Shaping her future

Shaping her future - the colostrum contribution Fernando Soberon,1 PhD; Melanie A. Soberon,2 PhD ^hur-Gain U.S.A., Strykersville, NY 14145 2Cornell University, Ithaca, NY 14850 Abstract long been valued as critical to new¬ born calf health, but its potential impact on the nutritional programming of the calf and consequently, her lifetime performance in milk production and health, are now areas of active research. New levels of importance and value are being attributed to colostrum, as scientists work to better understand the mechanisms and regulation of epigenetics, the influences of non-nutritional components of colostrum, and the impact of timely colostrum nutrition. Many of these benefits of colostrum were once attributed to passive transfer, but epigenetics and nutritional programming have revealed that there is much more in colostrum than IgG. Relaxin, leptin, insulin, IGF-I, IGF-II, prolactin, and lactoferrin are some of the Colostrum has nutritional and non-nutritional factors in colostrum that have direct and indirect effect on the development and long-term gene expression of offspring. Researchers have shown that calves that received more colostrum at birth have higher av¬ erage daily gains improved feed efficiency, higher dry matter intakes post-weaning, reduced time to conception and first calving, increased milk production during 2 lactations, and an increased survivability through second lactation. a Key words: cattle, calf, colostrum tre nouveaux nes nutritionnel du veau chez les bovins. et done sur la sante et la produc¬ tion de lait durant la vie sont des domaines tout recents de recherche. On attribue maintenant de nouvelles valeurs et plus grande importance au colostrum suite aux percees par des chercheurs sur la regulation et les mecanismes epigenetiques, l’influence des composantes non-nutritionnelles du colostrum et l’impact du moment ou Ton administre le colos¬ une trum. Plusieurs des benefices transfert passif. Toutefois, l'epigenetique et les programmes de nutrition ont montre que les IgG ne sont pas les seuls elements importants dans le colostrum. Plusieurs facteurs nutritionnels et non-nutritionnels du colostrum, leptine, l’insuline, 1’IGF-I, 1'IGF-II, la prolactine et la lactoferrine peuvent avoir un impact direct ou indirect sur le developpement et l'expression a long terme des genes chez la progeniture. Les chercheurs ont montre que les veaux qui recevaient plus de colostrum a la naissance 94 la relaxine, la impact lifelong health, performance, and growth has been a dialogue of great interest throughout history, but with recent scientific assessments and technologies coupled with new observa¬ tions and perspectives, our understanding has increased, and with it, the ability to better quantify and isolate those factors. Colostrum has long been valued as critical to newborn calf health, but its potential impact on the nutritional program¬ ming of the calf and even lifetime performance in milk pro¬ duction and health, are just now receiving recognition. The idea that 1 meal, the first meal of life, can impact an animal for its entire life, generates discussion of how an environmental factor such as nutrition, can alter an animal's genome. The modulation of gene expression through biochemi¬ cal mechanisms that do not alter the DNA sequence but per¬ community as a means development, disease, and performance. Nutritional programming has been reported in multiple species, including insects, birds and mammals, but particu¬ larly in mammals, it provides a mechanism for the mother to continue to influence the development of offspring after birth through her colostrum and milk. This regulation can only oc¬ cur during specific windows of opportunity that, as we better understand, open the possibility to enhance the performance of productive species as well as the possibility to predict and reduce the probability of certain diseases later in life. Epigenetics du colostrum etaient attribues par le passe au comme The conversation of what factors influence and to better understand Neanmoins, l’impact potentiel du colostrum sur le developpement Introduction attention of the medical and scientific depuis longtemps le lien fondamental en- le colostrum et la sante des un manently alter their ability to be transcribed has gained the Resume On reconnait gain moyen quotidien plus eleve, une plus grande efficacite alimentaire, une plus grande prise alimentaire de matieres seches suivant le sevrage, un plus petit intervalle de temps avant la conception et le premier velage, une plus grande production de lait durant les deux premieres lacta¬ tions et une plus grande survie jusqu'a la seconde lactation. avaient of epigenetics is attributed to Conrad Hal Waddington, who in 1953 described epigenetics as an animal's useful response to an environmental stress that persists even after the environmental stress is removed. In some instances, the trait or response becomes permanent in that animal, regardless of the environment.22 Different terms The concept have been used to describe some of the effects controlled through epigenetic mechanisms including imprinting, meta¬ bolic programming, and nutritional programming. Some of THE AABP PROCEEDINGS-VOL. 48 Copyright American Asociatn of Bovine Practiones; open ac es distrbuon. the environmental factors attributed in scientific literature generation of permanent epigenetic changes are tem¬ perature, grooming,24 malnutrition,1215 and overnutrition.9'13 Epigenetics refers to the modification of DNA that re¬ sults in changes in DNA expression but does not change the nucleotide sequence itself. Epigenetic changes are normal, natural phenomena that function through both short-term/ temporary and long-term/permanent changes in gene ex¬ pression. Some of these gene expression regulators can be inherited. Epigenetic mechanisms are used for gene regula¬ tion throughout fetal development, but are not limited to that period of time; normal events such as hibernation, pregnancy, and starvation use epigenetic mechanisms for homeorhesis. Scientists have been particularly interested in those changes to the epigenetic code, also known as the epigenome, that oc¬ cur at 1 specific point in time during development, yet have future phenotypical implications.1'912,13'15'19'24 For example, the amount of grooming a rat received from its mother as a pup has been shown to modify the adult rat's stress response. Pups that were groomed more by their mothers had higher methylation of the first exon of the promoter region for glucocorticoid receptor; this modification persisted for life and resulted in a greater affinity for NGFI-A as an adult rat.24 for the A well-researched event that has further illuminated programming is the famine during the Dutch Hunger Winter. Towards the end of the Second World War, Germany imposed a food restriction on the west¬ ern part of Holland during what proved to be a particularly cold winter. Researchers have used this event to follow up and study the individuals that were conceived or in their mothers' womb during this period. Drastic nutritional restrictions dur¬ ing critical developmental stages in utero led to permanent effects on the methylation of the children’s DNA, and was especially linked to the regulation of IGF-II. Individuals ex¬ posed to the famine during their peri-conception or mother's gestation, exhibited an increased risk for glucose intolerance, impaired insulin secretion, obesity, stress sensitivity, coro¬ nary heart disease, schizophrenia, anti-social behavior, and the effects of nutritional addiction12 later in life. example of nutritional program¬ ming is provided by honey bees. All bees in a hive share the same genetic composition. However, when there is time to produce a new queen, the larva selected to become the queen is fed a 'royal honey'; moreover, it is fed 10 times more than other larvae. This difference in nutrient intake during a criti¬ cal developmental stage changes the epigenome of that 1 bee and instead of becoming a common worker, she grows twice as fast, will have a life expectancy 20 times higher than any other bee, and becomes the only female to develop her female reproductive organs.9 Epigenetics has now been proposed as a potential integral component in future disease diagnosis but equally importantly, it has provided a deeper understanding of the well-known environmental influence on genotypic perfor¬ mance. As more information becomes available, the possibil¬ Another well-studied SEPTEMBER 2015 ity for programming desirable traits in production animals will open a new chapter in animal science and agricultural production. The Traditional Attributes of Colostrum traditionally been recognized as critical for adequate transfer of passive immunity in the newborn calf. It is well documented that calves with <10 mg/mL IgG in blood plasma (5.2 g/dL protein) during the first 2 days of life experienced higher rates of pre-weaning morbidity and mortality.8 In an attempt to explain the effectiveness of colostrum against Escherichia coli infections in the gas¬ trointestinal tract, researchers provided calves with either colostrum followed by E. coli, colostrum combined with E. Colostrum has coli, or E. coli alone. The calves that were administered E. high levels of E. coli attachment in the intes¬ tine as well as E. coli present in the lymph; when colostrum and E. coli were administered simultaneously, there was no attachment of E. coli in the gut, but there were low levels of passive transfer. Finally, when colostrum had been fed prior to the E. coli challenge, there was no bacterial colonization in the gut and high levels of circulating antibodies.23 These IgG benefits of colostrum may last for as long as 3 weeks, but eventually, the calf must depend on its own immune system. While colostrum is a valuable source of immunoglobulins, increasing amounts of literature are suggesting that factors in colostrum other than immunoglobulins are important for long-term productivity and feed efficiency in dairy calves. coli alone had Colostrum Beyond IgGs Proper colostrum administration has consistently been measured through IgG plasma concentration in the calves. Using this assessment, many studies have compared the performance of calves with high low levels of pas¬ sive transfer. This has led to the assumption that IgGs are the cause or promoters of long-term effects associated with feeding proper levels of quality colostrum. However, with new understandings of the potential implications of nutritional programming and its long-term effects, it is now crucial to versus evaluate colostrum for all of its constituents and not restrict passive immunity. The long-term effects reported in scientific literature of feeding an increased quan¬ tity as well as higher quality of colostrum include increased average daily growth up to at least 180 days,17,25 reduced time to first calving,23 and increased milk and fat production dur¬ ing first lactation.711 Most of these studies have sorted calves into different treatment groups based on their IgG plasma concentration; however, a few studies have evaluated the direct effect of quantity of colostrum rather than the passive transfer of IgGs. Using Brown Swiss cattle, Faber et al measured the long-term effects of supplying 4 quarts versus 2 quarts of colostrum during the first feeding. Other than the amount its value to that of 95 Copyright American Asociatn of Bovine Practiones; open ac es distrbuon. of colostrum followed calves were treated the by the feeding of transition milk, all same. Calves that consumed 4 quarts daily gain (ADG) of 0.4 lb (0.18 kg) or 22% greater gain than those calves that received only 2 quarts; there were no significant differences in calving age, but by the end of the calves’ second lactation, the survival rate of calves that had consumed 4 quarts of colostrum was 12% higher (87% vs 75%). Moreover, of the cattle that survived of colostrum had an average end of second lactation, cows that had consumed more to the more milk The amount of colostrum consumed at birth was colostrum at birth produced 2,265 lb (1,029 kg) than those that consumed less colostrum.11 thought to have an interactive effect with the amount of milk or milk replacer (MR) offered during the pre-weaning period. In order to better understand this interaction, Soberon and Amburgh conducted Van calves at were a 2x2 experimental design where offered either 4 quarts or 2 quarts of colostrum birth, after which all calves with an were fed in automatic feeder. Half of the calves treatment replacer commingled on pen each colostrum 12 quarts of milk day and the other half of the calves from each were per a allowed to consume up to quarts per day. Results from this study are presented in Table 1. It is important to highlight treatment were offered 5 for the purpose of this discussion had plasma IgG levels above the that in this study every calf 10 mg/mL, and only 2 out of 125 calves had IgG levels below 12 mg/mL; thus, in any other study, all of these calves would have been considered as having proper passive transfer. When calves were limit-fed 5 quarts per day, ADG pre-weaning, weaning weight, ADG to 80 days, and milk replacer consumption was not significantly different among colostrum treatments. However, when milk replacer was not restricted and calves were allowed to drink sufficient nutrients from milk replacer, calves that received 4 quarts of colostrum had higher ADG pre-weaning, higher weaning weights, higher milk replacer consumption, higher hip height gain by 80 days, and higher ADG post-weaning. In addition, regardless of the milk replacer treatment they were in, calves that consumed 4 quarts of colostrum had higher dry matter intake (DMI) post-weaning compared to calves that consumed only 2 quarts of colostrum.19 The incidence of clinical health events in this study was not different among treatments, which suggests the Weights, heights, average daily gains, and post-weaning dry matter intakes for calves (n = 125) fed either 4 quarts of colostrum and up to 12 quarts of MR (HH), 4 quarts of colostrum and 5 quarts of MR (HL), 2 quarts of colostrum and up to 12 quarts of MR (LH), or 2 quarts of colostrum and 5 quarts of MR (LL). Means and standard deviations shown. Table 1. HH HL LH LL Mean Mean Mean Mean 34 38 26 27 84.3 83.3 82.8 82.8 0.7 97.1 95.8 92.2 95.5 1 31.7 31.6 31.5 31.9 0.6 IgG concentration, mg/dl§ 2,746a 2,480b l,466c l,417c 98 Weaning wt, lb 172.4a 140.0b 159.lc 137.7b 1.9 Weaning hip height, in 36.61a 34.89b 36.04a 35.27b 0.6 pre-weaning (0 to 52 d), lb 1.74a 0.93b 1.48c 0.86b 0 d, lb 1.72a 1.30bc 1.46b 1.17c 0 97.9a 45.2b 90.2C 44.lb 1.2 pre-weaning, lb*5 5.5a 26.5b 4.6a 21.4b 1.5 efficiency pre-weaning1* 0.61 0.61 0.65 0.61 0 Hip height gain, pre-weaning, in/d 0.098a 0.063b 0.091a 0.063b 0 Hip height gain, birth to 80 d, in/d 0.083a 0.063b 0.07T 0.059b 0 Treatment N Days on treatment Birth wt, Birth ADG lb hip height, in ADG birth to 80 Total milk replacer intake, lb DMI§ Grain intake Feed Std dev ADG post-weaning1, lb 2.36a 2.14ab 1.94b 2.03b 0.1 DMI post-weaning*, Ib/d 6.37ab 6.37a 5.69c 5.87bc 0.1 0.33 0.34 0.34 0.36 0 Feed efficiency post-weaning *Data from 5 wk during the pre-weaning period was used in the analysis +DMI includes milk replacer intake and grain intake from birth to weaning ^Measured during 3 weeks after a 1-week adaptation period to pens §Data is only reported for calves in the second block abcValues within the same line with different superscripts differ P < 0.05 96 THE AABP PROCEEDINGS-VOL. 48 ® Copyright American Asociatn of Bovine Practiones; open ac es distrbuon. triggered the increase in performance is more than can be attributed solely to passive transfer. Bartol et al coined a term that is very useful in understanding the possible mechanism working through colostrum; it is the lactocrine hypothesis} mechanism that The Lactocrine Hypothesis hypothesis' attributes the effects of milk-born factors, including colostrum, to the epigenetic development of specific tissues or physiological functions.1 It has been described in multiple species including neonatal pigs, primates, and calves.2,3'4'10'13,15'16 The term was first used by Bartol et al when his group was able to track the direct effects of relaxin found in sow milk on the development of the uterus. They showed an increased reproductive efficiency The 'lactocrine in sows that had been fed colostrum vs formula-fed sows.1 Other evidence for non-nutritional factors present in colostrum was presented by Burrin et al when they examined the effects of feeding colostrum, milk or formula with similar nutrient composition to colostrum to newborn piglets. Piglets that consumed colostrum had higher rates of skeletal protein synthesis as well as higher rates of protein synthesis in the jejunum.5 The evaluation of colostrum intake in calves showed significantly higher plasma levels of glucose in calves fed co¬ lostrum vs formula. This was due to an increased absorptive capacity since the gluconeogenic ability did not differ among the 2 groups of calves.20 These results were further supported by an increased glycogen concentration in liver in colostrumfed calves. Researchers also tested calves after a 15-hour feed deprivation period and observed that colostrum-fed calves had higher levels of circulating glucose and lower plasma urea concentrations, indicating lower levels of protein catabolism in colostrum-fed calves.20 previously mentioned in this paper ob¬ served by Faber et al in Brown Swiss and those described by Soberon and Van Amburgh using Holstein calves that were fed either 2 or 4 quarts of colostrum at birth are most likely explainable through the lactocrine hypothesis, where non-nutritional factors present in colostrum might be re¬ sponsible for the increase in feed efficiency, increased DMI, increased average daily growth, increase in milk production, The effects and increased survival. There these effects might be directly attributed to nutrient intake; this hypothesis is sup¬ ported by data from Soberon et al that suggests that long-term effects such as increased milk production are a consequence more related to nutrient intake and pre-weaning growth rates than a single milk-born factor.18 In most cases, the studies that support nutrient intake as the main factor for increased future productivity analyzed differences in intake during the first 30 to 60 days of life; therefore, the question remains as are others that suggest to the interaction of both nutrient intake levels and non- SEPTEMBER 2015 given that each are provided within the right window of time or at the proper developmental stage. nutritional factors, Last Remarks on Colostrum highly concentrated source of nutrients and non-nutritional factors that are produced by the periparturient dam to be the first feed their progeny consumes. Colostrum, when compared to milk, is higher in fat (6.7% vs 3.7%), total protein (14% vs 3.2%), and IgG (3.2 vs 0.06 g/100 mL). Even though it is impressive to have 60 times more IgGs in colostrum than in milk, there is 155 times more Colostrum is a IGF-I in colostrum than in milk. Colostrum also contains 18 prolactin, 100 times more insulin, 90 times more leptin, and 19 times more relaxin than milk. These are only a few of the non-nutritional factors that may have long-term implications in the development of newborn calves. times more Conclusions traditionally been valued for the passive transfer that it provides to calves. Although passive transfer Colostrum has valuable attribute of colostrum, it is now known that other factors present in colostrum, not directly related to is a on the future of calves. Non-nutritional factors in colostrum performance are potential factors influencing the epigenome of newborn calves. The benefits of providing 4 quarts of colostrum within the first hour of birth have been observed to include improvements in ADG, increased DMI, reduced time to first breeding, reduced time to first calving, increased milk production, and increased survivability to second lactation. Colostrum is still important for passive transfer of immunity but its long-term benefits add to its value, making colostrum the 1 most important step in shaping the future of dairy cows. immunity, have a great impact Reference 1. Bartol FF, endometrial Wiley AA, Bagnell CA. Epigenetic programming of porcine function and the lactocrine hypothesis. Reprod Domest Anim 2008; 43:273-279. CR, Blum JW. Secretion of insulin-like growth factors in milk and their effect on the neonate. Livest Prod Sci 1993; 35:49-72. 2. Baumrucker JW, Hammon H. Colostrum effects on the gastrointestinal tract, and on nutritional, endocrine and metabolic parameters in neonatal calves. Livest Prod Sci 2000; 66:151-215. 4. Burrin DG, Davis TA, Ebner S, Schoknecht PA, Fiorotto ML, Reeds PJ. Colos¬ 3. Blum trum enhances the nutritional stimulation of vital organ in neonatal pigs./Nutr 1997; 127:1284-1289. protein synthesis 5. Burrin, DG, Davis TA, Ebner S, Schoknecht PA, Fiorotto ML, Reeds P], McA- voy S. Nutrient-independent and nutrient-dependent factors stimulate pro¬ tein synthesis in colostrum-fed newborn pigs. PediatrRes 1995; 37:593-599. Corley LD, Staley TE, Bush LJ, Jones EW. Influence of colostrum on transepithelial movement of Escherichia coli 055./Dairy Sci 1977; 60:1416-1421. 7. DeNise SK, Robison JD, Stott JH, Armstrong DV. Effects of passive immunity on subsequent production in dairy heifers. J Dairy Sci 1989; 72:552-554. 8. Dewell RD, Hungerford LL, Keen JE, Grotelueschen DM, Rupp GP, Griffin DD. Health and performance effects of inadequate colostral transfer in beef calves. Proceedings. 35th Annu Conf Am Assoc Bov Pract 2002; 168. 6. 97 © Copyright American Asociatn of Bovine Practiones; open ac es distrbuon. MJ, Kucharskib R, Maleszkab R, Hurd PJ. Extensive histone posttranslational modification in honeybees. Insect Biochemistry and Molecular Biology 2013; 43:125-137. 10. Donovan SM, Odle J. Growth factors in milk as mediators of infant devel¬ opment. Annu Rev Nutr 1994; 14:147-167. 11. Faber SN, Faber NE, McCauley TC, Ax RL. Case study: effects of colostrum ingestion on lactational performance. ProfAnim Sci 2005; 21:420-425. 12. Heijmansa BT, Tobia EW, Steinb AD, Putterc H, Blauwd GJ, Sussere ES, Slagbooma PE, Lumey LH. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proceedings. National Academy of 9. Dickmana Science 2008; 105:17046-17049. Capitanio JP. Lactational programming? Mother’s milk energy predicts infant behavior and temperament in rhesus macaques (Macaca mulatto). Amer J Primatology 2010; 72:522-529. 14. Moallem U, Werner D, Lehrer H, Kachut M, Livshitz L, Yakoby S, Shamay A. Long-term effects of feeding ad libitum whole milk prior to weaning and prepubertal protein supplementation on skeletal growth rate and firstlactation milk production./Dairy Sci 2010; 93:2639-2650. 15. Nusser KD, Frawley S. Depriving neonatal rats of milk from early lacta¬ tion has long-term consequences on mammotrope development. Endocrine 13. Hinde K, 1997; 7:319-323. 16. Rauprich AB, Hammon HM, Blum JW. Influence of feeding different amounts of first colostrum on metabolic, endocrine, and health status and growth performance of neonatal calves.] Anim Sci 2000; 78:896-908. 17. Robison JD, Stott GH, DeNise SK. Effects of passive immunity on growth and survival in the dairy heifer./Dairy Sci 1988; 71:1283-1287. on Raffrenato E, Everett RW, Van Amburgh ME. Early life milk replacer intake and effects on long term productivity of dairy calves./ Dairy Sci 2012; 95:783-793. 19. Soberon F, Van Amburgh ME. Effects of colostrum intake and pre-weaning 18. Soberon F, post-weaning feed efficiency and voluntary feed intake./ Dairy Sci 2011; 94:69-70 (Abstr.J. 20. Steinhoff-Wagner J, Gors S, Junghans P, Bruckmaier RM, Kanitz E, Metges nutrient intake on CC, Hammon HM. Intestinal glucose absorption but not endogenous glucose production differs between colostrum- and formula-fed neonatal calves./ Nutr 2011; 141:48-55. Tejero C, Bach A. Long-term effects on heifer performance of an enhanced growth feeding program applied during the pre-weaning period. J Dairy Res 2009; 76:331-339. 22. Waddington CH. Genetic assimilation of an acquired character. Evolution 21. Terre M, 1953; 7:118-126. early calfhood at first calving. Can J Vet Res 1986; 23. Waltner-Toews D, Martin SW, Meek AH. The effect of health status on 50:314-317. survivorship and age Champagne FA, D'Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ. Epigenetic programming by maternal behavior. Nat Neurosci 2004; 7:847-54. Epub 2004 Jun 27. 25. Wittum TE, Perino LJ. Passive immune status at post-partum hour 24 and long-term health and performance of calves. Am J Vet Res 1995; 24. Weaver 1C, Cervoni N, 56:1149-1154. Copyright American Asociatn of Bovine Practiones; open ac es distrbuon. 98 THE AABP PROCEEDINGS—VOL 48