Published December 5, 2014
Nutrition in mammary gland health and lactation: Advances over eight Biology of Lactation in Farm Animals meetings1 A. Baldi,2 F. Cheli, L. Pinotti, and C. Pecorini Department of Veterinary Science and Technology for Food Safety, University of Milan, Italy
neonates and adults. In the past, attempts to probe the relationship among nutrition, animal health, and animal products were limited to administering single dietary components and investigating their biochemical and metabolic effects. Today, we have genomics, proteomics, and related technologies that allow us to pursue more holistic investigational strategies. These new technologies are providing new insights into interactions among nutrition, lactation, and product quality. The aim of this paper is to review advances in nutritional support of mammary gland function and health as presented in 14 yr of Biology of Lactation in Farm Animals (BOLFA) meetings.
ABSTRACT: Over the years, numerous studies have investigated the mechanisms controlling nutrient availability and metabolism in the mammary gland and how dietary interventions can influence these processes. The development of in vivo and in vitro systems made it possible to explore the trafficking and metabolic fate of nutrients and how these are influenced by hormones. To improve the quality and safety of milk products, attention has focused on improving animal health in general and mammary gland health in particular and also on enhancing the milk content of natural bioactive milk components that promote the health of human
Key words: nutrition, mammary gland, farm animal, lactation ©2008 American Society of Animal Science. All rights reserved.
INTRODUCTION
J. Anim. Sci. 2008. 86(Suppl. 1):3–9 doi:10.2527/jas.2007-0286
between nutrition and development, function, and health of the mammary gland. The topics explored in the 8 BOLFA meetings include precursors of and metabolic support for lactation; uptake and metabolism of nutrients by the mammary gland; manipulation of milk components; and interactions among genes, nutrition, and the endocrine system. The role of milk as means of delivering nutrients and bioactive compounds in promoting human and neonate health also was addressed. Thus, these meetings have provided a series of snapshots documenting the development of research in nutrition and lactation over the past 2 decades, with particular attention on the comprehension of basic mechanisms underpinning mammary gland function. This paper reviews aspects of nutrition and lactation, as examined at the previous BOLFA meetings, focusing on dairy cows; however, many of the concepts discussed are applicable to other farm animals.
Over the years, numerous studies have been presented in the Biology of Lactation in Farm Animals (BOLFA) workshops on the mechanisms controlling nutrient availability and metabolism in the mammary gland, and how dietary interventions can influence these processes. The first BOLFA workshop took place in Madrid in 1992, and subsequent workshops have been held every 2 yr since then (Figure 1). The event serves as a forum for presenting the results of basic and applied research on the mammary gland so as to increase understanding of lactation in farm animals and has been successful in encouraging the free exchange of scientific ideas on a broad range of topics centering on the biology of the mammary gland. Scientific progress has been rapid since 1992, and BOLFA meetings have reflected that progress. A key issue throughout all the meetings has been the relationship
NUTRIENT SUPPLY AND THE METABOLIC SUPPORT OF LACTATION
1
Presented at the Eighth International Workshop on the Biology of Lactation in Farm Animals held in Pirassununga, Brazil, August 21–23, 2006. 2 Corresponding author:
[email protected] Received May 21, 2007. Accepted July 17, 2007.
Initially, the studies presented on the topic of supply of metabolic precursors to support lactation described mainly the uptake, utilization efficiency, and metabolism of amino acids by the mammary gland, and quanti3
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Figure 1. Locations and dates of the Biology of Lactation in Farm Animals (BOLFA) workshops. fied input-output relationships between nutrient availability and protein secretion. One aim of those studies was to increase milk protein content by using dietary manipulation to increase the amino acid supply to the mammary gland (Murphy and O’Mara, 1993). In fact, feeding greater amounts of concentrates increases milk protein concentration and milk yield. Infusion of casein or essential amino acids postruminally also increases milk protein concentration, but responses to feeding rumen-protected lysine and methionine have been variable and dependent on the stage of lactation, as presented by Rulquin (Rulquin et al., 1993) at the second BOLFA workshop in Minneapolis. Metcalf and coworkers (1994) found that short-term udder infusion of amino acids in lactating dairy cows resulted in greater milk removal (i.e., 55 to 73%) from the infused mammary gland than from the noninfused gland. Those results indicated that mammary gland uptake of amino acids was influenced by blood levels of amino acids, although their subsequent fates were not entirely clear. Some information on the fate of amino acids in the mammary gland was provided by studies in goats that indicated that net uptake of amino acids available for protein synthesis (and therefore, not oxidized) by the mammary gland, were, in decreasing order, methionine, phenylalanine, threonine, histidine, and lysine (Bequette et al., 1994). This order of amino acid availability has been suggested as an indicator of amino acid priority for milk protein synthesis.
Although studies on the amino acids, which are limiting for milk production, have focused mainly on essential amino acids, the potentially limiting influence of nonessential amino acids also was investigated (Meijer and van der Koelen, 1994). Glutamine, in particular, has been studied both for its contribution to milk proteins, and for its multiple roles in the body. Glutamine and glutamate are the major amino acids of milk proteins, constituting approximately 20% of casein amino acids. Two other features of ruminant glutamine metabolism are important in this context: 1) the low capacity of ruminants to synthesize glutamine compared with monogastric animals and 2) the response of plasma and tissue glutamine pools to conditions of metabolic stress, including high milk production, which resemble those of most essential amino acids (Meijer et al., 1993). In the postpartum dairy cow, the rapid increase in milk yield, simultaneous increase in gut tissue growth, and the need to synthesize glucose may lead to glutamine deficiency, particularly in the early postcalving period, and thereby constitute a limitation on milk yield (Meijer et al., 1995). At the 1998 BOLFA workshop in Denver, Colorado, Petitclerc et al. (2000) examined the genetic relationship among milk yield, feed intake, and feed efficiency; discussed how rumen function (i.e., carbohydrate digestion, vitamin B requirements, and fatty acid biohydrogenation) could be manipulated to influence milk yield and composition; and discussed the importance of glu-
Nutrition in mammary gland health
cose, which is essential for milk synthesis in both ruminants and nonruminants. In particular, postruminal glucose supply, which enhances glucose absorption, can balance glucose utilization by portally drained viscera, sparing endogenous glucose and glucose precursors and, therefore, increasing total glucose availability to the rest of the body, including the lactating mammary gland. At the 2000 BOLFA meeting in The Hague, Hanigan et al. (2001) examined the various models proposed to predict milk protein yield. Important components of these models are mammary gland amino acid metabolism that is regulated by amino acid supply and other factors, such as energy metabolism, regulation of amino acids uptake, and mammary blood flow. The secretory side of the model also must be represented and requires terms for amino acid oxidation, as well as for protein synthesis. Hanigan et al. (2001) concluded that a multisubstrate Michaelis-Menten equation form is more consistent with experimental observations and appears to yield better predictions than single-limiting models. From these studies, it was evident that although the amino acid supply influences milk protein concentration and yield (kg of protein/d), the transfer efficiency of dietary protein to milk is low. Probably this low efficiency of dietary protein to milk is a major factor accounting for the inability of diet to markedly alter milk protein content, as also reviewed recently by Jenkins and McGuire (2006). However, studies with cows under hyperinsulinemic-euglycemic clamp showed that mammary amino acid extraction can be adjusted to enhance milk protein secretion (McGuire et al., 1994). This finding indicates that substrate uptake from the blood can be responsive to changes in arterial amino acid concentrations, mammary blood flow, and metabolic activity. Milk fat content is much more susceptible to dietary manipulation in relation to the origin of milk fatty acids in dairy ruminants. Approximately 50% of short- and medium-chain fatty acids (C4:0 to C16:0) in milk arise from de novo synthesis in the mammary gland from acetate and β-hydroxybutyrate of ruminal origin, whereas one-half the palmitic acid and most of the longchain fatty acids of milk arise from uptake into the mammary gland of lipids from blood. In cows, diets rich in concentrates, vegetable oils, or fish oil, and those diets characterized by small particle size can induce major milk fat depression. By contrast, an increase in milk fat content occurs when encapsulated lipids are fed (Chilliard et al., 2001). However, these changes in milk fatty acid content are generally accompanied by a major modification in fatty acid profile. Chilliard and coworkers (2001), in the fifth BOLFA workshop, summarized the effects of dietary factors on milk fat secretion and composition, concentrating on the ability of different diet formulations to decrease milk fat content or enhance unsaturated fatty acid concentration to obtain healthier milk for human consumption (see subsequent discussion).
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Other topics covered at BOLFA meetings were the roles of metabolic hormones in regulating milk synthesis, including the effect of insulin on milk protein and fat yields, and the modulation exerted by somatotropin and insulin-like growth factors (Flint et al., 2001; Knight, 2001). Insulin has acute effects on adipose lipogenesis (stimulatory) and lipolysis (inhibitory), but the ruminant mammary gland is unresponsive to changes in circulating insulin, which has no apparent effect on glucose uptake or utilization by the mammary gland. By inhibiting adipose lipolysis, insulin seems to limit the supply of milk fat precursors available to the udder, thus supporting the glucogenic-insulin theory as a cause of milk fat depression (Bauman and Griinari, 2001). With respect to increases in milk proteins, Petitclerc et al. (2000) suggested that insulin can act directly on either mammary epithelial cell proliferation or amino acids transport systems in the mammary cells or indirectly via increases in IGF-I that involve ST. Somatotropin exerts a systemic effect on all types of nutrients repartitioning them toward the udder, and also on the local production of IGF in the mammary gland (Capuco et al., 2003). The effects of ST administration depend on nutritional status, and when nutritional status is excellent, it produces a substantial increase in milk yield. Specific changes induced by ST via IGF include greater milk synthesis by secretory cells and enhanced survival of secretory cells. Insulinlike growth factor-I was proposed to be a cell survival factor necessary to prevent apoptotic death, as well as being involved in remodeling events of mammary gland involution (Knight and Wilde, 1993). It may therefore be possible to use ST to extend lactation, as was discussed in Lillehammer (Knight, 1997; van Amburgh et al., 1997) and by Capuco et al. (2003) in Quebec City. The influence of nutrient supply on lactation also has been investigated in other species, including sows (Hartmann et al., 1997; Farmer and Sørensen, 2001; Pere`z Laspiur and Trottier, 2001), ewes (Baldi et al., 1997), goats (Knight, 1997; Wilde et al., 1997), and mares (Dell’Orto et al., 1994a,b; Deichsel and Aurich, 2005). Metabolic mechanisms relating nutrient intake and lactation performance in the sow were discussed in several BOLFA workshops. In particular, lipid metabolism in adipose tissue and dietary amino acids, particularly lysine, were shown to be key factors influencing milk production in sows (Pettigrew et al., 1993). In this field, further progress in amino acid nutrition to maximize genetic potential for litter weight gain and milk production of sows was provided by Trottier and Guan (2000). In discussing amino acid requirements of the sow, those authors indicated that it is essential not only to identify which amino acids pools are significant for the mammary system, but also to understand nutrient interactions in order to obtain an optimal response. Farmer and Sørensen (2001) highlighted the importance of optimal nutrition in prepubertal gilts as a factor influencing mammary development and subsequent milk production. Those authors also found that high
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energy intake by sows during gestation may have detrimental effects on mammary development and milk production, whereas dietary protein had limited effects on mammary development but could increase subsequent milk production.
NUTRIENT UPTAKE, TRAFFICKING, AND FUNCTION AT THE CELLULAR LEVEL Most of the results obtained in the 1990s in the area of nutrients uptake were derived from in vivo experiments, particularly lactation trials and arteriovenous difference studies. Although useful information was obtained from arteriovenous difference studies, they provided little insight into how intracellular nutrients metabolism and trafficking are regulated in the mammary gland and cannot easily address some aspects such as mammary cell changes during puberty, pregnancy, and lactation or the influence of hormones on mammary development, mammary involution, or nutrient utilization for milk synthesis (Wilde et al., 1997; Purup et al., 2000). Studies on secretory pathways within mammary cells led to important advances in our understanding of the biology of lactation. In the Hague meeting in 2000, Boisgard et al. (2001) noted that protein milk composition results from two main processes; the expression of milk protein encoding genes in the mammary epithelial cells and the transfer of plasma-borne proteins. An anterograde secretory pathway is responsible for the secretion of newly synthesized proteins in milk, such as caseins and whey proteins. Following this pathway, the proteins initially appear on the endoplasmic reticulum, transiently associate with elements of the Golgi complex, and then concentrate in post-Golgi secretory vesicles before being exported into milk. Beside this main anterograde transport, a transcytotic pathway is responsible for the transfer of bioactive components (e.g., hormones, growth factors, and immunoglobulins) from the blood or from stroma cells into milk (Boisgard et al., 2001). In vitro studies using mammary explants, immortalized cell lines, barrier systems, and alveolilike structures were vital for elucidating these aspects of uptake and trafficking. In vitro experimental models of milk secretion also were appraised for investigating nutrient roles beyond that of supporting milk component synthesis. In particular, they were used to monitor the effects of interventions to alter the quality or composition of nutrient output during lactation (Clegg et al., 2001). An increasingly wide variety of biotechnological tools are now becoming available to elucidate the complex physiology of the mammary gland. Microarrays for transcriptional profiling and proteomic analyses for identifying protein expression patterns are useful technologies to investigate changes in the set of genes expressed in the mammary gland and in the proteome during different physiological stages. These approaches showed that a huge numbers of genes are differentially expressed in mammary epithelial cells during preg-
nancy, lactation, and involution. However, cellular biological approaches through in vivo and dynamic studies are necessary to elucidate the precise links between gene expression and protein synthesis in the mammary gland (Ollivier-Bousquet and Devinoy, 2005). Extensive research on lipid uptake, trafficking, and secretion at the cellular level has been carried out over the last 20 yr. Much of our knowledge has been obtained by studying mechanisms of milk fat depression. In the Hague meeting in 2000, Bauman and Griinari (2001) presented their biohydrogenation theory of milk fat depression involving the concept that rumen biohyrogenation can produce trans-10, cis-12 CLA, which seems to be a potent inhibitor of milk fat synthesis. This concept is supported by data in the cow showing that postruminal infusion of trans-10, cis-12 CLA reduces the abundance in the mammary gland of mRNA for genes involved in fatty acid uptake [i.e., lipoprotein lipase (LPL), fatty acid transport (i.e., fatty acid binding protein; FABP), de novo fatty acid synthesis (i.e., acetylCoA carboxylase; ACC and fatty acid synthase; FAS), desaturation (i.e., stearoyl-CoA desaturase; SCD), and triglyceride synthesis (i.e., acylglycerol phosphate acyl transferase; AGPAT and glycerol phosphate acyl transferase; GPAT)]. Levels of trans-10, cis-12 CLA in milk fat were also found to correlate closely with the decrease in ACC transcript, and less closely, but still significantly, with the reduction in levels of the enzymes FAS, LPL, and GPAT, as recently reviewed by these same authors (Griinari and Bauman, 2006). Another aspect of the regulation of fatty acid profile of milk by the mammary gland relates to unsaturated fatty acids. Desaturase activity in the mammary cells, that introduces a ∆9 double bond in the cis conformation, not only converts stearic acid arising from ruminal biohydrogenation to oleic acid that is secreted in milk, but also is involved in the synthesis of CLA isomers in the mammary gland (Bauman and Griinari, 2001; Chilliard et al., 2001). However, the availability of substrates in the diet is the main factor influencing the content and profile of milk fatty acids, affecting the expression of various lipogenic genes at the level of the mammary gland, as also presented in the latest ruminant physiology symposium in Denmark (Bernard et al., 2006).
MILK AS MEANS OF DELIVERING NUTRIENTS AND BIOACTIVE COMPOUNDS Milk has long been recognized as a source of macroand micronutrients, immunological components, and biologically active substances, which not only allow growth but also promote health in mammalian newborns. At the third BOLFA meeting in Lillehammer in 1996, a workshop section was dedicated to bioactive components of milk (Zinn, 1997). Many milk proteins, lipids, lipid-soluble substances, and their digested products are bioactive, including peptides, triacylglycerols, diacylglycerols, saturated and polyunsaturated fatty
Nutrition in mammary gland health
acids, phospholipids, vitamins, and vitamin-like substances. Milk also contains protein hormones from the anterior pituitary (i.e., prolactin and ST), hypothalamus (i.e., ST releasing hormone and somatostatin) and gut (i.e., vasoactive intestinal peptide, gastrin, and substance P), numerous growth factors (including IGF-I and IGF-II, IGFBP, epidermal growth factor, transforming growth factors), prostaglandins E and F, lactoferrin, and transferrin (Baumrucker and Blum, 1993; Meisel, 1997; Schanbacher et al., 1997; Weaver, 1997; Zinn, 1997). Schanbacher et al. (1997) reviewed the origins of bioactive peptides in milk, their biochemical properties, potential as nutraceuticals, and potential pharmacological applications. For example, lactoferrin is a multifunctional protein involved in immunoregulation, antiinflammation, and especially iron metabolism. The biochemical and other properties of lactoferrin were discussed at the 1998 BOLFA meeting in Denver by Neville et al. (2000). Those authors noted that lactoferrin binding sites have been found in many cell types including intestinal cells, hepatocytes, mammary epithelial cells, and platelets. At the 2004 meeting in Bled, Baumrucker (2005) presented results showing that bovine lactoferrin is involved in the entry of IGFBP-3 into the nucleus of mammary cells. At the 2000 BOLFA meeting in the Hague, the roles of IGF-I and IGFBP in milk were considered by Sejrsen et al. (2001) who noted that colostrum had greater mitogenic activity than did mature milk due to its high IGFI levels; they proposed that the mitogenic activity of colostrum was important for mammary gland development, as well as for the developing neonate. Emphasis at this meeting was also placed on nutritional approaches to alter milk composition for the benefit of human health (Bauman and Griinari, 2001; Chilliard et al., 2001; Clegg et al., 2001). In particular, ways of increasing the polyunsaturated fatty acid content of milk were all considered (Bauman and Griinari, 2001; Chilliard et al., 2001) to thereby produce functional milks. At the most recent BOLFA meeting (2006, Pirassununga, Brazil), the issue of the CLA content of milk was taken up again (da Silva et al., 2006; Paschoal et al., 2006). As noted above, mammary lipogenic gene expression (and hence milk fat synthesis) in cows and goats seems to be regulated by trans fatty acids, with trans-10 C18:1 and trans-10, cis-12 CLA emerging as the main mediators of a milk fat-depressing effect. However, the molecular mechanisms involved in the nutritional regulation of gene expression have not been elucidated completely. Thus, although animal feeding regimens can increase the polyunsaturated lipid content of milk to make it “healthier”, the milk thereby becomes more vulnerable to oxidation, and this stimulated much interest in milk antioxidants and their transfer from dietary components in dairy cows, as reviewed extensively at the seventh BOLFA workshop in Bled (Baldi, 2005; Debier et al., 2005; Meglia et al., 2005).
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In addition to their antioxidant roles that will be discussed in the next section, vitamin E and other fatsoluble vitamins and provitamins (e.g., beta-carotene) are important nutrients per se, for which milk is an important delivery system. Debier et al. (2005) presented results on the roles of vitamins A and E in the early stages of life. Vitamin E is necessary to protect the newborn against oxidative stress, whereas vitamin A is required for growth and development. Both vitamins are essential for immune system development. These vitamins must therefore be provided to neonates in adequate amounts. Colostrum contains relatively high concentrations of vitamins A and E but mature milk contains much less. The transfer of these vitamins into milk does not seem to be simply a passive one associated with lipid transfer. Vitamin supplementation of gestating and lactating animals appears to increase levels of both vitamin E and A in milk and in neonatal serum. However, positive effects on young animals are difficult to document. Studies on seals have shed light on important aspects of the transfer of vitamins A and E from mother to offspring, although much remains to be learned about the metabolism of these vitamins during lactation (Debier et al., 2005). Administration of the natural vs. synthetic form of vitamin E can affect bioavailability and may also influence transfer to milk (Meglia et al., 2005). Like other fat-soluble micronutrients, fat-soluble vitamins are present in the milk fat fraction, and this has important implications for bioaccessibility and bioavailability from milk. In fact, the fat component of milk is a highly effective delivery system for fat-soluble vitamins.
NUTRITION AND MAMMARY GLAND HEALTH The importance of nutrition in maintaining health of the cow during lactation was an important theme throughout all BOLFA workshops and was specifically addressed in the 2004 meeting in Bled. Health may deteriorate during the transition from late pregnancy to lactation in dairy cows. After parturition, nutritional requirements increase rapidly as milk production increase; the negative energy balance period extends for 10 to 12 wk (Butler, 2005). A growing body of evidence indicates that metabolic disorders associated with negative energy balance may impair fertility, immune status, and antioxidant status. During the transition period in dairy cattle, the total antioxidant capacity is most susceptible to be compromised. Higher oxygen demand for milk synthesis and secretion increases the production of reactive oxygen metabolites within the mammary gland. Sordillo (2005) reported that mammary gland cells from periparturient dairy cows produce more cytokines than those from midlactation animals, resulting in transient increases in intracellular reactive oxygen species and indicating that during lactation onset, mammary gland epithelial cells are exposed to significant levels of free radicals. The resulting
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oxidative damage is a possible cause of increased susceptibility to intramammary infection at this time. In such situations, the availability of antioxidants to the mammary cells becomes crucial. The antioxidant system is an integrated system, and deficiencies of one component can affect the antioxidant efficiency of the others. Nutrition has a major influence on balance of prooxidants and antioxidants because several antioxidant system components are micronutrients or are dependent on dietary micronutrients. Vitamin E, betacarotene, and selenium are known to be effective dietary antioxidants in ruminants, whereas several others are under investigation and cannot yet be recommended as routine dietary supplements. In this regard, Baldi (2005) presented results indicating that adequate vitamin E status is important for maintaining health and production in dairy cows. Vitamin E also seems to be crucially involved in immune system function, such that supplementation with supranutritional levels of the vitamin E, in some instances, results in improved immune responses. Vitamin C and other substances (e.g., glutathione and selenium) that are associated with antioxidative defenses, may also be important in maintaining vitamin E status and function and, hence, vitamin E availability at the cellular level. The extent of oxidative stress probably also affects tissue consumption of vitamin E. Although vitamin A does not have all the activities of classical antioxidants, it seems to play a role in mammary gland immunobiology, remodeling, and polymorphonuclear leukocyte function during the peripartum period. In vitro studies of the effect of retinoids on function of polymorphonuclear leukocytes indicate that they directly affect oxidative burst activity and apoptosis, but not chemotaxis (Meyer et al., 2005). Vitamin A also has been suggested to play a role in the morphogenesis, differentiation, and proliferation of the mammary gland. Retinol and retinoic acid have been reported to be potent inhibitors of bovine mammary epithelial cell proliferation in vitro (Cheli et al. 2003). Although the exact mode of action at the cellular level remains unknown, the main protective effects of retinol and retinoic acids may be due to regulatory effects on the growth of normal cells by controlling gene expression of several growth factors. The metabolic health status effects of folate, vitamin B12, and vitamin-like choline also was investigated and it was found that supplies of these micronutrients are not always sufficient to maximize health and productivity of dairy cows. Supplementation, especially during early lactation, can improve lactational performance, metabolic health, and the nutritional quality of milk (Girard and Matte, 2005; Pinotti et al., 2005). However, it also has emerged from these studies that our knowledge of interactions between these 3 micronutrients is incomplete in the dairy cow, and that a nutritional approach based on the supply and utilization of individual nutrients is inadequate, further indicating the need
to reappraise the requirements for B-complex vitamins in dairy cows.
SUMMARY In conclusion, in this review, we have identified major topics about nutrition and lactation in farm animals, as discussed in the BOLFA workshops. Although some of these topics are perennial themes of virtually all BOLFA workshops, it must be emphasized that the methods and approaches used to investigate them have become more sophisticated and powerful over the years, and are expected to develop more rapidly in the future. Genomics, proteomics and related technologies have already emerged important tools for investigating molecular responses to nutrients and their implications for lactation and nutrition in farm animals, exploiting the basic sequence information provided by genome projects.
LITERATURE CITED Baldi, A. 2005. Vitamin E in dairy cows. Livest. Prod. Sci. 98:117–122. Baldi, A., V. Chiofalo, G. Savoini, R. Greco, F. Polidori, and I. Politis. 1997. Changes in plasmin, plasminogen and plasminogen activator activities in milk of late lactating ewes: Effects of bovine somatotropin (bST) treatment. Livest. Prod. Sci. 50:43–44. Bauman, D. E., and J. M. Griinari. 2001. Regulation and nutritional manipulation of milk fat: Low-fat milk syndrome. Livest. Prod. Sci. 70:15–29. Baumrucker, C. R. 2005. Intracrine signaling in the mammary gland. Livest. Prod. Sci. 98:47–56. Baumrucker, C. R., and J. R. Blum. 1993. Secretion of insulin-like growth factors in milk and their effect on the neonate. Livest. Prod. Sci. 35:49–72. Bequette, B. J., F. R. C. Backwell, A. C. Calder, D. E. Beever, J. C. MacRae, and G. E. Lobley. 1994. Use of a mixture of universally 13C-labelled amino acids (AA) to study AA partition to and utilisation by goat mammary gland. Page 10 in 2nd Int. Workshop Biol. Lact. Farm Anim., Minneapolis, MN. Bernard, L., C. Leroux, and Y. Chilliard. 2006. Characterisation and nutritional regulation of the main lipogenic genes in the ruminant lactating mammary gland. Page 295 in Ruminant physiology, digestion, metabolism and impact of nutrition on gene expression, immunology and stress. K. Sejrsen, T. Hvelplund and M. O. Nielsen, ed. Wageningen Academic Publishers, Wageningen, the Netherlands. Boisgard, R., E. Chanat, F. Lavialle, A. Pauloin, and M. OllivierBousquet. 2001. Roads taken by milk proteins in mammary epithelial cells. Livest. Prod. Sci. 70:49–61. Butler, W. R. 2005. Inhibition of ovulation in the postpartum cow and the lactating sow. Livest. Prod. Sci. 98:5–12. Capuco, A. V., S. E. Ellis, S. A. Hale, E. Long, R. A. Erdman, X. Zhao, and M. J. Paape. 2003. Capuco Lactation persistency: Insights from mammary cell proliferation studies. J. Anim. Sci. 81(Suppl.3):18–31. Cheli, F., I. Politis, L. Rossi, E. Fusi, and A. Baldi. 2003. Effects of retinoids on proliferation and plasminogen activator expression in a bovine mammary epithelial cell line. J. Dairy Res. 70:367–372. Chilliard, Y., A. Ferlay, and M. Doreau. 2001. Effect of different types of forages, animal fat or marine oils in cow’s diet on milk fat secretion and composition, especially conjugated linoleic acid (CLA) and polyunsaturated fatty acids. Livest. Prod. Sci. 70:31–48.
Nutrition in mammary gland health Clegg, R. A., M. C. Barber, L. Pooley, I. Ernens, Y. Larondelle, and M. T. Travers. 2001. Milk fat synthesis and secretion: Molecular and cellular aspects. Livest. Prod. Sci. 70:3–14. da Silva, D. C., G. T. dos Santos, P. T. M. Pintro, B. A. Boato, J. B. Visentainer, and H. V. Petit. 2006. Butter quality of Holstein cows fed whole or ground flaxseed with or without monensin. Rivista de Cieˆcias Veterina´rias 4(Suppl.1):30. (Abstr.) Debier, C., J. Pottier, Ch. Goffe, and Y. Larondelle. 2005. Present knowledge and unexpected behaviours of vitamins A and E in colostrum and milk. Livest. Prod. Sci. 98:135–147. Deichsel, K., and J. Aurich. 2005. Lactation and lactational effects on metabolism and reproduction in the horse mare. Livest. Prod. Sci. 98:25–30. Dell’Orto, V., G. Contarini, T. Cattaneo, V. Bontempo, and F. Fantuz. 1994a. Dairy mare’s milk: II. Fat and protein characteristics of milk. Page 11 in 2nd Int. Workshop Biol. Lact. Farm Anim., Minneapolis, MN. Dell’Orto, V., E. Salimei, V. Bontempo, F. Fantuz, P. M. Toppino, G. Contarini, and F. Locci. 1994b. Dairy mare’s milk: I. Yield and composition of milk and relation with some plasma metabolites. Page 11 in 2nd Int. Workshop Biol. Lact. Farm Anim., Minneapolis, MN. Farmer, C., and M. T. Sørensen. 2001. Factors affecting mammary development in gilts. Livest. Prod. Sci. 70:141–148. Flint, D. J., E. Tonner, C. H. Knight, C. B. A. Whitelaw, J. Webster, M. Barber, and G. Allan. 2001. Control of mammary involution by insulin-like growth factor binding proteins: Role of prolactin. Livest. Prod. Sci. 70:115–120. Girard, C. L., and J. J. Matte. 2005. Folic acid and vitamin B12 requirements of dairy cows: A concept to be revised. Livest. Prod. Sci. 98:123–133. Griinari, J. M., and D. E. Bauman. 2006. Milk fat depression: concepts, mechanisms and management applications. Page 389 in Ruminant physiology Digestion, metabolism and impact of nutrition on gene expression, immunology and stress. K. Sejrsen, T. Hvelplund and M.O. Nielsen, ed. Wageningen Academic Publishers, Wageningen, the Netherlands. Hanigan, M. D., B. J. Bequette, L. A. Crompton, and J. France. 2001. Modeling mammary amino acid metabolism. Livest. Prod. Sci. 70:63–78. Hartmann, P. E., N. A. Smith, M. J. Thompson, C. M. Wakeford, and P. G. Arthur. 1997. The lactation cycle in the sow: Physiological and management contradictions. Livest. Prod. Sci. 50:75–87. Jenkins, T. C., and M. A. McGuire. 2006. Major advances in nutrition: Impact on milk composition. J. Dairy Sci. 89:1302–1310. Knight, C. H. 1997. Biological control of lactation length. Livest. Prod. Sci. 50:1–3. Knight, C. H. 2001. Overview of prolactin’s role in farm animal lactation. Livest. Prod. Sci. 70:87–93. Knight, C. H., and C. J. Wilde. 1993. Mammary cell changes during pregnancy and lactation. Livest. Prod. Sci. 35:3–19. McGuire, M. A., J. M. Griinari, D. A. Dwyer, and D. E. Bauman. 1994. response of milk yield and composition to hyperinsulinemic/euglycemic clamp in lactating dairy cows. In 2nd Int. Workshop Biol. Lact. Farm Anim., Minneapolis, MN. Meglia, G., S. K. Jensen, C. Lauridsen, and K. Persson Waller. 2005. Natural or synthetic vitamin E to periparturient dairy cows. Livest. Prod. Sci. 98:182. (Abstr.) Meijer, G. A., and C. J. van der Koelen. 1994. Duodenal infusion of glutamine does not effect milk protein synthesis in late lactation dairy cows. Page 7 in 2nd Int. Workshop Biol. Lact. Farm Anim., Minneapolis, MN. Meijer, G. A., J. Van der Meulen, J. G. Bakker, C. J. Van der Koelen, and A. M. Van Vuuren. 1995. Free amino acids in plasma and muscle of high yielding dairy cows in early lactation. J. Dairy Sci. 78:1131–1141.
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Meijer, G. A., J. van der Meulen, and A. M. van Vuuren. 1993. Glutamine is a potentially limiting amino acid for milk production in dairy cows: A hypothesis. Metabolism 42:358–364. Review. Meisel, H. 1997. Biochemical properties of bioactive peptides derived from milk proteins: Potential nutraceuticals for food and pharmaceutical applications. Livest. Prod. Sci. 50:125–138. Metcalf, J. A., J. D. Sutton, D. E. Beever, and G. E. Lobley. 1994. Short term local infusion of nutrients on mammary metabolism in lactating dairy cows. Page 13 in 2nd Int. Workshop Biol. Lact. Farm Anim., Minneapolis, MN. Meyer, E., I. La Mote, and C. Burvenich. 2005. Retinoids and steroids in bovine mammary gland immunobiology. Livest. Prod. Sci. 98:33–46. Murphy, J. J., and F. O’Mara. 1993. Nutritional manipulation of milk protein concentration and its impact on the dairy industry. Livest. Prod. Sci. 35:117–134. Neville, M. C., and P. Zhang. 2000. Lactoferrin secretion in to milk: Comparison between ruminant, murine, and human milk. J. Anim. Sci. 78(Suppl. 3):26–35. Ollivier-Bousquet, M., and E. Devinoy. 2005. Physiology of lactation: Old questions, new approaches. Livest. Prod. Sci. 98:163–173. Paschoal, J. J., M. A. Zanetti, G. Del Claro, M. P. de Melo, and S. M. P. Pugine. 2006. Effect of extruded soybean and organic selenium on milk composition, conjugated linoleic acid (CLA) concentration, fatty acid profiles and milk oxidation rate. Revista de Cieˆncias Veterina´rias 4(Suppl.1):26. (Abstr.) Pe´rez Laspiur, J., and N. L. Trottier. 2001. Effect of dietary arginine supplementation and environmental temperature on sow lactation performance. Livest. Prod. Sci. 70:159–165. Petitclerc, D., P. Lacasse, C. L. Girard, P. J. Boettcher, and E. Block. 2000. Genetic, nutritional and endocrine support of milk synthesis in dairy cows. J. Anim. Sci. 78(Suppl. 3):59–77. Pettigrew, J. E., J. P. McNamara, M. D. Tokach, R. H. King, and B. A. Crooker. 1993. Metabolic connections between nutrient intake and lactational performance in the sow. Livest. Prod. Sci. 35:137–152. Pinotti, L., A. Campagnoli, V. Dell’Orto, and A. Baldi. 2005. Choline: Is there a need in the lactating dairy cow? Livest. Prod. Sci. 98:149–152. Purup, S., M. Vestergaard, M. S. Weber, K. Plaut, M. R. Akers, and K. Sejersen. 2000. Local regulation of pubertal mammary growth in heifers. J. Anim. Sci. 78(Suppl. 3):36–47. Rulquin, H., P. M. Pisulewski, R. Ve´rite´, and J. Guinard. 1993. Milk production and composition as a function of postruminal lysine and methionine supply: A nutrient-response approach. Livest. Prod. Sci. 37:69–90. Schanbacher, F. L., R. S. Talhouk, and F. A. Murray. 1997. Biology and origin of bioactive peptides in milk. Livest. Prod. Sci. 50:105–123. Sejrsen, K., L. O. Pedersen, M. Vestergaard, and S. Purup. 2001. Biological activity of bovine milk: Contribution of IGF-I and IGF binding proteins. Livest. Prod. Sci. 70:79–85. Sordillo, L. M. 2005. Factors affecting mammary gland immunity and mastitis susceptibility. Livest. Prod. Sci. 98:89–99. Trottier, N. L., and X. F. Guan. 2000. Research paradigms behind amino acids requirements of the lactating sow: Theory and future application. J. Anim. Sci. 78(Suppl. 3):48–58. van Amburgh, M. E., D. M. Galton, D. E. Bauman, and R. W. Everett. 1997. Management and economics of extended calving intervals with use of bovine somatotropin. Livest. Prod. Sci. 50:15–28. Weaver, L. T. 1997. Significance of bioactive substances in milk to the human neonate. Livest. Prod. Sci. 50:139–146. Wilde, C. J., L. H. Quarrie, E. Tonner, D. J. Flint, and M. Peaker. 1997. Mammary apoptosis Livest. Prod. Sci. 50:29–37. Zinn, S. A. 1997. Bioactive components in milk: Introduction. Livest. Prod. Sci. 50:101–103.
