Role of prolactin, growth hormone and insulin-like growth factor 1 in mammary gland involution in the dairy cow

Bovine mammary involution, an important process for subsequent lactations, is characterized by loss of epithelial cells by apoptosis, but its hormonal regulation is still not well defined. Prolactin (PRL) and growth hormone (GH) play a specific role on rat mammary gland apoptosis, through insulin-like growth factor 1 (IGF-1) and the IGF binding protein (IGFBP) system. The purpose of our investigation was to determine the possible role of PRL, GH, and IGF-1 on cell survival and on IGFBP-5 expression in the bovine mammary gland. Mammary gland explants were cultured in the presence of cortisol, 17beta-estradiol, progesterone, insulin, PRL, GH, and IGF-1 and with the same treatment but without PRL, GH or IGF-1, respectively. After 24 h of culture, we determined the level of apoptosis through evaluation of DNA laddering in the oligonucleosomal fraction and examined IGFBP-5 messenger RNA (mRNA) expression. The results show a high level of DNA laddering and an increase in IGFBP-5 mRNA content in mammary explants cultured in the absence of PRL, GH, or IGF-I with respect to explants treated with all hormones. Moreover, explants cultured in presence of PRL, GH, or IGF-I show a low level of DNA laddering and IGFBP-5 expression with respect to explants cultured without any hormones. These data demonstrate a relationship between levels of apoptosis and IGFBP-5 mRNA expression in the bovine mammary gland and confirm the involvement of this binding protein programmed cell death and its relationship with the main lactogenic hormones.     

Abundance and phosphorylation state of translation initiation factors in mammary glands of lactating and nonlactating dairy cows

To test if control of mRNA translation is involved in the increase in protein synthesis by mammary glands during lactation, cellular contents and phosphorylation states of translation factors and their upstream regulators were measured in mammary parenchyma from 12 nonpregnant dairy cows. For a 42-d period, 6 cows in late lactation continued to be milked (L) and 6 at the same stage of lactation were dried off (NL). All cows were then slaughtered and mammary glands and tissue samples obtained. Alveoli and lobules tended to be larger in L cows. Mammary parenchymal mass, cell number, cell size, and RNA, DNA, and protein contents were greater in L cows. Increases (3.1- and 1.8-fold) in the abundance of active, phosphorylated ribosomal protein S6 and its kinase, S6K1, respectively, in L vs. NL parenchyma indicated an ability to sustain greater rates of synthesis of translational machinery, which was also evident in the 102% increase in parenchymal RNA:DNA between the 2 groups. Cellular abundances of the main eukaryotic translation initiation factors (eIF), eIF2 and eIF4E, were 2.6- and 3-fold greater, respectively, in L cows. That these differences were greater than the 102% greater RNA:DNA in L mammary parenchyma suggests an elevated translational efficiency in L glands. Abundance of phosphorylated rpS6 was not different between mammary parenchyma and liver, whereas eIF2α was 50% greater in mammary tissue. In semimembranosus muscle, abundances of phosphorylated rpS6 and eIF2α were 3 to 4 times lower than in mammary parenchyma. In both L and NL mammary glands, 11% of eIF2α was in the inhibitory, phosphorylated form and 48 to 60% of eIF4E was complexed with its binding protein, 4EBP1. It is concluded that up-regulation of initiation of mRNA translation occurs in the fully differentiated milk secretory cell and that, where crucial initiation factors are not present in a maximally active form, the initiation rate might be flexible in response to external stimuli.     

Effects of intramammary infusions of casein hydrolysate,ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid,and lactose at drying-off on mammary gland involution

The transition from the lactation to the dry period in dairy cows is a period of high risk for acquiring new intramammary infections. This risk is reduced when involution of mammary glands is completed. Consequently, strategies that accelerate the involution process after drying-off could reduce the incidence of mastitis. The objective of this study was to assess the effect of 3 different treatments on mammary gland involution. Each quarter of 8 Holstein cows in late lactation was randomly assigned at drying-off to an intramammary infusion of casein hydrolysate (CNH; 70 mg), ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA; 5.7 g), lactose (5.1 g), or saline 0.9% (control) solutions. Milk samples were collected on the last 2 d before and 1, 3, 5, 7, 10, and 14 d after the last milking for determining concentrations of mammary gland involution markers. Lactoferrin, somatic cell counts (SCC), BSA, and Na⁺ concentrations, as well as matrix metalloproteinase-2 and matrix metalloproteinase-9 activities gradually increased in mammary secretions during the first 2 wk following the last milking, whereas milk citrate and K⁺ concentrations decreased. As involution advanced, the Na⁺:K⁺ ratio increased, whereas the citrate:lactoferrin ratio decreased. Compared with mammary secretions from control quarters, mammary secretions of quarters infused with CNH had higher SCC on d 1, 3, 5, and 7, and greater BSA concentrations on d 1, 3, and 5. Similarly, the CNH treatment induced a faster increase in lactoferrin concentrations, which were greater than in milk from control quarters on d 3, 5, and 7 after drying-off. Milk citrate concentrations were unaffected by CNH but the citrate:lactoferrin ratio was lower in CNH-treated quarters on d 3 and 5 than in control quarters. Moreover, CNH treatment hastened the increase in Na⁺ concentration and in the Na⁺:K⁺ ratio on d 1. Infusion of CNH also led to an increase in proteolytic activities, with greater matrix metalloproteinase 9 activities on d 1 and 3. The EGTA infusion increased SCC above that of control quarters on d 1 and 3 but it had no effect on the other parameters. Lactose infusion had no effect on any of the involution markers. In this study, intramammary infusions of CNH were the most efficient treatment to accelerate mammary gland involution, suggesting a potential role of CNH as a local milk secretion inhibitor during milk stasis.     

Efficacy of extended cefquinome treatment of clinical Staphylococcus aureus mastitis

Clinical Staphylococcus aureus mastitis is difficult to cure. Extended antimicrobial treatment is often advocated as a practical approach to improve cure rates; however, scientific evidence of this hypothesis is lacking. A multi-centered, nonblinded, randomized, positive-controlled clinical trial was conducted in 5 European countries—France, Hungary, Italy, the Netherlands, and the United Kingdom—to study the efficacy of an extended intramammary cefquinome treatment (5 d) compared with a standard intramammary cefquinome treatment (1.5 d) of Staph. aureus clinical mastitis. Least squares means estimates of bacteriological cure during lactation were 34% [standard error (SE) = 9.9%] for the standard treatment group and 27% (SE = 8.4%) for the extended treatment group. In the final model, extended therapy was not significantly better. The only factor predicting bacteriological cure was pretreatment cow somatic cell count (SCC). Cows with >250,000 cells/mL in milk before treatment were less likely to cure. Least squares means of clinical cure during lactation was 60% (SE = 19%) for the standard treatment group and 82% (SE = 12%) for the extended treatment group. In the final model, clinical cure after extended treatment was significantly better. Pretreatment cow udder firmness predicted clinical cure. Firm udders were less likely to cure clinically. Irrespective of treatment regimen, new infection rates with pathogens other than Staph. aureus were higher (42%) after bacteriological cure than after nonbacteriological cure (22%) and cured cows had a significantly lower SCC. In conclusion, independent of the treatment protocol, cows with an SCC <250,000 cells/mL before treatment showed a higher probability of bacteriological cure. It appears that successful treatment of clinical Staph. aureus mastitis with cefquinome is associated with an increased number of new infections with coagulase-negative staphylococci. Extended treatment improved clinical, but not bacteriological, cure rates compared with the standard treatment. These results indicate that extending treatment of clinical Staph. aureus mastitis with cefquinome should not be recommended.     

Bovine somatotropin administration to dairy goats in late lactation: effects on mammary gland function,composition and morphology

We investigated the effects of bovine somatotropin (bST) on mammary gland function and composition in the declining phase of lactation in goats. Sixteen Saanen goats, 180 +/- 11 days in milk (DIM), were divided equally into control and treated groups. The treated group received 120 mg/2 wk of slow-release bST for three cycles. Milk yield, milk composition, milk clotting measures, and plasmin-plasminogen activator activities were recorded weekly. Milk Na and K were determined in individual milk samples collected weekly during the third cycle. Blood samples were collected weekly during the second cycle and the plasma analyzed for nonesterified fatty acids (NEFA), glucose, and urea. At the end of the 6 wk, three goats from each group were slaughtered, and the udders were removed. Mammary gland weight, composition, and total DNA content were determined. The histological effects of bST on mammary tissue were investigated. The analyzed parameters included numbers of alveoli, corpora amylacea, apoptotic cells, and laminin fibronectin distribution and localization. An extensive morphological analysis on the epithelial and stromal components was performed. Milk yield was significantly higher in the treated group, fat content was not affected, but protein and nonprotein nitrogen were lower in treated goats milk. Treatment with bST did not influence milk pH but reduced coagulation time. Plasmin and plasminogen activator activities were not affected. Milk K levels were higher and the Na/K ratio was lower in treated animals. Plasma glucose, NEFA, and urea were unaffected. Mammary gland weight and total DNA were higher in treated than control animals, suggesting that with advancing lactation bST treatment maintains cells. Fat, protein, and collagen content of the mammary tissue did not differ between the groups. Treatment with bST significantly increased the number of lactating alveoli (LA) and significantly reduced the number of regressing alveoli (RA) and corpora amylacea, both within and outside the alveolar lumen. Laminin and fibronectin localization were not affected, and very few apoptotic cells were found in both treated and control samples. Our findings suggest that bST administration to dairy goats in late lactation can modulate mammary gland activity and improve lactation persistency; this is associated with maintained total mammary parenchyma weight and lactating alveoli.     

Cell turnover and activity in mammary tissue during lactation and the dry period in dairy cows

Milk yield of the dairy cow follows a pattern termed the lactation curve. We have investigated the cellular background for this pattern. Seven mammary biopsies were obtained from each of 10 cows: at the end of lactation (d 347, equal to d 77 before next parturition); during the dry period at d 48 (4 d after dry off); 16 d before parturition; and during lactation at d 14, 42, 88, and 172. The fraction of proliferating (staining positive for Ki-67) alveolar cells was higher during the dry period (8.6%) than during lactation (0.5%). The fraction of apoptotic (staining positive by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) alveolar cells was higher immediately after dry off (0.37%) and in early lactation (0.76%) than during other periods (0.15%). The enzyme activities of fatty acid synthetase, acetyl CoA-carboxylase, and galactosyl transferase were approximately 12-, 11-, and 4-fold higher, respectively, during lactation than during the dry period. In conclusion, mammary cell proliferation is substantial in a period near parturition but otherwise low, and apoptosis is elevated at dry off and in early lactation. The increase in apoptosis in early lactation may be due to discarding nonfunctional or senescent cells or to removal of a surplus of newly synthesized cells. The activity of selected enzymes central for milk synthesis is probably not limiting for milk production.     

Effects of photoperiod modulation and melatonin feeding around drying-off on bovine mammary gland involution

The risk for a dairy cow to acquire new intramammary infections is high during the transition from lactation to the dry period, because of udder engorgement and altered immune functions. Once the gland is fully involuted, it becomes much more resistant to intramammary infections. Therefore, strategies to depress milk yield before drying-off and accelerate the involution process after drying-off could be beneficial for udder health. The objective of this study was to assess the effect of photoperiod manipulation and melatonin feeding from 14 d before to 14 d after drying-off on the speed of the involution process. Thirty Holstein cows in late lactation were randomly allocated to one of the following treatments: (1) a long-day photoperiod (16 h of light: 8 h of darkness), (2) a short-day photoperiod (8 h of light: 16 h of darkness), and (3) a long-day photoperiod supplemented by melatonin feeding (4 mg/kg of body weight). Milk and blood samples were collected on d ?26, ?19, ?12, ?5, ?1, 1, 3, 5, 7, 10, and 14 relative to the last milking to determine concentrations of mammary gland involution markers and serum prolactin. Additional blood samples were taken around milking on d ?15, before the start of the treatments, and on d ?1, before drying-off, to evaluate the treatment effects on milking-induced prolactin release. The short-day photoperiod slightly decreased milk production and basal prolactin secretion during the dry period. The milking-induced prolactin surge was smaller on d ?1 than on d ?15 regardless of the treatments. Lactoferrin concentration, somatic cell count, and BSA concentration as well as matrix metalloproteinase-2 and -9 activities increased in mammary secretions during the first 2 wk of the dry period, whereas milk citrate concentration and the citrate:lactoferrin molar ratio decreased. The rates of change of these parameters were not significantly affected by the treatments. The long-day photoperiod supplemented by melatonin feeding did not affect milk production, prolactin secretion, or mammary gland involution. Under the conditions in this study, photoperiod modulation and melatonin feeding did not appear to affect the rate of mammary gland involution.     

奶山羊泌乳激素及其受体在乳腺发育过程中的变化规律及作用

探讨奶山羊乳腺发育过程中泌乳激素(E2,P和PRL)及其受体(ERα,PR和PRLR)的变化规律及作用.分别在关中奶山羊乳腺发育的青春期、妊娠期、泌乳期及退化期,采集血清并用放射性免疫学方法测定各激素浓度,采集乳腺组织并用免疫荧光和real-time PCR检测各激素受体表达量.青春期和妊娠早期E2,P和PRL缓慢上升,妊娠晚期E2和P达峰值,泌乳启动PRL高峰,泌乳高峰过后各激素均回复正常水平.ERα和PRLR青春期开始缓慢上升,泌乳启动后ERα达到高峰,而泌乳期PRLR维持在高水平,并在退化期达到表达高峰.青春期PR较妊娠期高,妊娠后期又开始升高,退化期下降.E2与ERα,E2与P及与ERα之间正相关,其余的激素和受体之间相关性不显著.     

Milk production of dairy cows treated with estrogen at the onset of a short dry period

The objective was to determine whether the use of estradiol-17beta (E2) at the initiation of short dry periods prevented an anticipated decline in milk production in the subsequent lactation. Lactating Holstein cows (n = 66) were dried at either 60 or 30 d before expected calving. Treatments in a 2 x 2 factorial arrangement included: D60 (n = 19, 60-d dry, no E2), D60 + E2 (n = 18, 60-d dry, E2), D30 (n = 15, 30-d dry, no E2), and D30 + E2 (n = 14, 30-d dry, E2). To accelerate mammary involution, estradiol-17beta (15 mg in 4 ml of ethanol) was injected subcutaneously daily for 4 d beginning 30 d before expected calving. Parturitions occurred between November 1995, and March 1996. Actual days dry for respective treatments were 57.3, 60.6, 33.9, and 33.8 +/- 1.7 d. Onset of parturition, calving difficulty, and cow health were not affected by E2. Actual 305-d milk yields for the lactation completed immediately before the experimental dry period were 10,318, 10,635, 10,127, and 10,447 +/- 334 kg, respectively; and were 9942, 9887, 9669, and 10,172 +/- 387 kg, respectively, for the lactation immediately following treatment. Respective pre- and posttreatment mature equivalent 305-d yields were 9574, 9861, 9812, and 9724 +/- 297 kg; 8987, 8843, 9126, and 9008 +/- 294 kg. Milk yields did not differ across treatments. Cows with a 34-d dry period were as productive as cows with a 59-d dry period. Estradiol-17beta had no effect, but perhaps should be evaluated with dry periods shorter than 34 d.     

王不留行促进奶牛乳腺泌乳的信号转导途径

应用Western blot检测王不留行水浸提液作用后,乳腺上皮细胞泌乳信号转导基因P-AKT1、cyclinD1、PRLR、P-STAT5a和AMPK、GULT1的变化,结果表明:中药王不留行对P-AKT1、cyclinD1、PRLR、P-STAT5a和AMPK、GULT1基因表达具有一定作用,可能通过mTOR信号转导途径促进乳腺上皮细胞的增殖;通过激活PRLR从而激活Stat5a泌乳信号转导途径激活其下游β-酪蛋白基因的表达;且可能通过激活AMPK而促进GLUT1表达的增强,从而增加细胞对葡萄糖的摄取能力促进乳糖的合成。     

Effect of photoperiod in the third trimester of gestation on milk production and circulating hormones in dairy goats

Multiparous Israeli Saanen goats (n = 8) were blocked at dry off (approximately 45 d prepartum) into 2 treatments of 4 goats each based on body weight (BW), previous milk production, and the number of detected embryos in utero. Treatments consisted of long-day (16 h light:8 h dark) and short-day (8 h light:16 h dark) photoperiods at normothermic ambient temperature (22°C, 72% relative humidity). All goats were returned to ambient photoperiod after kidding, milked twice daily, and milk yield was automatically recorded. Dry matter intake was similar between treatments and averaged 980 g/d. Milk production was greater in the short-day than in the long-day treatment (2,932 vs. 2,320 g/d) during the 12-wk experimental period. Milk protein and lactose contents were similar in both treatments and averaged 3.61 and 4.88%, respectively, whereas milk fat was greater in the long-day treatment (4.80 vs. 4.22%). Plasma insulin-like growth factor 1 was greater in the long-day treatment (149 vs. 73 ng/mL) during the dry period than in the short-day treatment, but was similar postkidding, averaging 76 ng/mL. Concentrations of triiodothyronine in plasma were similar in both treatments during the dry period, but greater during lactation in the short-day treatment (122.1 vs. 94.1 ng/mL). Plasma prolactin was greater in the long-day than in the short-day treatment during the dry period (28.0 vs. 17.5 ng/mL), whereas it was similar throughout lactation (11.7 ng/mL). These data support the idea that greater milk production in goats exposed to short days during the dry period is not explained by differences in feed intake or increased secretion of insulin-like growth factor 1.     

ADSA Foundation Scholar Award: A role for serotonin in lactation physiology—Where do we go from here?

Lactation is a physiological event that is exclusive to mammals. Lactation evolved as a strategy to improve the survival of the young by providing them with the complete nutrition that is required for survival upon birth as well as maternal–offspring bonding. Typically, milk production by the dam matches the demand of the young. The dairy cow is a unique exception in which the discoveries and genetic selection related to lactation physiology have been applied and resulted in a dramatic increase in milk yield of dairy cows. Studies on the role of mammary-derived serotonin and the coordination of various aspects of milk production and maternal metabolism have revealed novel mechanisms by which milk production and maternal metabolism can be improved. Furthermore, the investigation into molecular and cellular mechanisms regulating mammary gland function has revealed the importance of epigenetics on mammary gland function. Understanding mammary gland function at the cellular and physiological levels will be important for improving mammary gland control of maternal metabolism during early lactation. The early lactation period is a critical time for a dairy cow as that is when she is most susceptible to disease and metabolic disorders that can lead to negative effects on her productive capacity and overall health. Our research in the area of serotonin physiology has illustrated the importance of serotonin on the regulation of lactation and maternal homeostasis. Future research in the area of lactation physiology should be targeted at improving maternal health and longevity in the herd through manipulation of the signals the mammary gland sends to coordinate maternal metabolism and synthesize milk. Specifically, we believe that serotonin will play a central role in understanding the communication between the mammary gland and the maternal physiology during lactation.     

Effects of stage of lactation and level of feed intake on energy utilization by Alpine dairy goats

Thirty-six lactating Alpine does were used to determine effects of stage of lactation and level of feed intake on energy utilization. Twelve does were assigned to measurement periods in early, mid, and late lactation (wk 5, 13, and 27, respectively). For 6 does of each group, after ad libitum consumption of a 60% concentrate diet, feed intake was restricted to near the metabolizable energy (ME) requirement for maintenance (ME_m) for 8 d followed by fasting for 4 d. For other does, fasting immediately followed ad libitum consumption. Intake of ME was similar among stages of lactation with ad libitum intake (22.1, 22.1, and 19.8 kJ/d in early, mid, and late lactation, respectively). The efficiency of ME use for maintenance determined with does fed near ME_m averaged 81%. Fasting heat energy was greater for ad libitum consumption than for near ME_m consumption [368 vs. 326 kJ/kg of body weight (BW)^0.75] and was numerically lowest among stages in late lactation with near ME_m intake (334, 350, and 295 kJ/kg of BW^0.75 in early, mid, and late lactation, respectively) and ad libitum consumption (386, 384, and 333 kJ/kg of BW^0.75 in early, mid, and late lactation, respectively). The efficiency of use of dietary ME for lactation was greater for consumption near ME_m than for consumption ad libitum (67.9 vs. 58.6%) and with ad libitum consumption tended to decrease with advancing stage of lactation (63.9, 57.3, and 54.5% for early, mid, and late lactation, respectively). Estimated ME_m was greater for ad libitum intake than for near ME_m intake and was lowest during late lactation (429, 432, and 358 kJ/kg of BW^0.75 for near ME_m intake and 494, 471, and 399 kJ/kg of BW^0.75 for ad libitum intake in early, mid, and late lactation, respectively). However, because of increasing BW as the experiment progressed, ME_m (MJ/d) was similar among stages of lactation with both levels of intake. The efficiency of ME use for maintenance and lactation was similar among stages of lactation and greater with near ME_m intake than ad libitum intake (77.1 vs. 67.7%). In conclusion, the ME_m requirement (kJ/kg of BW^0.75) of does in late lactation was less than in early and mid lactation. A marked effect of restricted feed intake subsequent to ad libitum consumption on estimates of efficiency of energy use for maintenance and lactation was observed compared with use of nonlactating animals. Level of feed intake can have substantial effect on estimates of energy utilization by lactating dairy goats.     

Effects of stage of lactation and dietary concentrate level on energy utilization by Alpine dairy goats

Twenty-four lactating and 13 nonlactating Alpine goats were used to determine effects of stage of lactation and dietary concentrate level on energy utilization. Diets comprising 60 or 20% concentrate (60%C and 20%C, respectively) were consumed ad libitum by lactating animals and at a level of intake near maintenance by nonlactating animals. Measurement periods were d 25 to 31 (early), 87 to 94 (mid), and 176 to 183 (late) of lactation. Eleven observations were made in early and mid lactation for each diet, and 8 and 7 were made in late lactation for the 60%C and 20%C diets, respectively. Efficiency of metabolizable energy (ME) use for maintenance (66.9, 71.4, and 61.1% for early, mid, and late lactation, respectively) and the maintenance ME requirement (479, 449, and 521 kJ/kg of BW^0.75 for early, mid, and late lactation, respectively) determined with nonlactating animals differed among stages of lactation. The efficiency of ME use for maintenance was similar between diets, but the maintenance requirement tended to be greater for the 60%C than for the 20%C diet (504 vs. 463 kJ/kg of BW^0.75). The latter difference may have involved greater ME intake for the 60%C diet, resulting in a slightly greater difference between ME intake and total heat energy for the 60%C compared with the 20%C diet (11 vs. −8 kJ/kg of BW^0.75). Intake of ME by lactating goats was greater for the 60%C than for the 20%C diet (18.6 vs. 16.3 MJ/d). Recovered energy in lactation from mobilized tissue tended to be greater for the 60%C than for the 20%C diet (8.44 vs. 6.55 MJ/d) and differed among stages of lactation (2.60, 1.59, and 1.13 MJ/d in early, mid, and late lactation, respectively). Recovered energy in tissue gain was similar among stages of lactation and between diets and was not different from 0. Efficiency of use of dietary ME for lactation differed among stages of lactation (59.5, 51.9, and 65.4% for early, mid, and late lactation, respectively) and tended to be greater for the 60%C than for the 20%C diet (64.2 vs. 54.9%). The efficiency of use of dietary ME for maintenance and lactation was similar among stages of lactation and was greater for the 60%C compared with the 20%C diet (64.3 vs. 60.9%). Predicted milk yield from National Research Council requirements was reasonably accurate. In conclusion, using data of nonlactating goats to study energy utilization for maintenance in lactation has limitations. Efficiency of energy use by lactating dairy goats consuming diets high in concentrate appears greater than that by goats consuming diets low in concentrate. Despite differences in nutrient requirement expressions, observations of this study support National Research Council recommendations of energy requirements of lactating dairy goats.     

Invited review: Metabolic challenges and adaptation during different functional stages of the mammary gland in dairy cows: Perspectives for sustainable milk production

Milk production of dairy cows has increased markedly during recent decades and continues to increase further. The evolutionarily conserved direction of nutrients to the mammary gland immediately after calving provided the basis for successful selective breeding toward higher performance. Considerable variation in adaptive responses toward energy and nutrient shortages exists; however, this variation in adaptability recently gained interest for identifying more metabolically robust dairy cows. Metabolic challenges during periods of high milk production considerably affect the immune system, reproductive performance, and product quality as well as animal welfare. Moreover, growing consumer concerns need to be taken into consideration because the public perception of industrialized dairy cow farming, the high dependency on feed sources suitable for human nutrition, and the apparently abundant use of antibiotics may affect the sales of dairy products. Breeding for high yield continues, but the metabolic challenges increasingly come close to the adaptational limits of meeting the mammary gland's requirements. The aim of the present review is to elucidate metabolic challenges and adaptational limitations at different functional stages of the mammary gland in dairy cows. From the challenges and adaptational limitations, we derive perspectives for sustainable milk production. Based on previous research, we highlight the importance of metabolic plasticity in adaptation mechanisms at different functional stages of the mammary gland. Metabolic adaptation and plasticity change among developing, nonlactating, remodeling, and lactational stages of the mammary gland. A higher metabolic plasticity in early-lactating dairy cows could be indicative of resilience, and a high performance level without an extraordinary occurrence of health disorders can be achieved.     

Characterization of a changing relationship between milk production and liveweight for dairy goats undergoing extended lactation

This study aimed to characterize the time-profile of extended lactation (EL) for dairy goats, and the relationships between milk production, liveweight, and intake that are associated with this profile. For this, 20 nonpregnant multiparous dairy goats were monitored daily for about 90 d from the onset of EL [i.e., when an increase in milk yield (MY) was observed]. These 20 individual profiles were pooled to create a group average profile at the onset of EL for the purpose of parameterizing a simple compartmental model. Moreover, 9 of the 20 EL goats were kept to compare their 24-mo profiles of body weight and milk production with those observed during 2 successive normal lactations (NL). Despite being kept in the same environment and on the same feed, a clear change from decreasing to increasing MY was identified (time of change, T_change) for all of the 20 EL goats around 330 d in milk. During the whole 24-mo period, EL goats produced as much milk as NL goats but this total milk production was unequally split before (56%) and after (44%) T_change. In terms of body weight, the most striking difference between EL and NL goats was the rapid and very high increase (+9.3 kg with an average daily gain of 60.4 g/d) that was observed concurrently with the increase in MY. Model parameterization with the group average profile does not support that the rise in MY drives the increase in resource acquisition as is generally assumed at the onset of an NL. Rather, it demonstrates that the transfer of energy from feed to milk is delayed at the onset of EL. Moreover, assessing the model ability to fit the range of individual profiles showed that the performances over the first 90 d of EL are largely predetermined by the animal state at T_change. The analysis of individual variability in EL efficiency showed that it depends both on an increase in resource acquisition and on the potential of goats to partition energy from the diet toward milk production instead of to body tissue gain. Finally, predicting the suitability for EL requires the consideration of more than just milk production for 300 d in milk.     

Effects of stage of lactation and dietary forage level on body composition of Alpine dairy goats

Multiparous Alpine does (42) were used to determine how stage of lactation and dietary forage level affect body composition. The feeding and body composition portion of the study had a 2 × 3 factorial arrangement of treatments. Eighteen does were fed a 40% forage diet (40F) and 18 received a diet with 60% forage (60F) for approximately 2, 4, or 6 mo of lactation (59 ± 1.3, 116 ± 1.0, and 184 ± 1.4 d, respectively), followed by determination of body composition (6 does per diet at each time of slaughter). Does were assigned sequentially to treatments as kidding occurred. The 60F diet had 20% more dehydrated alfalfa pellets than the 40F diet, with higher levels of corn and soybean meal and inclusion of supplemental fat in the 40F diet. Initial body composition measures were made with 6 other does a few days after kidding (0 mo; 4 ± 0.6 d). Before parturition, does were fed a 50% concentrate diet free choice. Intake of dry matter was greater for 60F than for 40F, average daily gain tended to be affected by an interaction between diet and month (0, 24, 121, −61, 46, and 73 g), and 4% fat-corrected milk was less in mo 5 to 6 than earlier. Internal fat mass was greatest among times at 6 mo and greater for 40F than for 60F. Mass of the gastrointestinal tract was less for 40F than for 60F and decreased with increasing time in lactation. Concentrations of fat in the carcass (13.8, 13.1, 16.5, 11.2, 11.5, and 14.4%), noncarcass tissues (18.6, 24.2, 33.3, 14.3, 16.5, and 24.5%), and empty body (16.5, 18.7, 25.2, 12.9, 14.1, and 19.5% for 40F at 2 mo, 40F at 4 mo, 40F at 6 mo, 60F at 2 mo, 60F at 4 mo, and 60F at 6 mo, respectively) were affected by stage of lactation and diet. Based on daily change in tissue mass and energy, energy concentration in tissue mobilized or accreted was 16, 20, and 32 MJ/kg in 1 to 2, 3 to 4, and 5 to 6 mo of lactation, respectively. In conclusion, based on tissue mass, more energy was expended by the gastrointestinal tract with 60F than with 40F. Considerable internal fat appeared to be mobilized in early lactation, particularly with the diet moderate to high in forage, with more rapid and a greater magnitude of repletion by does consuming the diet lower in forage. The concentration of energy in tissue mobilized or accreted varied with stage of lactation, being considerably greater at 5 to 6 mo of lactation than earlier.     

Mechanism underlying the modulation of milk production by incomplete milking

Mammary gland secretory activity is modulated by systemic and local factors; however, the relationship between these factors is unknown. The aim of this study was to determine how a local factor, such as incomplete milking, affects mammary epithelial cell activity, number, and responsiveness to blood prolactin (PRL). Eight cows in mid-lactation were differentially milked (i.e., their right quarters were milked incompletely at approximately 70%, and their left quarters were milked completely, twice daily for 4 wk). Throughout the experiment, milk yield was measured at the quarter level. Milk samples were collected from each quarter once a week to assess the milk components, and epithelial cell concentrations, as well as to isolate milk fat globule RNA. In the weeks before and after the experiment, mammary gland functional capacity was evaluated by measuring the volume of milk harvested after complete filling of the gland. At the end of the last experimental week, mammary gland biopsies were performed on each rear quarter. The milk production of quarters milked completely remained stable during the treatment period, whereas, as expected, the milk production of quarters milked incompletely was only 53% of completely milked quarters at the end of the period. Accordingly, the expression of genes related to milk synthesis (CSN2, LALBA, and ACACA) in milk fat was lower in the quarters that were milked incompletely. Incomplete milking decreased the milk lactose content, indicating a loss of integrity of tight junctions. The total yield of epithelial cells in milk was not affected, but their concentration in milk, the BAX:BCL2 gene expression ratio, and the loss of mammary functional capacity were greater in the quarters milked incompletely, suggesting an acceleration of involution in those quarters. The expression of the short isoform of the PRL receptor gene (PRLR) tended to be lower, and the expression of STAT5A and STAT5B tended to decline in the quarters milked incompletely. In mammary gland biopsy samples, the number of both short and long isoforms of the PRLR were not affected, nor were the amount and activation of STAT3 and STAT5. However, the ratio of PRLR short isoform to PRLR long isoform was lower in the quarters milked incompletely. The decrease in milk yield induced by incomplete milking is rapid and associated with a decrease in mammary epithelial cell activity and a decrease in the number of secretory epithelial cells. The results of this experiment provide only limited support for the hypothesis that modulation of the mammary gland's responsiveness to PRL is part of the mechanism by which local factors, such as incomplete milking, modulate milk synthesis.     

Symposium review: The influences of heat stress on bovine mammary gland function

Heat stress reduces cow milk yield and results in a significant economic loss for the dairy industry. During lactation, heat stress lowers milk production by 25 to 40% with half of the decrease in milk synthesis resulting from the reduced feed intake. In vitro studies indicate that primary bovine mammary epithelial cells display greater rates of programmed cell death when exposed to high ambient temperatures, which may lead to a decrease in the total number of mammary epithelial cells in the mammary gland, partially explaining the lower milk production of lactating cows under heat stress. The function of mammary cells is also altered by heat stress. In response to heat stress, mammary cells display higher gene expression of heat shock proteins, indicating a need for cytoprotection from protein aggregation and degradation. Further, heat stress results in increased gene expression without altering protein expression of mammary epithelial cell junction proteins, and does not substantially influence the integrity of mammary epithelium. These data suggest that the mammary gland strives to maintain cell-to-cell junction integrity by synthesizing more proteins to compensate for protein losses induced by heat stress. During the dry period, heat stress negatively affects mammary gland development by reducing mammary cell proliferation before parturition, resulting in a dramatic decrease in milk production in the subsequent lactation. In addition to mammary growth, the mammary gland of the heat-stressed dry cow has reduced protein expression of autophagic proteins in the early dry period, suggesting heat stress influences mammary involution. Emerging evidence also indicates that heifers born to cows that experience late-gestation heat stress have lower milk yield during their first lactation, implying that the maternal environment may alter mammary gland development of the offspring. It is not clear if this is due to a direct epigenetic modification of prenatal mammary gland development by maternal heat stress. More research is needed to elucidate the effect of heat stress on mammary gland development and function.