Epigenetic Regulation of Milk Production in Dairy Cows

  • Kuljeet Singh
  • Richard A. Erdman
  • Kara M. Swanson
  • Adrian J. Molenaar
  • Nauman J. Maqbool
  • Thomas T. Wheeler
  • Juan A. Arias
  • Erin C. Quinn-Walsh
  • Kerst Stelwagen


It is well established that milk production of the dairy cow is a function of mammary epithelial cell (MEC) number and activity and that these factors can be influenced by diverse environmental influences and management practises (nutrition, milk frequency, photoperiod, udder health, hormonal and local effectors). Thus, understanding how the mammary gland is able to respond to these environmental cues provides a huge potential to enhance milk production of the dairy cow. In recent years our understanding of molecular events within the MEC underlying bovine lactation has been advanced through mammary microarray studies and will be further advanced through the recent availability of the bovine genome sequence. In addition, the potential of epigenetic regulation (non-sequence inheritable chemical changes in chromatin, such as DNA methylation and histone modifications, which affect gene expression) to manipulate mammary function is emerging. We propose that a substantial proportion of unexplained phenotypic variation in the dairy cow is due to epigenetic regulation. Heritability of epigenetic marks also highlights the potential to modify lactation performance of offspring. Understanding the response of the MEC (cell signaling pathways and epigenetic mechanisms) to external stimuli will be an important prerequisite to devising new technologies for maximising their activity and, hence, milk production in the dairy cow.


Bovine Mammary gland Epigenetic regulation Milk production 



Composite response elements




Extra-cellular matrix


Kilo base pairs


Mammary epithelial cell(s)


Signal transducer and activator of transcription



The authors wish to acknowledge financial support from the New Zealand Foundation for Research, Science and Technology.


  1. 1.
    Tucker HA. Factors affecting mammary gland cell numbers. J Dairy Sci. 1969;52(5):720–9.PubMedGoogle Scholar
  2. 2.
    Sinha YN, Tucker HA. Mammary development and pituitary prolactin level of heifers from birth through puberty and during estrus cycle. J Dairy Sci. 1969;52(4):507–12.PubMedGoogle Scholar
  3. 3.
    Anderson RR, Harness JR, Snead AF, Salah MS. Mammary growth pattern in goats during pregnancy and lactation. J Dairy Sci. 1981;64(3):427–32.PubMedCrossRefGoogle Scholar
  4. 4.
    Anderson RR. Mammary gland growth in sheep. J Anim Sci. 1975;41(1):118–23.PubMedGoogle Scholar
  5. 5.
    Finucane KA, McFadden TB, Bond JP, Kennelly JJ, Zhao FQ. Onset of lactation in the bovine mammary gland: gene expression profiling indicates a strong inhibition of gene expression in cell proliferation. Funct Integr Genomics. 2008;8(3):251–64.PubMedGoogle Scholar
  6. 6.
    Knight CH, Wide CJ. Mammary growth during lactation: implications for increasing milk yield. J Dairy Sci. 1987;70(9):1991–2000.PubMedCrossRefGoogle Scholar
  7. 7.
    Capuco AV, Akers RM, Smith JJ. Mammary growth in Holstein cows during the dry period: quantification of nucleic acids and histology. J Dairy Sci. 1997;80(3):477–87.PubMedCrossRefGoogle Scholar
  8. 8.
    Neville MC, Peaker M. Ionized calcium in milk and the integrity of the mammary epithelium in the goat. J Physiol Lond. 1981;313(1):561–70.PubMedGoogle Scholar
  9. 9.
    Stelwagen K, Davis SR, Farr VC, Prosser CG, Sherlock RA. Mammary epithelial cell tight junction integrity and mammary blood flow during an extended milking interval in goats. J Dairy Sci. 1994;77(2):426–32.PubMedCrossRefGoogle Scholar
  10. 10.
    Stelwagen K, Farr VC, Davis SR, Prosser CG. EGTA-induced disruption of epithelial cell tight junctions in the lactating caprine mammary gland. Am J Physiol. 1995;269(4):R848–55.PubMedGoogle Scholar
  11. 11.
    Singh K, Dobson J, Phyn CVC, Davis SR, Farr VC, Molenaar AJ, et al. Milk accumulation decreases expression of genes involved in cell-extracellular matrix communication and is associated with induction of apoptosis in the bovine mammary gland. Livest Prod Sci. 2005;98(1–2):67–78.Google Scholar
  12. 12.
    Suchyta SP, Sipkovsky S, Halgren RG, Kruska R, Elftman M, Weber-Nielsen M, et al. Bovine mammary gene expression profiling using cDNA microarray enhanced for mammary-specific transcripts. Physiol Genomics. 2003;16(1):8–18.PubMedGoogle Scholar
  13. 13.
    Singh K, Davis SR, Dobson J, Molenaar AJ, Wheeler T, Prosser C, et al. cDNA microarray analysis reveals antioxidant and immune genes are up-regulated during involution of the bovine mammary gland. J Dairy Sci. 2008;91(6):2236–46.PubMedGoogle Scholar
  14. 14.
    Conner EE, Siferd S, Elsasser TH, Evock-Clover CM, Van Tassell CP, Sonstegard TS, et al. Effect of increased milking frequency on gene expression in the bovine mammary gland. BMC Genomics. 2008;9:362.Google Scholar
  15. 15.
    Elsik CG, Tellam RL, Worley KC, Gibbs RA, Muzny DM, et al. The genome sequence of taurine cattle: a window to ruminant biology and evolution. Science. 2009;324(5926):522–8.PubMedGoogle Scholar
  16. 16.
    Lemay DG, Lynn DJ, Martin WF, Neville MC, Casey TM, Rincon G, et al. The bovine lactation genome: insights into the evolution of mammalian milk. Genome Biol. 2009;10(4):R43.PubMedGoogle Scholar
  17. 17.
    Tellam RL, Lemay DG, Van Tassell CP, Lewin HA, Worley KC, Elsik CG. Unlocking the bovine genome. BMC Genomics. 2009;10:193.PubMedGoogle Scholar
  18. 18.
    Sejrsen K, Purup S. Influence of prepubertal feeding level on milk yield potential of dairy heifers: a review. J Anim Sci. 1997;75(3):828–35.PubMedGoogle Scholar
  19. 19.
    Petitclerc D, Kineman RD, Zinn SA, Tucker HA. Mammary growth response of Holstein heifers to photoperiod. J Dairy Sci. 1985;68(1):86–90.PubMedCrossRefGoogle Scholar
  20. 20.
    Chase LE. Developing nutrition programs for high producing dairy herds. J Dairy Sci. 1993;76(10):3287–93.PubMedCrossRefGoogle Scholar
  21. 21.
    Dahl GE, Petitclerc D. Management of photoperiod in the dairy herd for improved production and health. J Anim Sci. 2003;81(Supplement 3):11–7.PubMedGoogle Scholar
  22. 22.
    Stelwagen K. Effect of milking frequency on mammary function and shape of the lactation curve. J Dairy Sci. 2001;84(E-supplement):E204–11.CrossRefGoogle Scholar
  23. 23.
    Erdman RA, Varner M. Fixed yield responses to increased milking frequency. J Dairy Sci. 1995;78(5):1199–203.PubMedCrossRefGoogle Scholar
  24. 24.
    Bauman DE, Eppard PJ, DeGeeter MJ, Lanza GM. Responses of high-producing dairy cows to long-term treatment with pituitary somatotropin and recombinant somatotropin. J Dairy Sci. 1985;68(6):1352–62.PubMedCrossRefGoogle Scholar
  25. 25.
    Peel CJ, Bauman DE. Somatotropin and lactation. J Dairy Sci. 1987;70(2):474–86.PubMedCrossRefGoogle Scholar
  26. 26.
    King JO. Cell counts and composition of bovine milk. Vet Rec. 1978;103(18):397–8.PubMedGoogle Scholar
  27. 27.
    Meijering A, Jaartsveld FH, Verstegen MW, Tielen MJ. The cell count of milk in relation to milk yield. J Dairy Res. 1978;45(1):5–14.PubMedGoogle Scholar
  28. 28.
    Raubertas RF, Shook GE. Relationship between lactation measures of somatic cell concentration and milk yield. J Dairy Sci. 1982;65(3):419–25.CrossRefGoogle Scholar
  29. 29.
    Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16(1):6–21.PubMedGoogle Scholar
  30. 30.
    Rosen JM, Matusik RJ, Richards DA, Gupta P, Rodgers JR. Multihormonal regulation of casein gene expression at the transcriptional and posttranscriptional levels in the mammary gland. Recent Prog Horm Res. 1980;36:57–92.Google Scholar
  31. 31.
    Ramsahoye BH, Biniszkiewicz D, Lyko F, Clark V, Bird AP, Jaenisch R. Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. Proc Nat Acad Sci USA. 2000;97(10):5237–42.PubMedGoogle Scholar
  32. 32.
    Vanselow J, Yang W, Herrmann J, Zerbe H, Schuberth H-J, Petzl W, et al. DNA-remethylation around a STAT5-binding enhancer in the far distal αS1-casein promoter is associated with abrupt shut-down of αS1-casein synthesis during acute mastitis. J Mol Endocrinol. 2006;37(3):463–77.PubMedGoogle Scholar
  33. 33.
    Kangaspeska S, Stride B, Métivier R, Polycarpou-Schwarz M, Ibberson D, Carmouche RP, et al. Transient cyclical methylation of promoter DNA. Nature. 2008;452(7183):112–5.PubMedGoogle Scholar
  34. 34.
    Métivier R, Gallais R, Tiffoche C, Le Péron C, Jurkowska RZ, Carmouche RP, et al. Cyclical DNA methylation of a transcriptionally active promoter. Nature. 2008;452(7183):45–50.PubMedGoogle Scholar
  35. 35.
    Molenaar A, Seyfert H-M, Swanson K, Stelwagen K, Singh K. Compaction of the alpha-S1-casein and opening of a defensin promoter occurs during S. uberis infection of the bovine mammary gland. Proc QMB conference; 2009.Google Scholar
  36. 36.
    Schmitt-Ney M, Happ B, Hofer P, Hynes NE, Groner B. Mammary gland-specific nuclear factor activity is positively regulated by lactogenic hormones and negatively by milk stasis. Mol Endocrinol. 1992;6(12):988–97.Google Scholar
  37. 37.
    Wakao H, Schmitt-Ney M, Groner B. Mammary gland-specific nuclear factor is present in lactating rodent and bovine mammary tissue and composed of a single polypeptide of 89 kDa. J Biol Chem. 1992;267(23):16365–70.PubMedGoogle Scholar
  38. 38.
    Wakao H, Gouilleux F, Groner B. Mammary gland factor (MGF) is a novel member of the cytokine regulated transcription factor gene family and confers the prolactin response. EMBO J. 1995;14(4):854–5.PubMedGoogle Scholar
  39. 39.
    Liu X, Robinson GW, Gouilleux F, Groner B, Hennighausen L. Cloning and expression of Stat5 and an additional homologue (Stat5b) involved in prolactin signal transduction in mouse mammary tissue. Proc Nat Acad Sci USA. 1995;92(19):8831–5.PubMedGoogle Scholar
  40. 40.
    Gouilleux F, Wakao H, Mundt M, Groner B. Prolactin induces phosphorylation of Tyr694 of Stat5 (MGF), a prerequisite for DNA binding and induction of transcription. EMBO J. 1994;13(18):4361–9.PubMedGoogle Scholar
  41. 41.
    Liu X, Robinson GW, Hennighausen L. Activation of Stat5a and Stat5b by tyrosine phosphorylation is tightly linked to mammary gland differentiation. Mol Endocrinol. 1996;10(12):1496–506.PubMedGoogle Scholar
  42. 42.
    Liu X, Robinson GW, Wagner KU, Garrett L, Wynshaw-Boris A, Hennighausen L. Stat5a is mandatory for adult mammary gland development and lactogenesis. Genes Dev. 1997;11(2):179–86.PubMedGoogle Scholar
  43. 43.
    Teglund S, McKay C, Schuetz E, van Deursen JM, Stravopodis D, Wang D, et al. Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell. 1998;93(5):841–50.PubMedGoogle Scholar
  44. 44.
    Juergens WG, Stockdale FE, Topper YJ, Elias JJ. Hormone-dependent differentiation of mammary gland in vitro. Proc Nat Acad Sci USA. 1965;54(2):629–34.PubMedGoogle Scholar
  45. 45.
    Guyette WA, Matusik RJ, Rosen JM. Prolactin-mediated transcriptional and posttranscriptional control of casein gene expression. Cell. 1979;17(4):1013–23.PubMedGoogle Scholar
  46. 46.
    Hennighausen L, Robinson GW, Wagner K-U, Liu X. Prolactin signaling in mammary gland development. J Biol Chem. 1997;272(12):7567–9.PubMedGoogle Scholar
  47. 47.
    Yu-Lee L-Y, Luo G, Book ML, Morris SM. Lactogenic hormone signal transduction. Biol Reprod. 1998;58(2):295–301.PubMedGoogle Scholar
  48. 48.
    Groner B. Transcription factor regulation in mammary epithelial cells. Domest Anim Endocrinol. 2002;23(1–2):25–32.PubMedGoogle Scholar
  49. 49.
    Watson CJ, Burdon TG. Prolactin signal transduction mechanisms in the mammary gland: the role of the Jak/Stat pathway. Rev Reprod. 1996;1(1):1–5.PubMedGoogle Scholar
  50. 50.
    Jahn GA, Daniel N, Jolivet G, Belair L, Bole-Feysot C, Kelly PA, et al. In vivo study of prolactin (PRL) intracellular signalling during lactogenesis in the rat: JAK/STAT pathway is activated by PRL in the mammary gland but not in the liver. Biol Reprod. 1997;57(4):894–900.PubMedGoogle Scholar
  51. 51.
    Schindler U, Wu P, Rothe M, Brasseur M, McKnight SL. Components of a Stat recognition code: evidence for two layers of molecular specificity. Immunity. 1995;2(6):689–97.PubMedGoogle Scholar
  52. 52.
    Ehret GB, Reichenbach P, Schindler U, Horvath CM, Fritz S, Nabholz M, et al. DNA binding specificity of different STAT proteins. Comparison of in vitro specificity with natural target sites. J Biol Chem. 2001;276(9):6675–88.PubMedGoogle Scholar
  53. 53.
    Demmer J, Burdon TG, Djiane J, Watson CJ, Clark AJ. The proximal milk protein binding factor binding site is required for the prolactin responsiveness of the sheep beta-lactoglobulin promoter in Chinese hamster ovary cells. Mol Cell Endocrinol. 1995;107(1):113–21.PubMedGoogle Scholar
  54. 54.
    Rosen JM, Wyszomierski SL, Hadsell D. Regulation of milk protein gene expression. Annu Rev Nutr. 1999;19:407–36.PubMedGoogle Scholar
  55. 55.
    Mukhopadhyay SS, Wyszomierski SL, Gronostajski RM, Rosen JM. Differential interactions of specific nuclear factor I isoforms with the glucocorticoid receptor and STAT5 in the cooperative regulation of WAP gene transcription. Mol Cell Biol. 2001;21(20):6859–69.PubMedGoogle Scholar
  56. 56.
    Wyszomierski SL, Rosen JM. Cooperative effects of STAT5 (signal transducer and activator of transcription 5) and C/EBP b (CCAAT/enhancer-binding protein-b) on b-casein gene transcription are mediated by the glucocorticoid receptor. Mol Endocrinol. 2001;15(2):228–40.PubMedGoogle Scholar
  57. 57.
    Ovcharenko I, Loots GG, Giardine BM, Hou M, Ma J, Hardison RC, et al. Mulan: multiple-sequence local alignment and visualization for studying function and evolution. Genome Res. 2005;15(1):184–94.PubMedGoogle Scholar
  58. 58.
    Winklehner-Jennewein P, Geymayer S, Lechner J, Welte T, Hansson L, Geley S, et al. A distal enhancer region in the human b-casein gene mediates the response to prolactin and glucocorticoid hormones. Gene. 1998;218(1–2):127–39.Google Scholar
  59. 59.
    Rijnkels M, Kooiman PM, Platenburg GJ, van Dixhoorn M, Nuijens JH, De Boer HA, et al. High-level expression of bovine alpha s1-casein in milk of transgenic mice. Transgenic Res. 1998;7(1):5–14.PubMedGoogle Scholar
  60. 60.
    Jolivet G, L’Hotte C, Pierre S, Tourkine N, Houdebine L-M. A MGF/STAT5 binding site is necessary in the distal enhancer for high prolactin induction of transfected rabbit as1-casein-CAT gene transcription. FEBS Lett. 1996;389(3):257–62.PubMedGoogle Scholar
  61. 61.
    Pantano T, Jolivet G, Prince S, Menck-Le BC, Maeder C, Viglietta C, et al. Effect of the rabbit alpha s1-casein gene distal enhancer on the expression of a reporter gene in vitro and in vivo. Biochem Biophys Res Commun. 2002;290(1):53–61.PubMedGoogle Scholar
  62. 62.
    Pfitzner E, Jahne R, Wissler M, Stoecklin E, Groner B. p300/CREB-binding protein enhances the prolactin-mediated transcriptional induction through direct interaction with the transactivating domain of Stat5, but does not participate in the Stat5-mediated suppression of the glucocorticoid response. Mol Endocrinol. 1998;12(10):1582–93.PubMedGoogle Scholar
  63. 63.
    Litterst CM, Kliem S, Marilley D, Pfitzner E. NCoA-1/SRC-1 is an essential coactivator of STAT5 that binds to the FDL motif in the {alpha}-helical region of the STAT5 transactivation domain. J Biol Chem. 2003;278(46):45340–51.PubMedGoogle Scholar
  64. 64.
    Gardiner-Garden M, Frommer M. CpG islands in vertebrate genomes. J Mol Biol. 1987;196(2):261–82.PubMedGoogle Scholar
  65. 65.
    Takai D, Jones PA. Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc Nat Acad Sci. 2002;99(6):3740–5.PubMedGoogle Scholar
  66. 66.
    Singh K, Swanson K, Couldrey C, Seyfert H-M, Stelwagen K. Suppression of bovine αS1-casein gene expression during involution of the mammary gland is associated with increased DNA methylation at a STAT5-binding site in the αS1-casein promoter. J Dairy Sci. 2008;91(E-Suppl 1):378.Google Scholar
  67. 67.
    Singh K, Swanson K, Couldrey C, Seyfert H-M, Stelwagen K. DNA methylation events associated with the suppression of milk protein gene expression during involution of the bovine mammary gland. Proc NZ Soc Anim Prod. 2009;69:57–9.Google Scholar
  68. 68.
    Capuco AV, Wood DL, Baldwin R, Mcleod K, Paape MJ. Mammary cell number, proliferation, and apoptosis during a bovine lactation: relation to milk production and effect of bST. J Dairy Sci. 2001;84(10):2177–87.PubMedCrossRefGoogle Scholar
  69. 69.
    Goodman RE, Schanbacher FL. Bovine lactoferrin mRNA: sequence, analysis, and expression in the mammary gland. Biochem Biophys Res Commun. 1991;180(1):75–84.PubMedGoogle Scholar
  70. 70.
    Wilde CJ, Addey CVP, Li P, Fernig DG. Programmed cell death in bovine mammary tissue during lactation and involution. Exp Physiol. 1997;82(5):943–53.PubMedGoogle Scholar
  71. 71.
    Holst BD, Hurley WL, Nelson DR. Involution of the bovine mammary gland: histological and ultrastructural changes. J Dairy Sci. 1987;70(5):935–44.PubMedCrossRefGoogle Scholar
  72. 72.
    Kritikou EA, Sharkey A, Abell K, Came PJ, Anderson E, Clarkson RW, et al. A dual, non-redundant, role for LIF as a regulator of development and STAT3-mediated cell death in mammary gland. Development. 2003;130(15):3459–6.PubMedGoogle Scholar
  73. 73.
    Swanson KM, Stelwagen K, Dobson J, Henderson HV, Davis SR, Farr VC, et al. Transcriptome profiling of Streptococcus uberis-induced mastitis reveals fundamental differences between immune gene expression in the mammary gland and in a primary cell culture model. J Dairy Sci. 2009;92(1):117–2.PubMedGoogle Scholar
  74. 74.
    Long E, Capuco AV, Wood DL, Sonstegard T, Tomita G, Paape MJ, et al. Escherichia coli induces apoptosis and proliferation of mammary cells. Cell Death Differ. 2001;8(8):808–16.PubMedGoogle Scholar
  75. 75.
    Singh K, Vetharaniam I, Prewitz M, Dobson J, Stelwagen K. Leukaemia inhibitory factor signalling during the switch from lactation to involution. Proc NZ Soc Anim Prod. 2009;69:65–7.Google Scholar
  76. 76.
    Davis SR, Farr VC, Stelwagen K. Regulation of yield loss and milk composition during once-daily milking: a review. Livest Prod Sci. 1999;59(1):77–94.Google Scholar
  77. 77.
    Hurley WL. Mammary gland function during involution. J Dairy Sci. 1989;72(6):1637–46.PubMedCrossRefGoogle Scholar
  78. 78.
    Swanson KM, Stelwagen K, Singh K. Epigenetic regulation of milk protein expression in the bovine mammary gland during extended involution. Proc QMB conference; 2009.Google Scholar
  79. 79.
    Lelièvre SA, Weaver VM, Nickerson JA, Larabell CA, Bhaumik A, Petersen OW, et al. Tissue phenotype depends on reciprocal interactions between the extracellular matrix and the structural organization of the nucleus. Proc Natl Acad Sci USA. 1998;95(25):14711–6.PubMedGoogle Scholar
  80. 80.
    Pujuguet P, Radisky D, Levy D, Lacza C, Bissell MJ. Trichostatin A inhibits beta-casein expression in mammary epithelial cells. J Cell Biochem. 2001;83(4):660–70.PubMedGoogle Scholar
  81. 81.
    Le Beyec J, Xu R, Lee SY, Nelson CM, Rizki A, Alcaraz J, et al. Cell shape regulates global histone acetylation in human mammary epithelial cells. Exp Cell Res. 2007;313(14):3066–75.PubMedGoogle Scholar
  82. 82.
    Xu R, Nelson CM, Muschler JL, Veiseh M, Vonderhaar BK, Bissell MJ. Sustained activation of STAT5 is essential for chromatin remodeling and maintenance of mammary-specific function. Cell Biol. 2009;184(1):57–66.Google Scholar
  83. 83.
    Jolivet G, Pantano T, Houdebine LM. Regulation by the extracellular matrix (ECM) of prolactin-induced alpha s1-casein gene expression in rabbit primary mammary cells: role of STAT5, C/EBP, and chromatin structure. Cell Biochem. 2005;95(2):313–27.Google Scholar
  84. 84.
    Kabotyanski EB, Huetter M, Xian W, Rijnkels M, Rosen JM. Integration of prolactin and glucocorticoid signaling at the beta-casein promoter and enhancer by ordered recruitment of specific transcription factors and chromatin modifiers. Mol Endocrinol. 2006;20(10):2355–68.PubMedGoogle Scholar
  85. 85.
    Green KA, Streuli CH. Apoptosis regulation in the mammary gland. Cell Mol Life Sci. 2004;61(15):1867–83.PubMedGoogle Scholar
  86. 86.
    Ford Jr JA, Park CS. Nutritionally directed compensatory growth enhances heifer development and lactation potential. J Dairy Sci. 2001;84(7):1669–78.PubMedCrossRefGoogle Scholar
  87. 87.
    Park CS, Baik MG, Keller WL, Berg IE, Erickson GM. Role of compensatory growth in lactation: a stair-step nutrient regimen modulates differentiation and lactation of bovine mammary gland. Growth Dev Aging. 1989;53(4):159–66.PubMedGoogle Scholar
  88. 88.
    Park CS. Role of compensatory mammary growth in epigenetic control of gene expression. Faseb J. 2005;19(12):1586–91.PubMedGoogle Scholar
  89. 89.
    Choi YJ, Jang K, Yim DS, Baik MG, Myung KH, Kim YS, et al. Effects of compensatory growth on the expression of milk protein gene and biochemical changes of the mammary gland in Holstein cows. J Nutr Biochem. 1998;9(7):380–7.Google Scholar
  90. 90.
    Holliday R, Pugh JE. DNA modification mechanisms and gene activity during development. Science. 1975;187(4173):226–32.PubMedGoogle Scholar
  91. 91.
    Riggs AD. X inactivation, differentiation, and DNA methylation. Cytogenet Cell Genet. 1975;14(1):9–25.PubMedGoogle Scholar
  92. 92.
    Capuco AV, Ellis S. Bovine mammary progenitor cells: current concepts and future directions. J Mammary Gland Biol Neoplasia. 2005;10(1):5–15.PubMedGoogle Scholar
  93. 93.
    Gu B, Sun P, Yuan Y, Moraes RC, Li A, Teng A, et al. Pygo2 expands mammary progenitor cells by facilitating histone H3 K4 methylation. J Cell Biol. 2009;185(5):811–26.PubMedGoogle Scholar
  94. 94.
    Chepko G, Smith GH. Three division-competent, structurally-distinct cell populations contribute to murine mammary epithelial renewal. Tissue Cell. 1997;29(2):239–53.PubMedGoogle Scholar
  95. 95.
    Kordon EC, Smith GH. An entire functional mammary gland may comprise the progeny from a single cell. Development. 1998;125(10):1921–30.PubMedGoogle Scholar
  96. 96.
    Smith GH. Experimental mammary epithelial morphogenesis in an in vivo model: evidence for distinct cellular progenitors of the ductal and lobular phenotype. Breast Cancer Res Treat. 1998;39(1):21–31.Google Scholar
  97. 97.
    Ellis S, Capuco AV. Cell proliferation in bovine mammary epithelium: identification of the primary proliferative cell population. Tissue Cell. 2002;34(3):155–63.PubMedGoogle Scholar
  98. 98.
    Capuco AV, Akers RM. Mammary involution in dairy animals. J Mammary Gland Biol Neoplasia. 1999;4(2):137–44.PubMedGoogle Scholar
  99. 99.
    Yamashita YM, Fuller MT, Jones DL. Signaling in stem cell niches: lessons from the Drosophila germline. J Cell Sci. 2005;118(Pt 4):665–72.PubMedGoogle Scholar
  100. 100.
    Woodward WA, Chen MS, Behbod F, Rosen JM. On mammary stem cells. J Cell Sci. 2005;118(Pt 16):3585–94.PubMedGoogle Scholar
  101. 101.
    Bar-Peled U, Maltz E, Bruckental I, Folman Y, Kali Y, Gacitua H, et al. Relationship between frequent milking or suckling in early lactation and milk production of high producing dairy cows. J Dairy Sci. 1995;78(12):2726–36.PubMedCrossRefGoogle Scholar
  102. 102.
    Hale S, Capuco AV, Erdman RA. Milk yield and mammary growth effects due to increased milking frequency during early lactation. J Dairy Sci. 2003;86(6):2061–71.PubMedCrossRefGoogle Scholar
  103. 103.
    Wall EH, McFadden TB. Optimal timing and duration of unilateral frequent milking during early lactation of dairy cows. J Dairy Sci. 2007;90(11):5042–8.PubMedGoogle Scholar
  104. 104.
    Stelwagen K, Knight CH. Effect of unilateral once or twice daily milking of cows on milk yield and udder characteristics in early and late lactation. J Dairy Res. 1997;64(4):487–94.PubMedGoogle Scholar
  105. 105.
    Stanisiewski EP, Mellenberger RW, Anderson CR, Tucker HA. Effect of photoperiod on milk yield and milk fat in commercial dairy herd. J Dairy Sci. 1985;68(5):1134–40.PubMedCrossRefGoogle Scholar
  106. 106.
    Dahl GE, Petitclerc D. Management of photoperiod in the dairy herd for improved production and health. J Anim Sci. 2003;81 Suppl 3:11–7.PubMedGoogle Scholar
  107. 107.
    Dahl GE. Effects of short day photoperiod on prolactin signaling in dry cows: a common mechanism among tissues and environments? J Anim Sci. 2008;86(13 Suppl):10–4.PubMedGoogle Scholar
  108. 108.
    Miller ARE, Erdman RA, Douglass LW, Dahl GE. Effects of photoperiodic manipulation during the dry period of dairy cows. J Dairy Sci. 2000;83(5):962–7.PubMedCrossRefGoogle Scholar
  109. 109.
    Wall EH, Auchtung-Montgomery TL, Dahl GE, McFadden TB. Short-day photoperiod during the dry period decreases expression of suppressors of cytokine signaling in mammary gland of dairy cows. J Dairy Sci. 2005;88(9):3145–8.PubMedCrossRefGoogle Scholar
  110. 110.
    Barash H, Silanikove N, Weller JI. Effect of season of birth on milk, fat, and protein production of Israeli Holsteins. J Dairy Sci. 1996;79(6):1016–20.PubMedCrossRefGoogle Scholar
  111. 111.
    West JW. Effects of heat-stress on production in dairy cattle. J Dairy Sci. 2003;86(6):2131–44.PubMedCrossRefGoogle Scholar
  112. 112.
    Nienaber JA, Hahn GL. Livestock production system management responses to thermal challenges. Int J Biometeorol. 2007;52(5):149–57.PubMedGoogle Scholar
  113. 113.
    Collier RJ, Doelger SG, Head HH, Thatcher WW, Wilcox CJ. Effects of heat stress during pregnancy on maternal hormone concentrations, calf birth weight and postpartum milk yield of Holstein cows. J Anim Sci. 1982;54(2):309–19.PubMedGoogle Scholar
  114. 114.
    Wolfenson D, Flamenbaum I, Berman A. Dry period heat stress relief effects on prepartum progesterone, calf birth weight, and milk production. J Dairy Sci. 1988;71(3):809–18.PubMedCrossRefGoogle Scholar
  115. 115.
    Adin G, Gelman A, Solomon R, Flamenbaum I, Nikbachat M, Yosef E, et al. Effects of cooling dry cows under heat load conditions on mammary gland enzymatic activity, intake of food and water, and performance during the dry period and after parturition. Livestock Science. 2009;124(1–3):189–95.Google Scholar
  116. 116.
    Rhoads ML, Rhoads RP, Van Baale MJ, Sanders CRJ, SR WWJ, et al. Effects of heat stress and plane of nutrition on lactating Holstein cows: I. Production, metabolism, and aspects of circulating somatotropin. J Dairy Sci. 2009;92(5):1986–97.PubMedGoogle Scholar
  117. 117.
    Collier RJ, Stiening CM, Pollard BC, VanBaale MJ, Baumguard LH, Gentry PC, et al. Use of gene expression microarrays for evaluating environmental stress tolerance at the cellular level in cattle. J Anim Sci. 2006;84(E-suppl):E1–E13.PubMedGoogle Scholar
  118. 118.
    Barker DJP, Gluckman PD, Godfrey KM, Harding JE, Owens JA, Robinson JS. Fetal nutrition and cardiovascular disease in adult life. Lancet. 1993;341(8850):938–41.PubMedGoogle Scholar
  119. 119.
    Barker DJP. Fetal origins of coronary heart disease. BMJ. 1995;311(6998):171–4.PubMedGoogle Scholar
  120. 120.
    Redmer DA, Wallace JM, Reynolds LP. Effect of nutrient intake during pregnancy on fetal and placental growth and vascular development. Domest Anim Endocrinol. 2004;27(3):199–217.PubMedGoogle Scholar
  121. 121.
    McMillen IC, Adams MB, Ross JT, Coulter CL, Simonetta G, Owens JA, et al. Fetal growth restriction: adaptations and consequences. Reproduction. 2001;122(2):195–204.PubMedGoogle Scholar
  122. 122.
    Gartner K. A third component causing random variability beside environment and genotype. A reason for the limited success of a 30 year long effort to standardize laboratory animals? Lab Anim. 1990;24(1):71–7.PubMedGoogle Scholar
  123. 123.
    Peaston AE, Whitelaw E. Epigenetics and phenotypic variation in mammals. Mamm Genome. 2006;17(5):365–74.PubMedGoogle Scholar
  124. 124.
    Wolf JB, Hager R, Cheverud JM. Genomic imprinting effects on complex traits: a phenotype-based perspective. Epigenetics. 2008;3(6):295–9.PubMedCrossRefGoogle Scholar
  125. 125.
    Ruvinsky A. Basics of gametic imprinting. J Anim Sci. 1999;77 Suppl 2:228–37.PubMedGoogle Scholar
  126. 126.
    Moore T, Reik W. Genetic conflict in early development: parental imprinting in normal and abnormal growth. Rev Reprod. 1996;1(2):73–7.PubMedGoogle Scholar
  127. 127.
    Laible G, Brophy B, Knighton D, Wells DN. Compositional analysis of dairy products derived from clones and cloned transgenic cattle. Theriogenology. 2007;67(1):166–77.PubMedGoogle Scholar
  128. 128.
    Pryce JE, Harris BL. Genetics of body condition score in New Zealand dairy cows. J Dairy Sci. 2006;89(11):4424–32.PubMedCrossRefGoogle Scholar
  129. 129.
    Spelman RJ, Miller FM, Hooper JD, Thielen M, Garrick DJ. Experimental design for QTL trial involving New Zealand Friesian and Jersey breeds. Proc 14th AAABG Conference; 2001. p. 393–6.Google Scholar
  130. 130.
    Fox DG, Van Amburgh ME, Tylutki TP. Predicting requirements for growth, maturity, and body reserves in dairy cattle. J Dairy Sci. 1999;82(9):1968–77.PubMedCrossRefGoogle Scholar
  131. 131.
    Erdman RA, Arias JA, Quinn-Walsh E, Fisher P, Stelwagen K, Singh K. Putative in utero epigenetic impacts of dam lactation yield and tissue energy stores on daughter first lactation milk production in dairy cattle. J Dairy Sci. 2009;92(E-Suppl 1):i.Google Scholar
  132. 132.
    Wiggans GR, Misztal I, Van Vleck LD. Implementation of an animal model for genetic evaluation of dairy cattle in the United States. J Dairy Sci. 1988;71 Suppl 2:54–69.Google Scholar
  133. 133.
    Bormann J, Wiggans GR, Druet T, Gengler N. Estimating effects of permanent environment, lactation stage, age, and pregnancy on test-day yield. J Dairy Sci. 2002;85(1):263–83.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Kuljeet Singh
    • 1
  • Richard A. Erdman
    • 2
  • Kara M. Swanson
    • 1
  • Adrian J. Molenaar
    • 1
  • Nauman J. Maqbool
    • 1
  • Thomas T. Wheeler
    • 1
  • Juan A. Arias
    • 3
  • Erin C. Quinn-Walsh
    • 3
  • Kerst Stelwagen
    • 1
  1. 1.AgResearch Ltd.Ruakura Research CentreHamiltonNew Zealand
  2. 2.Department of Animal and Avian SciencesUniversity of MarylandCollege ParkUSA
  3. 3.LICHamiltonNew Zealand

Personalised recommendations