Mammary cell number, proliferation, and apoptosis during a bovine lactation: relation to milk production and effect of bST.

This investigation evaluated mammary cell loss and replacement during lactation and the impact of administration of bST on these processes. During lactation, a gradual decrease in number of mammary epithelial cells within the mammary glands occurs and largely accounts for the decline in milk production with advancing lactation. This decrease is not appreciably impacted by the loss of viable epithelial cells in milk. Rather, the net decline in cell number (approximately 50% during the entire lactation) results from continual death by apoptosis. Accompanying the decline in mammary cell number by apoptosis is a degree of cell renewal. Approximately 0.3% of mammary cells in lactating, nonpregnant cows were labeled by a 24-h in vivo treatment with the thymidine analog, bromodeoxyuridine. During the entire lactation, the number of new cells amounts to approximately 50% of the number of cells initially present. By the end of lactation, most cells present in the mammary gland were formed after calving. Increasing cell replacement or decreasing apoptosis during lactation may provide a means to increase persistency of lactation. Indeed, administration of bST to Holstein cows during midlactation increased the proportion of mammary epithelial cells expressing the nuclear proliferation antigen, Ki-67, from 0.5 to 1.6%. Bovine somatotropin appears to increase the rate of cell renewal in the lactating mammary gland. Knowledge of molecular regulation of apoptosis and cell proliferation should provide a means to modulate cell turnover in the mammary gland. A change in the ratio of epithelial proliferation to cell death during lactation will affect the persistency of lactation.     

Ovariectomy improves lactation persistency in dairy cows

A current trend in the dairy industry is to reduce milk yield at the peak of lactation and improve lactation persistency. Lactation persistency is influenced by livestock management factors, such as feeding level or milking frequency, or by physiological status, including reproductive status or calving period. These factors modulate mammary gland apoptosis and tissue remodeling, which determine the rate of decline of milk yield after the lactation peak. Previous studies on lactating cows suggested that ovarian steroids have a negative effect on milk yield after the peak of lactation. In the present study, 4 Holstein × Normande crossbred multiparous cows were ovariectomized at the time of the lactation peak, and 5 cows underwent sham operations. All of the cows were maintained in lactation for 14 mo and milk yield was recorded daily. At slaughter, mammary epithelial cell apoptosis and mammary tissue remodeling were assessed. Ovariectomized cows had improved lactation persistency and presented an average daily milk gain of 2.5 kg compared with the sham-operated cows between mo 6 and 14 of lactation. The ovariectomy appears to have limited the decline in the milk yield after the peak of lactation by reducing mammary epithelial cell apoptosis [by reducing poly(adenosine diphosphate-ribose) polymerase expression] and mammary-tissue remodeling (by reducing matrix metalloproteinase activity). In conclusion, removal of ovarian secretion via ovariectomy improved the cows' lactation persistency.     

Mammary growth during lactation: implications for increasing milk yield

Milk yield is greatly influenced by the size of the mammary secretory cell population. In rats, proliferation of cells during early lactation may account for as much as three-quarters of the increase in daily milk yield between parturition and peak lactation; the remainder is due to increased activity of existing cells. Conversely, in goats, all the initial decline in milk yield after peak lactation can be attributed to loss of secretory cells. Increased frequency of milking enhances milk yield and reduces secretory cell loss, whereas goats hemimastectomized at peak lactation undergo compensatory changes in the remaining gland, which include a complete maintenance of cell number for at least 18 wk. Cell proliferation is increased in both cases, showing that mammary growth can occur during established lactation. The significance of this observation is discussed in relation to ways in which the milk yield of dairy animals might be increased.     

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.     

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.     

Regulation of mammary glucose uptake in goats: role of mammary gland supply, insulin, IGF-1 and synthetic capacity.

Variations in mammary glucose uptake were measured during the normal pregnancy-lactation cycle in dairy goats. In addition mammary glucose uptake was studied in response to somatotropin (ST) treatment in mid-lactation and acute increases in glucose concentration induced by sodium-propionate challenge in early lactation. Mammary glucose uptake was independent of arterial glucose, insulin and Insulin-like Growth Factor-1 (IGF-1) concentrations during lactation and during acute increases in arterial glucose concentration. Glucose uptake in the lactating mammary gland of the goat must therefore be carried out by an insulin-independent carrier, possible GLUT1, and glucose supply is not a limiting factor for uptake under in vivo conditions. Extraction of glucose uptake changed markedly during the normal course of lactation, following the overall changes in milk yield. Concentrations of glucose in skimmed milk, believed to reflect intracellular glucose concentration, changed in opposite directions, resulting in decreasing ratios of arterial: skimmed milk glucose concentration with progressing lactation. Thus, mammary synthetic capacity also involves a capacity for glucose uptake, which may be influenced by variations in glucose carrier numbers, as well as mammary metabolic activity (intracellular glucose concentration). In contrast to the situation during the normal course of lactation, ST stimulated milk yield, despite less efficient glucose extraction.     

Mammary gland function during involution

The process of mammary gland involution occurs during the transition from a lactating to a nonlactating state. This transition phase begins after cessation of milk removal and results in changes in mammary secretion composition. Secretion volume declines during involution, as does the concentration of most milk-specific components. Lactoferrin, hydrolytic enzymes, immunoglobulins, and serum-derived components increase in concentration in the secretions during involution. Changes in mammary secretion composition may reflect changes in function of alveolar epithelial cells and have implications for the disease resistance of the gland. Histological and ultrastructural changes occurring in the gland are consistent with a decline in secretion of milk components from epithelial cells. Autophagocytic mechanisms may be involved in this decline in the lactation function. Ultrastructurally, there is little evidence for an extensive loss of epithelia in the bovine mammary gland during involution. Completion of the functional changes occurring in the gland during the process of involution may be required for the gland to redevelop fully for maximal milk yield in the subsequent lactation. Cellular mechanisms involved in mammary involution and relationships between the processes of involution and redevelopment should be areas of particular interest in the mammary function of dairy cattle.     

A biological approach to lactation curve analysis for milk yield

Lactation records of milk yield are commonly analyzed with empirical mathematical models. A family of new models is described based on the known biology of the mammary gland during pregnancy and lactation. The new models fit two logistic curves representing secretory cell differentiation and cell death (apoptosis) throughout lactation. A further function describes secretion rate changes. Both additive and multiplicative forms of the new models are described. Additional terms in the model can account for factors that alter the course of milk yield during the lactation, either by new cell differentiation, a change in the rate of milk secretion loss, or both. The new models were compared with three widely used empirical functions and another biologically based function using weekly records of milk yield taken from 40 dairy cows. The new models fitted the data with a lower residual mean square than the other functions. In addition, the parameters of the new models have a biological interpretation and can be used to discuss key characteristics of lactation. The application of the new models to monthly lactation records is possible, although a reduction in the number of parameters is likely to be required. Some parameters in the cell differentiation function of the models will be poorly estimated from monthly records and can be replaced with average or standard values.     

Metabolic and hormonal control of energy utilization and partitioning from early to mid lactation in Sarda ewes and Saanen goats

In a recent study, we observed that starch-rich diets used in mid lactation induced lower milk production persistency and higher body fat accumulation in dairy ewes compared with dairy goats. Because these species differences could be linked to hormonal mechanisms that drive energy partitioning, in the same experiment, we explored the evolution of metabolic and hormonal status during lactation to test this hypothesis. Twenty mature Sarda dairy ewes and 20 mature Saanen goats [15–134 ± 11 d in milk (DIM), mean ± SD] were compared simultaneously. In early lactation, each species was allocated to one dietary treatment: high-starch diet [HS: 20.4% starch, on dry matter (DM) basis], whereas from 92 ± 11 DIM, each species was allocated to 1 of 2 dietary treatments: HS (20.0% starch, on DM basis) and low-starch (LS: 7.8% starch, on DM basis) diets. Blood samples were collected in the morning to analyze glucose, nonesterified fatty acids (NEFA), growth hormone (GH), insulin, and insulin-like growth factor I (IGF-I). Data were analyzed using the PROC MIXED procedure of SAS with repeated measurements (SAS Version 9.0). The HS and LS diets applied in mid lactation did not affect metabolic status of the animal within species; thus, only a comparison between species was carried out. From early to mid lactation, plasma glucose concentration was higher in ewes than in goats (54.57 vs. 48.35 ± 1.18 mg/dL), whereas plasma NEFA concentration was greater in goats than in ewes (0.31 vs. 0.25 ± 0.03 mmol/L). Goats had higher plasma GH concentration and lower plasma insulin content than ewes (4.78 vs. 1.31 ng/mL ± 0.47; 0.11 vs. 0.26 μg/L ± 0.02). Plasma IGF-I concentration did not vary between species. The comparison of metabolic and hormonal status of lactating Sarda dairy ewes and Saanen goats, carried out by studying simultaneously the 2 species in the same stage of lactation and experimental conditions, suggests that the higher insulin and glucose concentration observed in Sarda ewes explains why they partitioned more energy toward body reserves than to the mammary gland, especially in mid lactation. This can justify the negative effect of high-starch diets in mid-lactating Sarda ewes. Conversely, the highest GH and NEFA concentration observed in Saanen goats explain why they partitioned more energy of starch diets toward the mammary gland than to body reserves and justify the positive effect of high-starch diet in mid lactation. Together, these different responses contribute to explain why specialized dairy goats, such as the Saanen breed, have a higher milk production persistency than specialized dairy sheep breeds, such as the Sarda.     

Pattern of eprinomectin milk excretion in dairy sheep unaffected by lactation stage: comparative residual profiles in dairy products

Eprinomectin (EPM) is a broad-spectrum endectocide compound approved for use in dairy cattle with a zero milk-withdrawal period, but has not been registered for use in lactating dairy sheep. The pattern of EPM excretion in milk was comparatively characterized following its pour-on administration (500 microg/kg) to lactating dairy sheep at two different stages of lactation. The relationship between milk excretion and plasma disposition kinetics of EPM was characterized. Residual EPM concentrations were assessed during cheese making (whey and curd) and ripening (cheese) by high-performance liquid chromatography and fluorescence detection. EPM was poorly distributed from the bloodstream to the mammary gland and low concentrations were excreted in milk. The level of milk production (early-mid and mid-late lactation) did not affect either the plasma-milk distribution or the pattern of residual concentrations in milk. During cheese making, the highest residual concentrations of EPM were measured in the curd, which increased during cheese ripening, reaching a maximum after 40 days. However, these residual concentrations were below the maximum residue limit of 20 ng/ml established for EPM in bovine's milk. Therefore, these dairy products could be considered safe for consumers after the EPM antiparasitic pour-on treatment (500 microg/kg) in lactating dairy sheep.     

Invited review: Palmitic and stearic acid metabolism in lactating dairy cows

Energy is the most limiting nutritional component in diets for high-producing dairy cows. Palmitic (C16:0) and stearic (C18:0) acids have unique and specific functions in lactating dairy cows beyond a ubiquitous energy source. This review delineates their metabolism and usage in lactating dairy cows from diet to milk production. Palmitic acid is the fatty acid (FA) found in the greatest quantity in milk fat. Dietary sources of C16:0 generally increase milk fat yield and are used as an energy source for milk production and replenishing body weight loss during periods of negative energy balance. Stearic acid is the most abundant FA available to the dairy cow and is used to a greater extent for milk production and energy balance than C16:0. However, C18:0 is also intimately involved in milk fat production. Quantifying the transfer of each FA from diet into milk fat is complicated by de novo synthesis of C16:0 and desaturation of C18:0 to oleic acid in the mammary gland. In addition, incorporation of both FA into milk fat appears to be limited by the cow’s requirement to maintain fluidity of milk, which requires a balance between saturated and unsaturated FA. Oleic acid is the second most abundant FA in milk fat and likely the main unsaturated FA involved in regulating fluidity of milk. Because the mammary gland can desaturate C18:0 to oleic acid, C18:0 appears to have a more prominent role in milk production than C16:0. To understand metabolism and utilization of these FA in lactating dairy cows, we reviewed production and milk fat synthesis studies. Additional and longer lactation studies on feeding both FA to lactating dairy cows are required to better delineate their roles in optimizing milk production and milk FA composition and yield.     

The effects of L-type amino acid transporter 1 on milk protein synthesis in mammary glands of dairy cows

The mammary gland requires the uptake of AA for milk protein synthesis during lactation. The L-type amino acid transporter 1 (LAT1, encoded by SLC7A5), found in many different types of mammalian cells, is indispensable as a transporter of essential AA to maintain cell growth and protein synthesis. However, the function of LAT1 in regulating milk protein synthesis in the mammary gland of the dairy cow remains largely unknown. For the current study, we characterized the relationship between LAT1 expression and milk protein synthesis in lactating dairy cows and investigated whether the mammalian target of rapamycin complex 1 (mTORC1) signaling controls the expression of LAT1 in their mammary glands. We found that LAT1 and the heavy chain of its chaperone, 4F2, were expressed in mammary tissues of lactating cows, with the expression levels of LAT1 and the 4F2 heavy chain being significantly greater in lactating mammary tissues with high-milk protein content (milk yield, 33.8 ± 2.1 kg/d; milk protein concentration >3%, wt/vol,; n = 3) than in tissues from cows with low-milk protein content (milk yield, 33.7 ± 0.5 kg/d; milk protein concentration <3%, wt/vol; n = 3). Immunofluorescence staining of sectioned mammary tissues from cows with high and low milk protein content showed that LAT1 was located on the whole plasma membrane of alveolar epithelial cells, suggesting that LAT1 provides essential AA to the mammary gland. In cultured mammary epithelial cells from the dairy cows with high-milk protein content, knockdown of LAT1 expression decreased cell viability and β-casein expression; in contrast, overexpression of LAT1 had the opposite effect. Inhibition of mTORC1 by rapamycin attenuated the phosphorylation of molecules related to mTORC1 signaling and caused a marked decrease in LAT1 expression in the cultured cells; expression of β-casein also decreased significantly. These results suggest that LAT1 is involved in milk protein synthesis in the mammary glands of lactating dairy cows and that the mTORC1 signaling pathway might be a control point for regulation of LAT1 expression, which could ultimately be used to alter milk protein synthesis.     

The tammar wallaby and fur seal: models to examine local control of lactation

Mammary development and function are regulated by systemic endocrine factors and by autocrine mechanisms intrinsic to the mammary gland, both of which act concurrently. The composition of milk includes nutritional and developmental factors that are crucial to the development of the suckled young, but it is becoming increasingly apparent that milk also has a role in regulating mammary function. This review examines the option of exploiting the comparative biology of species with extreme adaptation to lactation to examine regulatory mechanisms that are present but not readily apparent in other laboratory and livestock species. The tammar wallaby has adopted a reproductive strategy that includes a short gestation (26 d), birth of an immature young, and a relatively long lactation (300 d). The composition of milk changes progressively during the lactation cycle, and this is controlled by the mother and not the sucking pattern of the young. Furthermore, the tammar can practice concurrent asynchronous lactation; the mother provides a concentrated milk high in protein and fat for an older animal that is out of the pouch and a dilute milk low in fat and protein but high in carbohydrates from an adjacent mammary gland for a newborn pouch young. This phenomenon suggests that the mammary gland is controlled locally. The second study species, the Cape fur seal, has a lactation characterized by a repeated cycle of long at-sea foraging trips (up to 28 d) alternating with short suckling periods of 2 to 3 d ashore. Lactation almost ceases while the seal is off shore, but the mammary gland does not progress to apoptosis and involution, most likely because of local control of the mammary gland. Our studies have exploited the comparative biology of these models to investigate how mammary function is regulated by endocrine factors, and particularly by milk. This review reports 3 major findings using these model animals. First, the mammary epithelial cell has an extraordinary intrinsic capacity for survival in our culture model, and the path to either function or death by apoptosis is actively driven. The second outcome is that the route to apoptosis is most likely regulated by specific milk factors. Finally, whey acidic protein, a major milk protein in some species, may play a role in normal mammary development, but that role in vivo may be limited to marsupials. Evolutionary pressure has led to changes in the structure of the protein with an accompanying change in function. Therefore, we propose that a loss of function of this protein in eutherians may relate to a reproductive strategy that is less dependent on lactation.     

Short communication: suppression of estrous cycles in lactating cows has no effect on milk production

The decline in milk yield observed after peak production in dairy animals results from apoptotic death of mammary epithelial cells. In cows, this decrease in milk yield can be accelerated by injection of 17β-estradiol, thus evoking a possible role of estrogens in the regulation of bovine mammary gland involution. In nonpregnant cows, mammary involution could be induced or enhanced by the return of estrous cycles and the accompanying cyclic peaks of estrogen concentration in the serum of lactating animals. To test this hypothesis, we inserted implants of a GnRH agonist, deslorelin, in an ear of each cow (n = 10) on d 10 and 100 of lactation, to temporarily suppress the return of ovarian cycles. Cows were studied from calving to d 210 of lactation. Deslorelin had no impact on feed intake or animal health. Deslorelin significantly reduced serum concentrations of 17β-estradiol and progesterone as compared with untreated cows (n = 10). Deslorelin had no effect on milk fat and protein, whereas milk lactose content was lower in treated cows than in control cows on d 100 of lactation. Finally, there was no difference in milk production between the 2 groups of cows. These results are consistent with previous observations that showed that delaying estrous cycles after calving had no effect on milk yield and they extend those observations to late lactation. Based on milk production data, the estrogen profiles associated with recurring estrous cycles apparently do not cause bovine mammary tissue to undergo gradual involution.     

Continuous lactation in dairy cows: effect on milk production and mammary nutrient supply and extraction

Reports over the past decade have indicated that normal lactational performance can be achieved in genetically superior and high-producing dairy cows, even when the dry period between 2 lactations is omitted. The hypothesis tested in this experiment was that normal lactogenesis I and metabolic function may be achievable in continuously milked high-yielding dairy cows as a result of the genetic selection for lactation performance and hence longevity of mammary epithelial cells. The milk production and mammary nutrient uptake in response to omission of the dry period for cows with an expected peak milk yield higher than 45 kg/d were studied in 28 Holstein dairy cows managed without bovine somatotropin. Performance and metabolic parameters were followed in late gestation and in the following early lactation. Fourteen cows were milked continuously throughout late gestation, and another 14 dairy cows experienced a 7-wk prepartum dry period. Continuous milking during the prepartum period reduced milk production in the following early lactation period by >20%. The reduced milk production could not be readily ascribed to inefficiency of the mechanisms responsible for nutrient uptake by the lactating mammary epithelial cells, nor to systemic endocrine changes. This suggests that lowered mammary nutrient uptake must have been associated with reduced mammary blood flow, metabolic activity, or both, most likely as a result of disturbed lactogenesis I prepartum or lactogenesis II postpartum triggered by as yet unknown local mechanisms. Milk protein content was elevated by 0.4 percentage units in the continuously milked cows. The underlying reason is unknown, but given the current pricing system for milk, it deserves to be further investigated.     

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.     

Genetic manipulation of the IGF-I axis to regulate mammary gland development and function

Insulin-like growth factor I (IGF-I) is known to regulate mammary gland development. This regulation occurs through effects on both cell cycle progression and apoptosis. Our laboratory has studied the IGF-I-dependent regulation of these processes by using transgenic and knockout mouse models that exhibit alterations in the IGF-I axis. Our studies of transgenic mice that overexpress IGF-I during pregnancy and lactation have demonstrated that this growth factor slows the apoptotic loss of mammary epithelial cells during the declining phase of lactation but has minimal effects during early lactation on milk composition or lactational capacity. In contrast, our analysis of early developmental processes in mammary tissue from mice carrying a targeted mutation in the IGF-I receptor gene suggests that IGF-dependent stimulation of cell cycle progression is more important to early mammary gland development than potential anti-apoptotic effects. With both models, the effects of perturbing the IGF-I axis are dependent on the physiological state of the animal. The diminished ductal development that occurs in response to loss of the IGF-I receptor is dramatically restored during pregnancy, whereas the ability of overexpressed IGF-I to protect mammary cells from apoptosis does not occur if the mammary gland is induced to undergo forced involution. Data from our laboratory on the expression of IGF-signaling molecules in the mammary gland suggest that this effect of physiological context may be related to the expression of members of the insulin receptor substrate family.     

奶牛不同发育时期乳腺细胞凋亡规律的研究

为系统地研究奶牛乳腺不同发育时期细胞凋亡的规律,应用TUNEL法对奶牛不同发育时期正常乳腺组织(冰冻切片)的乳腺细胞凋亡进行了系统检测。结果表明,青春期乳腺发育缓慢,结构变化较小,乳腺细胞凋亡量相对较少;妊娠期乳腺导管持续发育,凋亡量上升,其中妊娠初期2月,乳腺腺泡大量出现,脂肪细胞凋亡随之增加,出现了一个高峰;泌乳期乳腺的结构和功能最为完善,乳腺结构变化很小,细胞凋亡量维持在很低水平;退化期腺泡瓦解,大量细胞发生凋亡,其中退化初期乳腺细胞凋亡持续增加,退化3 d达到最大值,之后凋亡量逐渐降低,退化30 d后乳腺已经基本恢复到青春期状态,凋亡细胞量也随之减少。