LA on milk production,nutrient digestibility and the expression of proteins related to mammary gland development in dairy cows were evaluated.Forty primiparous Holstein dairy cows were divided into 4 groups in a randomized block design.Four treatments included the control(0 g/d LA per cow),low-LA(100 g/d LA per cow),medium-LA(200 g/d LA per cow),and high-LA(300 g/d LA per cow).Yields of milk,fat-corrected milk,and energy-corrected milk quadratically increased(P<0.05),and yield and content of milk fat linearly increased(P<0.05)with LA supplementation.Percentages of C12:0,C18:1 and C20:1 fatty acids in milk fat linearly increased(P<0.05),but that of C16:0 fatty acid linearly decreased(P=0.046).Supplementation of LA led to a linear and quadratical increase(P<0.05)in digestibility of dry matter,organic matter,neutral detergent fibre and acid detergent fibre,and ruminal total volatile fatty acid concentration but a linear reduction(P=0.018)in the ratio of acetate to propionate.The enzymatic activities of ruminal pectinase,xylanase,andα-amylase,and populations of total bacteria and anaerobic fungi increased linearly(P<0.05),while populations of total protozoa and methanogens decreased linearly(P<0.05)with increased LA addition.Following LA addition,blood glucose,triglyceride,estradiol,prolactin,and insulin-like growth factor 1 concentrations increased linearly(P<0.05)and albumin and total protein concentrations increased quadratically(P<0.05).Moreover,addition of 200 g/d LA promoted(P<0.05)the expression of protein involved in mammary gland development and fatty acids synthesis.These results suggested that LA addition enhanced milk production and fatty acids synthesis by stimulating nutrient digestion,the expression of proteins associated with milk fat synthesis and mammary gland development.
基金This work was funded by Education Department of Shanxi Province(Grant no.SXYBKY2018036)the Animal Husbandry‘1331 project’Key Discipline Construction Special Project of Shanxi Province.
文摘This experiment was to evaluate the influence of sodium butyrate(SB)addition on milk production,ruminal fermentation,nutrient digestion,and the development and metabolism regulation of the mammary gland in dairy cows.Forty Holstein dairy cows averaging 710±18.5 kg body weight,72.8±3.66 d in milk(DIM),and 41.4±1.42 kg/d milk production were divided into four treatments blocked by DIM and milk production.Treatments were control group,low SB,medium SB,and high SB with 0,100,200 and 300 g/d of SB addition per cow,respectively.The study lasted for 105 d.Production of milk,milk protein and lactose quadratically increased(P<0.05),while fat-corrected milk,energycorrected milk and milk fat yields linearly increased(P<0.05)with increasing SB addition.The digestibility of dietary dry matter,organic matter,and crude protein linearly increased(P<0.05),whereas the digestibility of ether extract,neutral detergent fibre,and acid detergent fibre quadratically increased(P<0.05).Ruminal pH quadratically decreased(P=0.04),while total volatile fatty acids(VFA)quadratically increased(P=0.03)with increasing SB addition.The acetic acid to propionic acid ratio increased(P=0.03)linearly due to the unaltered acetic acid molar percentage and a linear decrease in propionic acid molar percentage.Ruminal enzymatic activity of carboxymethyl-cellulase and a-amylase,populations of total bacteria,total anaerobic fungi,total protozoa,Ruminococcus albus,R.flavefaciens,Butyrivibrio fibrisolvens,Fibrobacter succinogenes,and Ruminobacter amylophilus linearly increased(P<0.05).Blood glucose,urea nitrogen,and non-esterified fatty acids linearly decreased(P<0.05),while total protein concentration linearly increased(P=0.04).Moreover,the addition of SB at 200 g/d promoted(P<0.05)mRNA and protein expression of PPARγ,SREBF1,ACACA,FASN,SCD,CCNA2,CCND1,PCNA,Bcl-2,GPR41,and the ratios of p-Akt/Akt and p-mTOR/mTOR,but decreased(P<0.05)mRNA and protein expressions of Bax,caspase-3,and caspase-9.The results suggest that milk production and milk fat synthesis in
基金supported by National Science Foundation of China(Nos.22106098,21906099,and 22036005)Youth Science and Technology Research Foundation of Shanxi Province(20210302124298)+2 种基金Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(2020L0174)Startup Foundation for Doctors of Shanxi Province(SD1917)Startup Foundation for Doctors of Shanxi Medical University(XD1917).
文摘Breast cancer incidence has increased and become the world’s most prevalent cancer,which is related to abnormal development of mammary glands and thought to be influenced by environment endocrine disruptors such as bisphenol A(BPA).However,whether its substitution,bisphenol B(BPB),has similar effects remains a concern.In the present study,a maternal exposure model of ICR mice combined time-series RNA-seq analysis was established to explore the underlying correlation among maternal BPB exposure(300μg/kg body weight),mammary gland development,and long-term breast health in offspring.The results showed that BPB exposure disrupted hormonal homeostasis of the female offspring but did not affect the branch development of mammary glands in a time-dependent manner.However,at postnatal day 90(PND90),BPB exposure resulted in duct dilatation,lobular hyperplasia,and inflammatory cell infiltration and increased the number of hormone receptor-expressing(HR+)luminal cells in offspring.Further,the differentially expressed genes in time-series analysis of RNA-seq for mammary glands of the female offspring were enriched in the morphogenesis of branching structures,branching epithelium,and branching morphogenesis of epithelial tubes,which are always considered gland development.Interestingly,the results of RNA-seq also suggested that progesterone receptor(Pgr)mRNA expression in the BPB group was elevated at PND90,and breast cancer related genes such as GATA binding protein 3(Gata3)and epidermal growth factor receptor(Egfr)were also altered.These findings suggested that maternal BPB exposure did not accelerate mammary gland development or lead to obvious morphological anomalies of offspring,but it induced pathological changes and altered cancer related gene expression in adult offspring breast.
