Source: UNIVERSITY OF VERMONT submitted to
ENHANCING BOVINE MAMMARY DEVELOPMENT TO IMPROVE MILK PRODUCTION EFFICIENCY
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
TERMINATED
Funding Source
Reporting Frequency
Annual
Accession No.
0186119
Grant No.
(N/A)
Project No.
VT-AS-00717
Proposal No.
(N/A)
Multistate No.
(N/A)
Program Code
(N/A)
Project Start Date
Oct 1, 2000
Project End Date
Sep 30, 2004
Grant Year
(N/A)
Project Director
McFadden, T. B.
Recipient Organization
UNIVERSITY OF VERMONT
(N/A)
BURLINGTON,VT 05405
Performing Department
ANIMAL SCIENCE
Non Technical Summary
Milk production of dairy cows is highly dependent on optimal udder development and mammary function. The purpose of this project is to identify key genes that regulate mammary function and determine relationships between gene expression profiles and mammary development and function.
Animal Health Component
(N/A)
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3043499102010%
3043499104010%
3053499102070%
3053499104010%
Goals / Objectives
1) To Determine gene expression profiles in mammary parenchymal and stromal tissues of dairy heifers after treatment with estrogen, growth hormone, or the combination of the two; and 2) To determine gene expression profiles in mammary parenchyma of lactating cows, at various stages of development and lactation.
Project Methods
Changes in gene expression in mammary tissues of heifers and lactating cows will be determined by low density gene arrays and confirmed by Northern analysis. Key genes and pathways involved in mammary cell proliferation, and in mammary function, will be identified and relationships with other measures of mammary development and function will be determined.

Progress 10/01/00 to 09/30/04

Outputs
We have identified several genes that are regulated during mammary development by using low-density cDNA arrays as an initial screen and quantitative real-time RT-PCR to determine gene expression profiles. Several of these genes have not been previously studied in bovine mammary gland. These include several members of the SOCS family, as well as the putative vitamin receptors, megalin, cubilin, folic acid receptor-alpha, and low-density lipoprotein receptor (LDL-R). We have conducted studies on the effects of the transition from gestation to lactation, hormonal induction of lactation, photoperiod and frequent milking. In each of these we have quantified effects of treatments or physiological stage on indices of mammary gland development and function. Experiments on photoperiod and frequent milking led to the identification of prolactin signaling as a possible common regulator of mammary function and milk yield. These treatments were associated with significant changes in mammary expression of SOCS genes, as well as that of prolactin receptor. Our data also demonstrated that exposure of cows to short-day photoperiod during the dry period resulted in significant effects on proliferation and apoptosis of mammary cells, particularly at about 20 days prior to parturition. These findings indicate that the enhancement of milk yield shown to follow this treatment is due, at least partly, to changes in mammary development during the dry period. This study also demonstrated that expression of IGF-2 mRNA in mammary gland increased significantly during gestation and was elevated in cows exposed to short-days, suggesting a potential role in regulation of mammary growth. Studies on the regulation of colostrum formation revealed that mammary expression of megalin and LDL-R mRNA is markedly upregulated at the time of colostrogenesis, coincident with changes in indicators of colostrum formation in blood and mammary secretions. These receptors may function in transport of fat-soluble vitamins into colostrum and thereby influence calf health. Research on pubertal heifers hormonally induced into lactation demonstrated that exposure to short-day photoperiod before and during the hormonal treatment resulted in significantly increased milk yield relative to heifers on long-days, thereby confirming the stimulatory effect of short-days previously reported in dry cows.

Impacts
By identifying several genes involved in regulation of mammary development and function we have identified new potential targets for development of treatments or optimized management strategies that could enhance mammary development, milk production, colostral quality and calf health.

Publications

  • Musters, S., K. Coughlan, T. McFadden, R. Maple, T. Mulvey, and K. Plaut. 2004. Exogenous TGF-b1 promotes stromal development in the heifer mammary gland. J. Dairy Sci. 87:896-904.
  • Singh, K., D.G. Hartley, T.B. McFadden and D.D. Mackenzie. 2004. Dietary fat regulates mammary stearoyl coA desaturase expression and activity in lactating mice. J. Dairy Res. 71:1-6.
  • Wall, E.H., T.L. Auchtung, G.E. Dahl and T.B. McFadden. 2004. Exposure to short day photoperiod enhances mammary growth during the dry period of dairy cows. J. Dairy Sci. 87(Suppl. 1):94.
  • Wall, E.H., H.M. Crawford, G.E. Dahl and T.B. McFadden. 2004. Expression of prolactin responsive genes following experimental manipulation of the prolactin axis during early lactation in dairy cows. J. Dairy Sci. 87(Suppl. 1):423.
  • Wall, E.H., T.L. Auchtung, G.E. Dahl and T.B. McFadden. 2004. Exposure to long day photoperiod during the dry period increases mammary gland expression of suppressors of cytokine signaling in dairy cows. J. Dairy Sci. 87(Suppl. 1):423-424.
  • Martinez, D.G., G.E. Dahl and T.B. McFadden. 2004. Mechanisms of transport of vitamins into colostrum: A potential role of megalin and low-density lipoprotein receptor. J. Dairy Sci. 87(Suppl. 1):128.
  • Martinez, D.G., R. Thomason and T.B. McFadden. 2004. Changes in expression of vitamin receptors in bovine mammary gland during hormone induced colostrogenesis. J. Dairy Sci. 87(Suppl. 1):133-134.
  • Martinez, D.G., R. Thomason and T.B. McFadden. 2004. Comparison of gene expression changes in the two subunits of bovine IgG1 receptor during colostrogenesis. J. Dairy Sci. 87(Suppl. 1):133.
  • Zhao, F., P. Miller, E.H. Wall, Y. Zheng, B. Dong and T.B. McFadden. 2004. Cloning and expression of bovine glucose transporter GLUT8. J. Dairy Sci. 87(Suppl. 1):133.
  • Reid, E.D., T.L. Auchtung, D.E. Morin, T.B. McFadden and G.E. Dahl. 2004. Effects of 21-day short day photoperiod (SDPP) during the dry period on prolactin (PRL) concentrations, lymphocyte PRL receptor (PRL-R) mRNA, and general health of dairy cows. J. Dairy Sci. 87(Suppl. 1):423.
  • Reid, E.D., R.L. Wallace, T.B. McFadden and G.E. Dahl. 2004. The effects of a 21-day short day photoperiod treatment during the dry period on dry matter intake and subsequent milk production in cows. J. Dairy Sci. 87(Suppl. 1):424.
  • Crawford, H.M., T.L. Auchtung, E.H. Wall, T.B. McFadden and G.E. Dahl. 2004. Evidence that prolactin (PRL) mediates effects of milking frequency in early lactation. J. Dairy Sci. 87(Suppl. 1):424.


Progress 01/01/03 to 12/31/03

Outputs
We are studying the effects of gestation, hormonal induction of lactation, and photoperiod treatment to identify genes that are involved in regulation of mammary development and function. We have identified several genes in the prolactin signaling pathway that are regulated by photoperiod and change expression during pregnancy or hormone treatment. We have also identified several genes that appear to be involved in transport of colostral components from maternal blood into mammary secretions. By studying the expression of these genes we aim to develop or optimize methods for enhancing milk yield and improving milk composition and calf health.

Impacts
By identifying key genes that control mammary development and function and understanding how they are regulated we can develop new treatments and/or optimize management strategies to enhance milk production and milk quality.

Publications

  • Wall, E., R. Thomason, D. Maynard, E. Brunst and T.B. McFadden. 2003. Abnormal udder conformation in pubertal heifers induced into lactation. J. Dairy Sci. 86(Suppl. 1):11.
  • Thomason, R., D. Martinez, G.E. Dahl and T.B. McFadden. 2003. Photoperiod manipulation affects milk yield and mammary growth in pubertal heifers induced to lactate. J. Dairy Sci. 86(Suppl. 1):11.
  • Rius, A.G., T.L. Auchtung, P.E. Kendall, T.B. McFadden and G.E. Dahl. 2003. Evidence for shifts in prolactin sensitivity in cows exposed to long or short day photoperiod during the dry period. J. Dairy Sci. 86(Suppl. 1):244.
  • Mabjeesh, S.J., A. Shamay, G.E. Dahl and T.B. McFadden. 2003. Exposure to short days during the dry period increases milk production in subsequent lactation in dairy goats. J. Dairy Sci. 86(Suppl. 1):283.
  • Musters, S., T.B. McFadden, T. Mulvey, K. Coughlan, R. Maple and K. Plaut. 2003. Implantation of a pellet containing TGF-b increases BrdU-labeling in mammary stromal cells of prepubertal heifers. J. Dairy Sci. 86(Suppl. 1):31.
  • Auchtung, T.L., P.E. Kendall, J.L. Salak-Johnson, T.B. McFadden and G.E. Dahl. 2003. Photoperiod and bromocriptine treatment effects on expression of prolactin receptor mRNA in bovine liver, mammary gland and peripheral blood lymphocytes. J. Endocrinol. 179:347-356.
  • McFadden, T.B. 2003. Effects of bioactive components of colostrum and milk on neonatal health, growth and intestinal development. J. Dairy Sci. 86(Suppl. 1):135.


Progress 02/15/02 to 02/14/03

Outputs
An experiment on hormonal induction of lactation in dairy heifers was completed and mammary biopsy samples were collected. Hormonal induction evoked a significant increase in proliferation of mammary cells. Heifers exposed to short day photoperiod during induction produced significantly more milk than those exposed to long days. In a second experiment, serial mammary biopsy samples were obtained from dry cows at several stages of gestation. Several cell culture experiments were completed and others are ongoing. Samples obtained from these trials are being analyzed, using low density cDNA arrays and real-time PCR, to determine changes in gene expression and relate them to indicators of mammary development and function. Based on preliminary results, studies are focusing on at least six genes that were differentially expressed. Five abstracts have been submitted.

Impacts
This project is expected to identify some of the key genes that regulate mammary development in dairy cows and how they might be manipulated to enhance udder growth. If successful, this would be expected to increase the efficiency of milk production.

Publications

  • Neville, M.C., T.B. McFadden and I.A. Forsyth. 2002. Hormonal regulation of mammary differentiation and milk secretion. J. Mammary Gland Biol. Neoplasia 7:49-66.
  • McFadden, T.B. 2002. Proliferation-associated gene expression in bovine mammary gland. J. Dairy Sci. 85(Suppl. 1):3.
  • Auchtung, T.L., B.C. Pollard, P.E. Kendall, T.B. McFadden and G.E. Dahl. 2002. Prolactin receptor expression responds to photoperiod similarly in multiple tissues in dairy cattle. J. Anim. Sci. 80(Suppl. 1):9.


Progress 01/01/01 to 12/31/01

Outputs
Progress on objective 1 is nearing completion: Low density gene arrays have been prepared and final characterization of assay performance is underway. Experiments on objectives 3 and 4 have been initiated and sample collection and analyses are underway. Work on objective 2 will begin in FY 2003.

Impacts
This project is expected to identify some of the important genes that control mammary development in dairy heifers and how they might be manipulated to enhance udder growth. If successful, this would be expected to increase the efficiency of milk production.

Publications

  • Berry, S.D., McFadden, T.B., Pearson, R.E. and Akers, R.M. 2001. A local increase in the mammary IGF-1:IGFBP-3 ratio mediates the mammogenic effects of estrogen and growth hormone. Dom. Anim. Endocrinol. 21:39-53.
  • Barrington, G.M., McFadden, T.B., Huyler, M.T. and Besser, T.E. 2001. Regulation of colostrogenesis in cattle. Livest. Prod. Sci. 70:95-104.
  • Hovey, R.C., Davey, H.W., Vonderhaar, B.K., Mackenzie, D.D.S. and McFadden, T.B. 2001. Paracrine action of keratinocyte growth factor (KGF) during ruminant mammogenesis. Mol. Cell. Endocrinol. 181:47-56.
  • Berry, S.D., McFadden, T.B., Pearson, R.E. and Akers, R.M. 2001. Mammogenic effects of estrogen and growth hormone are mediated by local changes in mammary IGF-1 and IGFBP-3. J. Dairy Sci. 84(Suppl. 1):102.