Genetic parameters of a biological lactation model: early lactation and secretion rate traits of dairy heifers

Early lactation parameters are difficult to estimate from commercial dairy records due to the small number of records available before the peak of production. A biological model of lactation was used with weekly milk records from a single Holstein herd to estimate these early lactation parameters and the secretion rate of milk from the average cell throughout lactation. A genetic analysis of the lactation curve parameters, calculated curve characteristics and secretion rate traits was undertaken. Early lactation traits were found to have little genetic variation and effectively zero heritability. Secretion rate traits for milk, protein, lactose and water were all moderately heritable and highly genetically correlated (>0.87) but fat secretion rate had lower genetic correlations with the other secretion rates. A similar pattern of correlations was seen between total lactation yield traits for fat, protein, lactose and water. The genetic correlations between the lactation curve traits and the secretion rate traits were calculated. Total milk yield, peak yield and maximum secretion potential were all highly correlated with milk, lactose and water secretion rates but less so with fat and protein secretion rates. In particular, fat secretion rate had a moderate to low genetic correlation with these lactation curve traits. Persistency of lactation was highly correlated with fat and protein secretion rates, more persistent lactations being associated with lower rates of secretion of these milk components. Similar levels of heritability were found, where trait genetic parameters were directly equivalent to those derived from the same dataset by random regression methods. However, by using a biological model of lactation to analyse lactation traits new insights into the biology of lactation are possible and ways to select cows on a range of lactation traits may be achieved.     

THE RATE OF DECLINE OF MILK SECRETION WITH THE ADVANCE OF THE PERIOD OF LACTATION

It is shown that the course of decline of milk secretion with the advance of the period of lactation may be expressed by the equation of a monomolecular chemical reaction; that is, the percentage decline of milk secretion with the advance of the stage of lactation is constant. This substantiates the idea that milk secretion is limited by a chemical reaction, and, in general, brings lactation into the class of processes the speed of which is determined by the concentration of a limiting substance.     

Regulation of methyl group metabolism in lactating ewes

The effect of lactation on a number of enzymes involved in transmethylation reactions and the secretion of major methyl compounds into milk have been examined in sheep. The activities of hepatic phospholipid methyltransferase and 5-methyltetrahydrofolate-homocysteine methyltransferase were significantly higher in lactating ewes, compared with those in non-lactating ewes, while the activity of both hepatic and pancreatic glycine methyltransferase was significantly lower in the lactating state. No differences were observed in the activities of hepatic guanidoacetate methyltransferase, betaine-homocysteine methyltransferase and cystathionine beta-synthase on lactation. These results suggest that the extra demand for methyl groups for the secretion of methyl compounds in the milk is facilitated by enhancing the rate of de novo methyl group synthesis and lowering the rate of physiologically nonessential methylation.     

Characterization of milk composition in narrow‐ridged finless porpoises (Neophocaena asiaeorientalis) at different lactation stages

Lactation plays a vital role in reproductive success, evolving with ecological adaptations of mammalian life histories. Knowledge of the lactation process in odontocetes is scarce and limited to a handful of species. We investigated the changes in milk composition across different lactation stages, including prepartum mammary secretion and early, mid‐ and late lactation of narrow‐ridged finless porpoises. Prepartum mammary secretion was greenish and characterized by high protein, low sugar, and negligible fat contents. In contrast, milk fat became predominant over protein and sugar contents throughout all lactation stages. At the early lactation stage, the contents of all milk constituents except water varied greatly. At the mid‐late lactation stage, the gross milk composition was relatively stable and was composed of, on average, 67.34% ± 4.13% water, 9.96% ± 0.75% protein, 21.40% ± 3.24% fat, and 1.72% ± 0.73% sugar. Our findings provide new insight into milk composition at different lactation stages in the narrow‐ridged finless porpoise.     

Cyclic nucleotides in goats' milk: changes with physiological state

Concentrations of cAMP and cGMP were measured in mammary secretions of goats. [cAMP] and [cGMP] increased during late pregnancy. At the onset of copious milk secretion, [cGMP] decreased while [cAMP] increased further. After the cessation of milking in late lactation, [cGMP] increased and [cAMP] tended to decrease. During withdrawal of food for 48 hr, the rate of milk secretion fell, [cGMP] increased and [cAMP] decreased; the changes were reversed on re-feeding. During temporary inhibition of milk secretion by intramammary treatment with colchicine, [cGMP] increased while [cAMP] decreased. It is concluded that cyclic nucleotide concentrations in milk change with physiological state.     

Milk secretion in the rat: progressive changes in milk composition during lactation and weaning and the effect of diet.

1. Progressive changes in the composition of milk from rats has been studied from day 0 to 20 of lactation and for 3 days following separation of the dams and pups at day 20 post partum. 2. The changes in concentration of Na, K and lactose suggested that secretion both prepartum and following weaning occurred by a paracellular mechanism whereas a transcellular pathway existed during established lactation. 3. The concentration of total protein and casein increased gradually throughout lactation. In contrast, the concentration of serum albumin increased and transferrin decreased markedly during early lactation. The fat content of milk declined 3-fold within 5 days of birth but the concentration of Ca, Mg and inorganic P increased. The concentration of each of these milk constituents remained constant during established lactation. 4. Following weaning the pronounced decline in lactose, K and inorganic P was negatively correlated with an increase in all other milk constituents except fat. 5. Rats fed a low energy diet produced milk with a lower fat content but with an unaltered concentration of protein and carbohydrate. The growth rate of these litters was similar for the first 5 days of lactation when compared to litters from dams fed a high energy diet. The growth rate of litters thereafter and following weaning was greater for rats fed a high energy diet.     

Glucose metabolism in crossbred Holstein cattle feeding on two types of roughage at different stages of lactation

An experiment was performed to study the glucose kinetics of crossbred Holstein cattle feeding on either hay or 5% urea-treated rice straw during early lactation (30 days post partum), mid-lactation (120 days post partum) and late lactation (210 days post partum). Two breeds: Holstein FriesianxRed Sindhi (50:50 = 50% HF) and Holstein FriesianxRed Sindhi (87.5:12.5 = 87.5% HF) were used. In early lactating 87.5% HF animals feeding on either hay or urea-treated rice straw, the high milk yields and lactose secretion were related to glucose uptake by the udder and udder blood flow as compared with those of 50% HF animals. Marked decreases in udder blood flow, glucose uptake, lactose secretion and milk yield were apparent in mid- and late lactation of both groups of 87.5% HF animals. In contrast, both groups of 50% HF animals showed no significant changes in udder blood flow, udder glucose uptake, lactose secretion and milk yields throughout the course of lactation. Total glucose entry rate using 3-[3H] glucose infusion, recycling of glucose carbon and plasma glucose clearance significantly increased during late lactation for 50 and 87.5% HF animals feeding on urea-treated rice straw. The utilization rates of glucose using [U-(14)C] glucose infusion were not significantly different among groups of animals and periods of lactation. It can be concluded that 87.5% HF animals have the genetic potential for a higher milk yield, but a shorter peak yield and poorer persistence in comparison with 50% HF animals. Changes in the utilization of glucose by the mammary gland for milk production in both groups of crossbred animals during feeding on either hay or urea-treated rice straw would be dependent on intramammary changes.     

The influence of reproductive experience on milk energy output and lactation performance in the grey seal (Halichoerus grypus)

Although evidence from domestic and laboratory species suggests that reproductive experience plays a critical role in the development of aspects of lactation performance, whether reproductive experience may have a significant influence on milk energy transfer to neonates in wild populations has not been directly investigated. We compared maternal energy expenditures and pup growth and energy deposition over the course of lactation between primiparous and fully-grown, multiparous grey seal (Halichoerus grypus) females to test whether reproductive experience has a significant influence on lactation performance. Although there was no difference between primiparous females in milk composition and, thus, milk energy content at either early or peak lactation primiparous females had a significantly lower daily milk energy output than multiparous females indicating a reduced physiological capacity for milk secretion. Primiparous females appeared to effectively compensate for lower rates of milk production through an increased nursing effort and, thus, achieved the same relative rate of milk energy transfer to pups as multiparous females. There was no difference between primiparous and multiparous females in the proportion of initial body energy stores mobilised to support the costs of lactation. Although primiparous females allocated a greater proportion of energy stores to maternal maintenance versus milk production than multiparous females, the difference was not sufficient to result in significant differences in the efficiency of energy transfer to pups. Thus, despite a lower physiological capacity for milk production, primiparous females weaned pups of the same relative size and condition as multiparous females without expending proportionally more energy. Although reproductive experience does not significantly affect the overall lactation performance of grey seals, our results suggest that increases in mammary gland capacity with reproductive experience may play a significant role in the age-related increases in neonatal growth rates and weaning masses observed in other free-ranging mammals.     

Relationship of milk iron and the changing concentration of mammary tissue transferrin receptors during the course of lactation

The concentration of iron in all mammalian milks falls during lactation while the infant's iron requirement increases. Little is known, however, about the entry of iron into milk. Recently, transferrin receptors have been identified on lactating rat mammary plasma membranes, which may regulate iron entry into mammary tissue, potentiating its availability for subsequent transport into milk. This study was conducted to determine what relationship exists between the declining concentration of milk iron and the transferrin receptor concentration during various stages of lactation. Minimal transferrin receptors were detected in nulliparous rats. Total mammary transferrin receptor content increased during early and mid-lactation while milk iron concentration decreased. The continued appearance of high levels of transferrin receptors throughout lactation, without a concomitant increase in milk iron concentration, suggests a need for iron for functions other than cellular growth or secretion into milk to meet infant needs.     

Sensory stimuli from pups involved in inhibition of milk secretion in rats during late lactation

Lactating rats of two strains, Holtzman and Sprague-Dawley-Rolfsmeyer, were removed from the animal room on postpartum Day 20 and were placed in a testing room where there were no other rats. Milk secretion was stimulated in mothers of each strain 24 hr later in response to 30 min of exposure to a rack of lactators and their pups, placed 3 ft in front of the test mothers; this stimulation to milk secretion was prevented, provided their own pups were placed under, but not when they were placed alongside, the mothers 3–4 min beforehand. The milk secretion responses on the whole were quantitatively less in the Holtzman rats. The sensory signals emanating from the pups which were responsible for the inhibitory effect upon milk secretion were analyzed in Holtzman rats. Sound and odor each proved to be inhibitory; sight, however, was not. The function of the exteroceptive inhibition of milk secretion in the control of milk secretion in late lactation is discussed.     

Secretion of whey acidic protein and cystatin is down regulated at mid-lactation in the red kangaroo (Macropus rufus)

Milk collected from the red kangaroo (Macropus rufus) between day 100 and 260 of lactation showed major changes in milk composition at around day 200 of lactation, the time at which the pouch young begins to temporarily exit the pouch and eat herbage. The carbohydrate content of milk declined abruptly at this time and although there was only a small increase in total protein content, SDS PAGE analysis of milk revealed asynchrony in the secretory pattern of individual proteins. The levels of alpha-lactalbumin, beta-lactoglobulin, serum albumin and transferrin remain unchanged during lactation. In contrast, the protease inhibitor cystatin, and the putative protease inhibitor whey acidic protein (WAP) first appeared in milk at elevated concentrations after approximately 150 days of lactation and then ceased to be secreted at approximately 200 days. In addition, a major whey protein, late lactation protein, was first detected in milk around the time whey acidic protein and cystatin cease to be secreted and was present at least until day 260 of lactation. The co-ordinated, but asynchronous secretion of putative protease inhibitors in milk may have several roles during lactation including tissue remodelling in the mammary gland and protecting specific proteins in milk required for physiological development of the dependent young.     

Influence of torpor on milk protein composition and secretion in lactating bats.

In the pipistrelle bat (Pipistrellus pipistrellus), the metabolic load of lactation is not met to any significant extent by increased food intake or mobilization of body reserves, and aerial foraging accounts for most of the animal's energy expenditure even during lactation. Energy conservation must, therefore, play a critical role in maintaining lactation. The principal mechanism for energy conservation appears to be the bat's ability to enter torpor, but this may itself interrupt milk synthesis and secretion unless the pipistrelle mammary gland is adapted to counteract its effect. The effect of torpor on mammary tissue function was studied in mammary tissue explant cultures prepared in weeks 1-3 of lactation, when milk water yield was 0.20, 0.88, and 0.30 mL/d respectively. Protein synthesis measured by incorporation of radiolabeled amino acids was 44% lower (P < 0.001) in bat tissue explants cultured at ambient temperature (22 degrees C) compared with 37 degrees C. The reduction was similar to that observed in mouse mammary tissue (57%) and was unaffected by stage of lactation. Analysis of explant protein after [35S]methionine labelling showed the majority of proteins synthesised in culture to be milk proteins; it also demonstrated that the decrease in protein synthesis at ambient temperature was a general phenomenon: synthesis of both secretory and intracellular mammary proteins was reduced at the lower culture temperature. The results suggest that bat mammary tissue has no mechanism to counteract the effect of reduced body temperature and that periods of lactational torpor are likely to cause a pronounced diurnal variation in the rate of milk secretion.     

Leptin treatment during lactation increases transfer of iodine through the milk

We have previously shown that protein restriction during lactation is associated with changes in iodine secretion into the milk and that a pup's serum leptin concentration was increased at the end of lactation. So, here we evaluate whether leptin treatment during lactation affects iodine transfer through the milk to the pups. Lactating rats were divided into two groups: the leptin (Lep) group, single injected with recombinant rat leptin (8 microg/100g of body weight, daily for 3 consecutive days), and the control (C) group that received the same volume of saline. We studied iodine transfer to the pups through the milk on Days 4, 12 and 21 of lactation. In those days, the dams were separated from their pups for 4 h. Then, the mothers received an injection of 131I (2.22x10(4) Bq ip) and the pups were allowed to nurse for 2 h. The animals were sacrificed 2 h later. Leptin, total serum T3 and total serum T4 concentrations were higher (P<.05) in pups of Lep mothers only on Day 4, suggesting a higher transfer of leptin through the milk at this period, probably with a direct stimulatory effect on thyroid hormone secretion. In other periods, however, even without a detectable increase in a pup's serum leptin concentration, maternal leptin administration increased the pup's thyroid iodine uptake (Day 12, 39%; Day 21, 34%), probably caused by a higher transfer of iodine through the milk, since they had a higher gastric content of 131I on Days 12 (31%) and 21 (128%).     

Maternal regulation of milk composition,milk production,and pouch young development during lactation in the tammar wallaby (Macropus eugenii )

Specific changes in milk composition during lactation in the tammar wallaby (Macropus eugenii) were correlated with the ages of the developing pouch young (PY). The present experiment was designed to test the hypothesis that the sucking pattern of the PY determines the course of mammary development in the tammar wallaby. To test this hypothesis, groups of 60-day-old PY were fostered repeatedly onto one group of host mothers so that a constant sucking stimulus on the mammary gland was maintained for 56 days to allow the lactational stage to progress 42 days ahead of the age of the young. Analysis of the milk in fostered and control groups showed the timing of changes in the concentration of protein and carbohydrate were essentially unaffected by altering the sucking regime. The only change in milk protein secretion was a small delay in the timing of down-regulation of the secretion of whey acidic protein and early lactation protein in the host tammars. In addition, the rates of growth and development of the foster PY were significantly increased relative to those of the control PY because of ingesting more milk with a higher energy content and different composition than normal for their age. The present study demonstrates that the lactating tammar wallaby regulates both milk composition and the rate of milk production and that these determine the rates of PY growth and development, irrespective of the age of the PY.     

Overexpression of des(1-3) insulin-like growth factor 1 in the mammary glands of transgenic mice delays the loss of milk production with prolonged lactation

During prolonged lactation, the mammary gland gradually loses the capacity to produce milk. In agricultural species, this decline can be slowed by administration of exogenous growth hormone (GH), which is believed to act through insulin-like growth factor 1 (IGF1). Our previous work demonstrated delayed natural mammary gland involution in des(1-3)IGF1-overexpressing transgenic mice (Tg[Wap-des{1-3}IGF1]8266 Jmr), hereafter referred to as WAP-DES mice. The present study tested the hypothesis that overexpressed des(1-3)IGF1 would delay the loss of milk production during prolonged lactation. Accordingly, we examined lactational performance in WAP-DES mice by artificially prolonging lactation with continual litter cross-fostering. Over time, lactational capacity and mammary development declined in both WAP-DES and control mice. However, the rate of decline was 40% slower in WAP-DES mice. Mammary cell apoptosis increased by 3-fold in both groups during prolonged lactation but was not different between genotypes. Plasma concentrations of murine IGF1 were decreased in WAP-DES mice, while those of the transgenic human IGF1 were elevated during prolonged lactation. Phosphorylation of the mammary IGF1 receptor was increased in the WAP-DES mice, but only during prolonged lactation. Plasma prolactin decreased with prolonged lactation in nontransgenic mice but remained high in WAP-DES mice. The WAP-DES mice maintained a higher body mass and a greater lean body mass during prolonged lactation. These data support the conclusion that overexpressed des(1-3)IGF1 enhanced milk synthesis and mammary development during prolonged lactation through localized and direct activation of the mammary gland IGF1 receptor and through systemic effects on prolactin secretion and possibly nutrient balance.     

Prolactin receptors in the brain during pregnancy and lactation: implications for behavior

Numerous studies have documented prolactin regulation of a variety of brain functions, including maternal behavior, regulation of oxytocin neurons, regulation of feeding and appetite, suppression of ACTH secretion in response to stress, and suppression of fertility. We have observed marked changes in expression of prolactin receptors in specific hypothalamic nuclei during pregnancy and lactation. This has important implications for neuronal functions regulated by prolactin. In light of the high circulating levels of prolactin during pregnancy and lactation and the increased expression of prolactin receptors in the hypothalamus, many of these functions may be enhanced or exaggerated in the maternal brain. The adaptations of the maternal brain allow the female to exhibit the appropriate behavior to feed and nurture her offspring, to adjust to the nutritional and metabolic demands of milk production, and to maintain appropriate hormone secretion to allow milk synthesis, secretion, and ejection. This review aims to summarize the evidence that prolactin plays a key role in regulating hypothalamic function during lactation and to discuss the hypothesis that the overall role of prolactin is to organize and coordinate this wide range of behavioral and neuroendocrine adaptations during pregnancy and lactation.     

THE EFFECT OF GESTATION ON THE RATE OF DECLINE OF MILK SECRETION WITH THE ADVANCE OF THE PERIOD OF LACTATION

1. Data are presented showing that the course of decline of milk secretion with the advance of the period of lactation in farrow cows follows the course of decline of a monomolecular chemical reaction, that is each month''s milk production is a constant percentage of the production of the preceding month (94.77 per cent in the case of the cow under consideration), from which it is inferred that milk secretion is limited by a chemical reaction initiated at parturition, and declining with the decrease of the concentration of the limiting substance as it is transformed into milk. 2. Data are presented showing that the decline in milk secretion due to pregnancy is related to the increase in weight of gestating animals, from which it is inferred that growth of the fetus is in part, at least, responsible for the decline in the milk flow due to the demand of the fetus for nutrients to support its life processes.     

Role of milk secretion in transport of prolactin from blood into milk

In a first experiment prolactin was shown to be uniformly distributed in the milk of dairy cows. Accumulation of prolactin in milk increased with milking interval although milk prolactin content was proportionally greater after 2 h than accumulation of milk. Concentration of milk prolactin and total transfer of prolactin into milk was greater in mammary glands of cows milked just prior to initiation of intravenous infusion of exogenous prolactin. Similarly, inhibition of milk secretion as induced by intramammary infusion of colchicine, markedly reduced milk prolactin concentration and total transfer of prolactin into milk 5h following start of intravenous infusion of exogenous prolactin. Data indicate that transfer of prolactin from blood into milk during established lactation occurs primarily in conjunction with milk secretion.