Skip to main content

Marsupial Milk – Identifying Signals for Regulating Mammary Function and Development of the Young

  • Chapter
  • First Online:
Marsupial Genetics and Genomics

Abstract

The role of milk in providing nutrition for the young is well established. However, it is becoming apparent that milk has a more comprehensive role in programming and regulating growth and development of the suckled young, and an autocrine impact on the mammary gland so that it functions appropriately during the lactation cycle. This central role of milk is best studied in animal models, such as marsupials that have evolved a different lactation strategy to eutherians and allow researchers to more easily identify regulatory mechanisms that are not as readily apparent in eutherian species. For example, the tammar wallaby (Macropus eugenii) has evolved with a unique reproductive strategy of a short gestation, birth of an altricial young and a relatively long lactation during which the mother progressively changes the composition of the major, and many of the minor components of milk. Thus, in contrast to eutherians, there is a far greater investment in development of the young during lactation and it is likely that many of the signals that regulate development of eutherian embryos in utero are delivered by the milk. This requires the co-ordinated development and function of the mammary gland. Inappropriate timing of these signalling events in mammals may result in either limited or abnormal development of the young, and potentially a higher incidence of mature onset disease. The tammar is emerging as an attractive model to better understand the role of milk factors in these processes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Andersson B, Porras O, Hanson LA, Lagergard T, Svanborg-Eden C (1986) Inhibition of attachment of Streptococcus pneumoniae and Haemophilus influenzae by human milk and receptor oligosaccharides. J Infect Dis 153:232–237.

    Article  PubMed  CAS  Google Scholar 

  • Backhed F, Ding H, Wang T, et al. (2004) The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci USA 101:15718–15723.

    Article  PubMed  Google Scholar 

  • Backhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI (2005) Host-bacterial mutualism in the human intestine. Science 307:1915–1920.

    Article  PubMed  Google Scholar 

  • Bates JM, Mittge E, Kuhlman J, Baden KN, Cheesman SE, Guillemin K (2006) Distinct signals from the microbiota promote different aspects of zebrafish gut differentiation. Dev Biol 297:374–386.

    Article  PubMed  CAS  Google Scholar 

  • Boehm G, Jelinek J, Stahl B, et al. (2004) Prebiotics in infant formulas. J Clin Gastroenterol 38:S76–S79.

    Article  PubMed  CAS  Google Scholar 

  • Boudreau N, Sympson CJ, Werb Z, Bissell MJ (1995) Suppression of ICE and apoptosis in mammary epithelial cells by extracellular matrix. Science 267:891–893.

    Article  PubMed  CAS  Google Scholar 

  • Brennan AJ, Sharp JA, Lefevre C, et al. (2007) The tammar wallaby and fur seal: models to examine local control of lactation. J Dairy Sci 90:E66–E75.

    Article  PubMed  Google Scholar 

  • Bry L, Falk PG, Midtvedt T, Gordon JI (1996) A model of host-microbial interactions in an open mammalian ecosystem. Science 273:1380–1383.

    Article  PubMed  CAS  Google Scholar 

  • Burdon T, Sankaran L, Wall RJ, Spencer M, Hennighausen L (1991) Expression of a whey acidic protein transgene during mammary development. Evidence for different mechanisms of regulation during pregnancy and lactation. J Biol Chem 266:6909–6914.

    PubMed  CAS  Google Scholar 

  • Clark EA, Brugge JS (1995) Integrins and signal transduction pathways: the road taken. Science 268:233–239.

    Article  PubMed  CAS  Google Scholar 

  • Davis PH (1981) The Post-natal Development of Digestive Proteinases in the Rat (Rattus rattus) and the Tammar Wallaby (Macropus eugenii). University of Sydney, Australia.

    Google Scholar 

  • De Leo AA, Lefevre C, Topcic D, et al. (2006) Characterization of two whey protein genes in the Australian dasyurid marsupial, the stripe-faced dunnart (Sminthopsis macroura). Cytogenet Genome Res 115:62–69.

    Article  PubMed  Google Scholar 

  • Demmer J, Stasiuk SJ, Grigor MR, Simpson KJ, Nicholas KR (2001) Differential expression of the whey acidic protein gene during lactation in the brushtail possum (Trichosurus vulpecula). Biochim Biophys Acta 1522:187–194.

    Article  PubMed  CAS  Google Scholar 

  • Eriksson JG, Forsen T, Tuomilehto J, Osmond C, Barker DJ (2003) Early adiposity rebound in childhood and risk of type 2 diabetes in adult life. Diabetologia 46:190–194.

    PubMed  CAS  Google Scholar 

  • Forsen T, Eriksson J, Tuomilehto J, Reunanen A, Osmond C, Barker D (2000) The fetal and childhood growth of persons who develop type 2 diabetes. Ann Intern Med 133:176–182.

    PubMed  CAS  Google Scholar 

  • Franic TV, Judd LM, Robinson D, et al. (2001) Regulation of gastric epithelial cell development revealed in H(+)/K(+)-ATPase beta-subunit- and gastrin-deficient mice. Am J Physiol Gastrointest Liver Physiol 281:G1502–G1511.

    PubMed  CAS  Google Scholar 

  • Hajjoubi S, Rival-Gervier S, Hayes H, et al. (2006) Ruminants genome no longer contains Whey Acidic Protein gene but only a pseudogene. Gene 370:104–112.

    Article  PubMed  CAS  Google Scholar 

  • Hendry KA, Simpson KJ, Nicholas KR, Wilde CJ (1998) Autocrine inhibition of milk secretion in the lactating tammar wallaby (Macropus eugenii). J Mol Endocrinol 21:169–177.

    Article  PubMed  CAS  Google Scholar 

  • Holmgren J, Svennerholm AM, Lindblad M (1983) Receptor-like glycocompounds in human milk that inhibit classical and El Tor Vibrio cholerae cell adherence (hemagglutination). Infect Immun 39:147–154.

    PubMed  CAS  Google Scholar 

  • Ishikawa K, Satoh Y, Tanaka H, Ono K (1986) Influence of conventionalization on small-intestinal mucosa of germ-free Wistar rats: quantitative light microscopic observations. Acta Anat 127:296–302.

    Article  PubMed  CAS  Google Scholar 

  • Jain RN, Al-Menhali AA, Keeley TM, et al. (2008) Hip1r is expressed in gastric parietal cells and is required for tubulovesicle formation and cell survival in mice. J Clin Invest 118:2459–2470.

    Article  PubMed  CAS  Google Scholar 

  • Janssens PA, Ternouth JH (1987) The transition from milk to forage diets. In: Hacker JB, Ternouth JH (eds) The Nutrition of Herbivores. Academic Press, London and New York.

    Google Scholar 

  • Karam SM (1995) New insights into the stem cells and the precursors of the gastric epithelium. Nutrition 11:607–613.

    PubMed  CAS  Google Scholar 

  • Karam SM (1999) Lineage commitment and maturation of epithelial cells in the gut. Front Biosci 4:D286–D298.

    Article  PubMed  CAS  Google Scholar 

  • Kelly D, King T, Aminov R (2007) Importance of microbial colonization of the gut in early life to the development of immunity. Mutat Res 622:58–69.

    Article  PubMed  CAS  Google Scholar 

  • Kunz C, Rudloff S (2008) Potential anti-inflammatory and anti-infectious effects of human milk oligosaccharides. Adv Exp Med Biol 606:455–465.

    Article  PubMed  CAS  Google Scholar 

  • Kunz C, Rudloff S, Baier W, Klein N, Strobel S (2000) Oligosaccharides in human milk: structural, functional, and metabolic aspects. Annu Rev Nutr 20:699–722.

    Article  PubMed  CAS  Google Scholar 

  • Kwek J, De Iongh R, Nicholas K, Familari M (2009a) Molecular insights into evolution of the vertebrate gut: focus on stomach and parietal cells in the marsupial, Macropus eugenii. J Exp Zool B Mol Dev Evol 312:613–624.

    Article  PubMed  Google Scholar 

  • Kwek JH, Iongh RD, Digby MR, Renfree MB, Nicholas KR, Familari M (2009b) Cross-fostering of the tammar wallaby (Macropus eugenii) pouch young accelerates fore-stomach maturation. Mech Dev 126:449–463.

    Article  PubMed  CAS  Google Scholar 

  • Lefèvre CM, Digby MR, Whitley JC, Strahm Y, Nicholas KR (2007) Lactation transcriptomics in the Australian marsupial, Macropus eugenii: transcript sequencing and quantification. BMC Genomics 8:417–425.

    Article  PubMed  Google Scholar 

  • Li M, Liu X, Robinson G, et al. (1997) Mammary-derived signals activate programmed cell death during the first stage of mammary gland involution. Proc Natl Acad Sci USA 94:3425–3430.

    Article  PubMed  CAS  Google Scholar 

  • Li Q, Karam SM, Gordon JI (1995) Simian virus 40 T antigen-induced amplification of pre-parietal cells in transgenic mice. Effects on other gastric epithelial cell lineages and evidence for a p53-independent apoptotic mechanism that operates in a committed progenitor. J Biol Chem 270:15777–15788.

    Article  PubMed  CAS  Google Scholar 

  • Li Q, Karam SM, Gordon JI (1996) Diphtheria toxin-mediated ablation of parietal cells in the stomach of transgenic mice. J Biol Chem 271:3671–3676.

    Article  PubMed  CAS  Google Scholar 

  • Marti A, Feng Z, Altermatt HJ, Jaggi R (1997) Milk accumulation triggers apoptosis of mammary epithelial cells. Eur J Cell Biol 73:158–165.

    PubMed  CAS  Google Scholar 

  • Marti A, Lazar H, Ritter P, Jaggi R (1999) Transcription factor activities and gene expression during mouse mammary gland involution. J Mammary Gland Biol 4:145–152.

    Article  CAS  Google Scholar 

  • Newburg DS (1996) Oligosaccharides and glycoconjugates in human milk: their role in host defense. J Mammary Gland Biol 1:271–283.

    Article  CAS  Google Scholar 

  • Newburg DS (1997) Do the binding properties of oligosaccharides in milk protect human infants from gastrointestinal bacteria? J Nutr 127:980S–984S.

    PubMed  CAS  Google Scholar 

  • Nicholas K, Simpson K, Wilson M, Trott J, Shaw D (1997a) The tammar wallaby: a model to study putative autocrine-induced changes in milk composition. J Mammary Gland Biol 2:299–310.

    Article  CAS  Google Scholar 

  • Nicholas KR (1988a) Asynchronous dual lactation in a marsupial, the tammar wallaby (Macropus eugenii). Biochem Biophys Res Commun 154:529–536.

    Article  PubMed  CAS  Google Scholar 

  • Nicholas KR (1988b) Control of milk protein synthesis in the tammar wallaby:a model system to study prolactin-dependent development. In: Tyndale-Biscoe CH, Janssens PA (eds) The Developing Marsupial: Models for Biomedical Research. Springer, Heidelberg.

    Google Scholar 

  • Nicholas KR, Tyndale-Biscoe CH (1985) Prolactin-dependent accumulation of alpha-lactalbumin in mammary gland explants from the pregnant tammar wallaby (Macropus eugenii). J Endocrinol 106:337–342.

    Article  PubMed  CAS  Google Scholar 

  • Nicholas KR, Wilde C, Bird K, Hendry K, Tregenza K, Warner B (1995) Asynchronous concurrent secretion of milk proteins in the tammar wallaby (Macropus eugenii). In: Wilde C, Knight C, Peaker M (eds) Intercellular Signalling in the Mammary Gland. Plenum Press, London.

    Google Scholar 

  • Nicholas KR, Simpson K, Wilson M, Trott J, Shaw D (1997b) The tammar wallaby: a model to study putative autocrine-induced changes in milk composition. J Mammary Gland Biol 2: 299–310.

    Article  CAS  Google Scholar 

  • Nicholas KR, Fisher JA, Muths E, et al. (2001) Secretion of whey acidic protein and cystatin is down regulated at mid-lactation in the red kangaroo (Macropus rufus). Comp Biochem Physiol A Mol Integr Physiol 129:851–858.

    Article  PubMed  CAS  Google Scholar 

  • Nukumi N, Ikeda K, Osawa M, Iwamori T, Naito K, Tojo H (2004) Regulatory function of whey acidic protein in the proliferation of mouse mammary epithelial cells in vivo and in vitro. Dev Biol 274:31–44.

    Article  PubMed  CAS  Google Scholar 

  • Phillips DIW (2001) Non-insulin-dependent diabetes and obesity. In: Barker DJ (ed) Fetal Origins of Cardiovascular and Lung Disease. Marcel Dekker, New York.

    Google Scholar 

  • Quarrie LH, Addey CVP, Wilde CJ (1996) Programmed cell death during mammary tissue involution induced by weaning, litter removal and milk stasis. J Cell Physiol 168:559–569.

    Article  PubMed  CAS  Google Scholar 

  • Ranganathan S, Simpson KJ, Shaw DC, Nicholas KR (1999) The whey acidic protein family: a new signature motif and three-dimensional structure by comparative modeling. J Mol Graph Model 17:106–113, 134–136.

    Article  PubMed  CAS  Google Scholar 

  • Sdassi N, Silveri L, Laubier J, et al. (2009) Identification and characterization of new miRNAs cloned from normal mouse mammary gland. BMC Genomics 10:149.

    Article  PubMed  Google Scholar 

  • Silveri L, Tilly G, Vilotte JL, Le Provost F (2006) MicroRNA involvement in mammary gland development and breast cancer. Reprod Nutr Dev 5:549.

    Article  Google Scholar 

  • Sharp JA, Lefevre C, Nicholas KR (2007) Molecular evolution of monotreme and marsupial whey acidic protein genes. Evol Dev 9:378–392.

    Article  PubMed  CAS  Google Scholar 

  • Sharp JA, Lefevre C, Nicholas KR (2008) Lack of functional alpha-lactalbumin prevents involution in Cape fur seals and identifies the protein is an apoptotic milk factor in mammary gland involution. BMC Biol 6:48.

    Article  PubMed  Google Scholar 

  • Sharp JA, Digby M, Lefevre C, et al. (2009) The comparative genomics of tammar wallaby and fur seal lactation; models to examine function of milk proteins. In: Thompson A, Boland M, Singh H (eds) Milk Proteins: From Expression to Food. Academic Press, New York.

    Google Scholar 

  • Simpson KJ, Ranganathan S, Fisher JA, Janssens PA, Shaw DC, Nicholas KR (2000) The gene for a novel member of the whey acidic protein family encodes three four-disulfide core domains and is asynchronously expressed during lactation. J Biol Chem 275:23074–23081.

    Article  PubMed  CAS  Google Scholar 

  • Simpson KJ, Nicholas KR (2002) The comparative biology of whey proteins. J Mammary Gland Biol 7:313–326.

    Article  Google Scholar 

  • Tanaka T, Haneda S, Imakawa K, Sakai S, Nagaoka K (2009) A microRNA, miR-101a, controls mammary gland development by regulating cyclooxygenase-2 expression. Differentiation 77:181–187.

    Article  PubMed  CAS  Google Scholar 

  • Topcic D, Auguste A, De Leo AA, Lefevre C, Digby MR, Nicholas KR (2009) Characterization of the tammar wallaby (Macropus eugenii) whey acidic protein gene: new insights into the function of the protein. Evol Dev 11:363–375.

    Article  PubMed  CAS  Google Scholar 

  • Triplett AA, Sakamoto K, Matulka LA, Shen L, Smith GH, Wagner KU (2005) Expression of the whey acidic protein (Wap) is necessary for adequate nourishment of the offspring but not functional differentiation of mammary epithelial cells. Genesis 43:1–11.

    Article  PubMed  CAS  Google Scholar 

  • Trott JF, Wilson MJ, Hovey RC, Shaw DC, Nicholas KR (2002) Expression of novel lipocalin-like milk protein gene is developmentally-regulated during lactation in the tammar wallaby, Macropus eugenii. Gene 283:287–297.

    Article  PubMed  CAS  Google Scholar 

  • Trott JF, Simpson KJ, Moyle RL, et al. (2003) Maternal regulation of milk composition, milk production, and pouch young development during lactation in the tammar wallaby (Macropus eugenii). Biol Reprod 68:929–936.

    Article  PubMed  CAS  Google Scholar 

  • Tyndale-Biscoe CH, Janssens PA (1988) The Developing Marsupial: Models for Biomedical Research. Springer, Heidelberg.

    Book  Google Scholar 

  • Uribe A, Alam M, Johansson O, Midtvedt T, Theodorsson E (1994) Microflora modulates endocrine cells in the gastrointestinal mucosa of the rat. Gastroenterology 107:1259–1269.

    PubMed  CAS  Google Scholar 

  • Waite R, Giraud A, Old J, et al. (2005) Cross-fostering in Macropus eugenii leads to increased weight but not accelerated gastrointestinal maturation. J Exp Zool Part A 303:331–344.

    Google Scholar 

  • Wang C, Li Q (2007) Identification of differentially expressed microRNAs during the development of Chinese murine mammary gland. J Genet Genomics 34:966–973.

    Article  PubMed  CAS  Google Scholar 

  • Ward RE, Ninonuevo M, Mills DA, Lebrilla CB, German JB (2006) In vitro fermentation of breast milk oligosaccharides by Bifidobacterium infantis and Lactobacillus gasseri. Appl Environ Microb 72:4497–4499.

    Article  CAS  Google Scholar 

  • Wilde CJ, Addey CVP, Boddy-Finch L, Peaker M (1995) Autocrine control of milk secretion: from concept to application. In: Intercellular Signalling in the Mammary Gland. Plenum Press, New York.

    Chapter  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kevin R. Nicholas .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Sharp, J.A. et al. (2010). Marsupial Milk – Identifying Signals for Regulating Mammary Function and Development of the Young. In: Deakin, J., Waters, P., Marshall Graves, J. (eds) Marsupial Genetics and Genomics. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9023-2_15

Download citation

Publish with us

Policies and ethics