Natural and abrupt involution of the mammary gland affects differently the metabolic and health consequences of weaning

In most mammals under natural conditions weaning is gradual. Weaning occurs after the mammary gland naturally produces much less milk than it did at peak and established lactation. Involution occurs following the cessation of milk evacuation from the mammary glands. The abrupt termination of the evacuation of milk from the mammary gland at peak and established lactation induces abrupt involution. Evidence on mice has shown that during abrupt involution, mammary gland utilizes some of the same tissue remodeling programs that are activated during wound healing. These results led to the proposition of the “involution hypothesis”. According to the involution hypothesis, involution is associated with increased risk for developing breast cancer. However, the involution hypothesis is challenged by the metabolic and immunological events that characterize the involution process that follows gradual weaning. It has been shown that gradual weaning is associated with pre-adaption to the forthcoming break between dam and offspring and is followed by an orderly reprogramming of the mammary gland tissue. As discussed herein, such response may actually protect the mammary glands against the development of breast cancer and thus, may explain the protective effect of extended breastfeeding. On the other hand, the termination of breastfeeding during the first 6 months of lactation is likely associated with an abrupt involution and thus with an increased risk for developing breast cancer. Review of the literature on the epidemiology of breast cancer principally supports those conclusions.     

Sows with high milk production had both a high feed intake and high body mobilization

Selection for increased litter size have generated hyper-prolific sows that nurses large litters, however limited knowledge is available regarding the connection between milk production, feed intake and body mobilization of these modern sows. The aim of the current study was to determine what characterized sows with high milk production and nursing large litters, differences between sows of different parities and effects of lactational performance on next reproductive cycle. In total 565 sows (parity 1 to 4) were studied from 7 days before farrowing until weaning. On day 2 postpartum litters were standardized to 14 piglets. Weight and back fat thickness of sows were measured at day 7 prepartum, day 2 postpartum and at weaning. Litters were weighed at day 2 and at weaning. Pearson correlation coefficients between variables were calculated and regression models were developed. The average daily feed intake (ADFI) of the sows was 6.1±1.1 kg/day, average daily gain (ADG) of the litter was 2.92±0.53 kg/day and sows weaned 13.0±1.1 piglets. First parity sows generally had a lower ADFI and milk production and a decrease in total born piglets in next litter compared with parity 2 to 4 sows, which could be explained by a relatively higher proportion of their body reserves being mobilized compared with multiparous sows. The ADG of the litter was positively related by ADFI of the sows, litter size and BW loss and increasing the ADFI with 1 kg/day throughout lactation likely increased the ADG of the litter with 220 to 440 g/day in parity 1 to 4, respectively. Increasing the ADFI by 1 kg/day reduced the BW loss with 6.6 to 13.9 kg of parity 1 to 4 sows, respectively, during lactation, whereas increasing the average milk yield with 1 kg/day raised the BW loss with 4.3 to 21.0 kg of the four parities during lactation. The number of total born piglets in the next litter was positively related to the number of piglets born in the previous litter. In conclusion, both a high feed intake and a high mobilization of body reserves was a prerequisite for a high milk production. The sows might be very close to the physical limit of what they can ingest and future research should therefore, focus on optimizing the dietary energy and nutrient concentrations of diets for lactating hyper-prolific sows and herein distinguish between primiparous and multiparous sows.     

Effects of maternal alpha-ketoglutarate supplementation during lactation on the performance of lactating sows and suckling piglets

ABSTRACT

The aim of the study was to investigate if dietary alpha-ketoglutarate (AKG) supplementation may improve the performance of lactating sows and their suckling piglets. After farrowing, 24 lactating sows (Large White × Landrace) with similar body weight (BW) were assigned to the control and AKG groups based on parity, and their lactation diets were supplemented with 0.00 or 0.25% AKG, respectively. It was found that supplementing the diet of lactating sows with 0.25% AKG enhanced growth performance of the suckling piglets from d 7 to d 21 of the lactation period, improved villus height of ileum and tended (p = 0.085) to increase mean volumetric bone mineral density of femur in the weanling piglets. In the lactating sows, dietary supplementation of AKG decreased plasma urea level on d 14 of lactation, decreased plasma calcium (Ca) concentrations from d 7 to d 21 of lactation and increased lactose and Ca levels in ordinary milk. Thus, it was proposed that AKG supplementation stimulates the capacity for lactose synthesis and Ca uptake in the mammary gland, thereby altering the composition of the ordinary milk which might be associated with the enhanced performance of piglets during the suckling period. These findings could lead to a better application of AKG in lactating nutrition, and therefore, promoting pork production.     

Glucocorticoid and progesterone inhibit involution and programmed cell death in the mouse mammary gland

Milk production during lactation is a consequence of the suckling stimulus and the presence of glucocorticoids, prolactin, and insulin. After weaning the glucocorticoid hormone level drops, secretory mammary epithelial cells die by programmed cell death and the gland is prepared for a new pregnancy. We studied the role of steroid hormones and prolactin on the mammary gland structure, milk protein synthesis, and on programmed cell death. Slow-release plastic pellets containing individual hormones were implanted into a single mammary gland at lactation. At the same time the pups were removed and the consequences of the release of hormones were investigated histologically and biochemically. We found a local inhibition of involution in the vicinity of deoxycorticosterone- and progesterone-release pellets while prolactin-release pellets were ineffective. Dexamethasone, a very stable and potent glucocorticoid hormone analogue, inhibited involution and programmed cell death in all the mammary glands. It led to an accumulation of milk in the glands and was accompanied by an induction of protein kinase A, AP-1 DNA binding activity and elevated c-fos, junB, and junD mRNA levels. Several potential target genes of AP-1 such as stromelysin-1, c-jun, and SGP-2 that are induced during normal involution were strongly inhibited in dexamethasone-treated animals. Our results suggest that the cross-talk between steroid hormone receptors and AP-1 previously described in cells in culture leads to an impairment of AP-1 activity and to an inhibition of involution in the mammary gland implying that programmed cell death in the postlactational mammary gland depends on functional AP-1.     

乳腺重构的过程及其调节因素

受到妊娠周期的影响，乳腺组织在雌性哺乳动物一生中经历着妊娠-哺乳-退化的周期性发育变化. 在乳腺退化到再次泌乳的过程中，乳腺细胞经历凋亡和更新，从而实现乳腺组织的自我更新和修复，即乳腺重构. 重构期间乳腺在组织结构和生理过程中发生显著变化，但该过程物种间差异较大. 乳用家畜为维持泌乳，妊娠期和干奶期重叠，展示出独特的再生性乳腺重构. 再生性乳腺重构对乳畜乳腺健康和下一周期的泌乳具有重要意义，研究此过程将为后续调控乳腺自我更新和改善乳腺健康提供思路. 本综述总结了近年来动物乳腺重构的研究进展，系统归纳了影响乳腺重构的因素，包括激素、蛋白酶、细胞因子、热应激、氧化应激、光照周期等，旨在解析乳腺重构的生理机制，为精准调控该过程提供科学依据.     

Leukemia inhibitory factor induces apoptosis of the mammary epithelial cells and participates in mouse mammary gland involution

Leukemia inhibitory factor (LIF) is a multifunctional glycoprotein that displays multiple biological activities in different cell types, but to date there has been no report on its expression in the normal mammary gland. In this study we found that LIF is expressed at low but detectable levels in postpubertal, adult virgin, and pregnant mouse mammary glands. However, LIF expression drops after parturition to become almost undetectable in lactating glands. Interestingly, LIF expression shows a steep increase shortly after weaning that is maintained for the following 3 days. During this period, known as the first stage of mammary gland involution, the lack of suckling induces local factors that cause extensive epithelial cell death. It has been shown that Stat3 is the main factor in signaling the initiation of apoptosis, but the mechanism of its activation remains unclear. Herein, we show that LIF expression in the gland is induced by milk stasis and not by the decrease of circulating lactogenic hormones after weaning. Implantation of LIF containing pellets in lactating glands results in a significant increase in epithelium apoptosis. In addition, this treatment also induces Stat3 phosphorylation. We conclude that LIF regulated expression in the mouse mammary gland may play a relevant role during the first stage of mammary gland involution. Our results also show that LIF-induced mammary epithelium apoptosis could be mediated, at least partially, by Stat3 activation.     

Ovulation frequency among sows group-housed during late lactation

Ovulation frequency during late lactation was determined among 114 sows from four commercial farms that group-housed the sows from about 3 weeks of lactation until weaning (G-farms), and among 21 sows from one farm that kept the sows individually penned throughout lactation (C-farm). Ovulation frequency was determined by applying a progesterone assay on faecal samples collected at weekly intervals from time of grouping until 3 weeks after weaning. The groups consisted of 11–22 sows and boar contact was not allowed during the 5–6 week lactation period. G-farm sows were fed ad libitum while C-farm sows were provided with a restricted food ration. During the group-housing period, 28% of the G-farm sows ovulated, whereas none of the singly housed sows ovulated during the corresponding period (P = 0.005). Ovulation frequency varied considerably between sow groups (0–54%) (P = 0.004), owing partly to differences in age. Not a single primiparous sow ovulated, whereas ovulation frequency among second to fourth parity sows and older sows (fifth parity and over) was 6% and 48%, respectively (P < 0.001). At the time of grouping and weaning, neither backfat thickness nor litter size differed between the sows that ovulated and those that were anoestrous. Preweaning mammary gland atrophy, indicating that milk production had ceased, was noted in 16% of the G-farm sows that ovulated but in only one (1%) of the anoestrus sows. Only 65% of the sows showing lactational ovulation were mated within 10 days after weaning. By contrast, 87% of the G-farms sows that were anoestrus during lactation and 100% of the C-farm sows were mated within this period.     

Effect of oral polyamine supplementation pre-weaning on piglet growth and intestinal characteristics

A high proportion of piglets fail to adapt to the changing composition of their diet at weaning, resulting in weight loss and increased susceptibility to pathogens. Polyamines are present in sow milk and promote neonatal maturation of the gut. We hypothesised that oral spermine and spermidine supplementation before weaning would increase piglet growth and promote gastrointestinal development at weaning. In Experiment One, one pair of liveweight (LW)-matched piglets per litter from first and third lactation sows received 2 ml of a 0 (Control) or 463 nmol/ml spermine solution at 14, 16, 18, 20 and 22 days of age (n=6 piglets/treatment per parity). Villus height and crypt depth in the duodenum and jejunum were measured at weaning (day 23 postpartum). In Experiment Two, piglets suckling 18 first and 18 third lactation sows were used. Within each litter, piglets received 2 ml of either water (Control), 463 nmol/ml spermine solution or 2013 nmol/ml spermidine solution at 14, 16, 18, 22 and 24 days of age (n=54 piglets/treatment per sow parity). Piglets were weighed individually at 14, 18, 24 (weaning) and 61 days of age. In Experiment One, oral spermine supplementation resulted in a 41% increase in villus height, a 21% decrease in crypt depth and 79% decrease in the villus height : crypt depth ratio compared with control piglets (P<0.01). In Experiment Two, spermine and spermidine-supplemented piglets suckling first lactation sows grew faster (P<0.05) between days 14 and 18 postpartum than control piglets: 0.230±0.011 and 0.227±0.012 v. 0.183±0.012 kg/day, respectively. Spermine supplementation tended (P<0.1) to increase piglet LW gain from weaning to day 37 post-weaning compared with control piglets (0.373±0.009 v. 0.341±0.010 kg/day). In conclusion, spermine supplementation increased villus height at weaning, and appears to have the potential to improve the pre- and post-weaning growth of conventionally weaned piglets.     

Regulatory role for amino acids in mammary gland growth and milk synthesis

The health and growth of mammalian neonates critically depend on the yield and composition of their mothers' milk. However, impaired lactogenesis occurs in both women in response to stress and hormonal imbalance and in primiparous sows which exhibit low voluntary feed intake and underdevelopment of mammary tissues. Because of ethical concerns over lactation research with women and children, swine is often used as an animal model to study mammary gland development and the underlying regulatory mechanisms. Available evidence from work with lactating sows shows that amino acids are not only building blocks for protein but are also key regulators of metabolic pathways critical to milk production. Particularly, arginine is the common substrate for the generation of nitric oxide (NO; a major vasodilator and angiogenic factor) and polyamines (key regulators of protein synthesis). Thus, modulation of the arginine-NO pathway may provide a new strategy to enhance the growth (including vascular growth) of mammary tissue and its uptake of nutrients, therefore improving lactation performance in mammals. In support of this proposition, supplementing 0.83% L: -arginine (as 1% L: -arginine-HCl) or 50 mg/day diethylenetriamine-NO adduct (NO donor) to diets of lactating primiparous sows increased milk production and the growth of suckling piglets. Future studies with animal models (e.g., pigs, sheep, cows, and rats) are necessary to elucidate the underlying mechanisms at molecular, cellular, tissue, and whole-body levels.     

Effects of reduced suckling on days to estrus, conception during lactation and embryo survival in sows

Trials to investigate the effects of limited suckling on sow reproduction and piglet growth were conducted using 41 first parity and 32 second parity Yorkshire sows. Separation of sows from their litters (22 hrs/day, days 21-35 postpartum) induced estrus in 60% of primiparous and 72% of second parity sows during lactation. Compared to control group animals, primiparous sows had higher weaning weights and second parity sows higher rates of embryo survival on day 30 of gestation. Piglets subjected to suckling restriction had weights, at 2 weeks after weaning, equal to those weaned after 5 weeks of unrestricted suckling. We conclude that suckling restriction can provide the dual benefits of an extended piglet nursing period and a decreased breeding to breeding interval in sows.     

Transforming growth factor beta3 induces cell death during the first stage of mammary gland involution

Involution of the mammary gland following weaning is divided into two distinct phases. Initially, milk stasis results in the induction of local factors that cause apoptosis in the alveolar epithelium. Secondly after a prolonged absence of suckling, the consequent decline in circulating lactogenic hormone concentrations initiates remodeling of the mammary gland to the virgin-like state. We have shown that immediately following weaning TGFbeta3 mRNA and protein is rapidly induced in the mammary epithelium and that this precedes the onset of apoptosis. Unilateral inhibition of suckling and hormonal reconstitution experiments showed that TGFbeta3 induction is regulated by milk stasis and not by the circulating hormonal concentration. Directed expression of TGFbeta3 in the alveolar epithelium of lactating mice using a beta-lactoglobulin promoter mobilized SMAD4 translocation to the nucleus and caused apoptosis of these cells, but not tissue remodeling. Transplantation of neonatal mammary tissue derived from TGFbeta3 null mutant mice into syngenic hosts resulted in a significant inhibition of cell death compared to wild-type mice upon milk stasis. These results provide direct evidence that TGFbeta3 is a local mammary factor induced by milk stasis that causes apoptosis in the mammary gland epithelium during involution.     

Fighting During Suckling: Is it Really an Epiphenomenon?

Suckling by piglets and kittens is accompanied by intense fighting among littermates. There are strong arguments that support the fighting for teats as an epiphenomenon, such as there being a sufficient number of mammary glands (teats) that are of equal quality for littermates, as suggested by Hudson and Distel (Ethology, 119, 2013, 353). However, this article presents a possible adaptive explanation for fighting during suckling. To substantiate the adaptive function of suckling fights, the disposability and limitations of colostrum are first considered. Other aspects are also discussed, such as the potential role of social thermoregulation, the stimulation of mammary glands (massage) and milk composition. Adaptive explanations for the absence/presence and intensity of suckling fights across species consider differences in the colostrum and mature milk composition, mechanisms of transferring immunoglobulin that supply passive immunity to neonates, strategies used to compete for teats and litter size. However, agonistic behaviours in the context of suckling should not be simply categorised as an epiphenomenon.     

Macrophages are crucial for epithelial cell death and adipocyte repopulation during mammary gland involution

Mammary gland development is dependent on macrophages, as demonstrated by their requirement during the expansion phases of puberty and pregnancy. Equally dramatic tissue restructuring occurs following lactation, when the gland regresses to a state that histologically resembles pre-pregnancy through massive programmed epithelial cell death and stromal repopulation. Postpartum involution is characterized by wound healing-like events, including an influx of macrophages with M2 characteristics. Macrophage levels peak after the initial wave of epithelial cell death, suggesting that initiation and execution of cell death are macrophage independent. To address the role of macrophages during weaning-induced mammary gland involution, conditional systemic deletion of macrophages expressing colony stimulating factor 1 receptor (CSF1R) was initiated just prior to weaning in the Mafia mouse model. Depletion of CSF1R(+) macrophages resulted in delayed mammary involution as evidenced by loss of lysosomal-mediated and apoptotic epithelial cell death, lack of alveolar regression and absence of adipocyte repopulation 7 days post-weaning. Failure to execute involution occurred in the presence of milk stasis and STAT3 activation, indicating that neither is sufficient to initiate involution in the absence of CSF1R(+) macrophages. Injection of wild-type bone marrow-derived macrophages (BMDMs) or M2-differentiated macrophages into macrophage-depleted mammary glands was sufficient to rescue involution, including apoptosis, alveolar regression and adipocyte repopulation. BMDMs exposed to the postpartum mammary involution environment upregulated the M2 markers arginase 1 and mannose receptor. These data demonstrate the necessity of macrophages, and implicate M2-polarized macrophages, for epithelial cell death during normal postpartum mammary gland involution.     

Distinct behavior of claudin-3 and -4 around lactation period in mammary alveolus in mice

Tight junctions (TJs) are the most apical junctional complexes and restrict the fluid flux through the paracellular pathway. In the mammary glands, the tightness of TJs occurs shortly after parturition to prevent the leakage of milk components from the lumen and the loosening of TJs is induced immediately after weaning. Claudins are transmembrane proteins, and their composition at the apical-most regions determines the permeability of TJs. In this study, we investigated the localization and expression patterns of claudin-3 and -4 in the mammary glands around the lactation period because it is unclear how claudins construct mammary TJs in the apical-most regions. Our results showed that claudin-3 and -4 change not only their level of expression but also their localization in the processes of parturition, lactation, and weaning. Claudin-3 was concentrated in the apical-most regions during lactation, whereas claudin-4 gradually decreased at the beginning of lactation and increased drastically immediately after weaning. The qualitative change of claudin-3 was also identified by western blotting analysis as an additional band around the lactation period. In addition, parts of the mammary epithelial cells showed intensive positive reactions to claudin-4 in the lateral membrane and cytoplasm after weaning, concurrently with the involution mammary glands. These results indicate that claudin-3 in the apical-most regions maintains the impermeable TJs during lactation, and claudin-4 contributes to the permeability changes of TJs immediately after parturition and weaning.     

Effect of crate opening from day 3 postpartum to weaning on nursing and suckling behaviour in domestic pigs

Temporary crating may be a more acceptable housing system for lactating sows than permanent crating and loose-housing because it combines benefits of both systems while reducing some of their limitations. It remains unclear whether nursing and sucking behaviour is influenced after crate opening. The aim of this study was to assess the short- (24 h post-crate opening) and long-term (day 25 postpartum (pp.)) effects of opening the farrowing crate from day 3 pp. to weaning on nursing and suckling behaviour. Sows were crated from 5 days prepartum either to weaning (permanently crated group; n = 14) or 3 days pp. (temporarily crated group; n = 13). Sows and their litters were observed on days 4 and 25. Duration of pre- and post-massages, nursing termination, number of piglets missing milk ejection and number of piglets fighting during pre- and post-massages were scored at 15-s intervals. Nursing success (i.e. with or without milk ejection) was also recorded. Data were analysed using PROC GLM and PROC GENMOD of SAS including housing, litter size and parity as fixed effects. Nursing behaviour did not differ between sows housed in temporary crates and those housed in permanent crates on days 4 and 25 pp., that is, same number of nutritive nursings (NNs), same proportion of non-NNs, same duration of post-massages and same proportion of termination of post-massages. There was only a housing effect on day 25; with sows having longer pre-massages in permanent crates (P < 0.05). Suckling behaviour was overall similar between treatments. There were no differences in the number of piglets attending pre- and post-massages, proportion of piglets fighting during pre-and post-massages and the proportion of piglets missing milk ejection on both days. The only housing effect was found on day 25 during which fewer piglets attended post-massages (P < 0.05) in permanent crates. Sows with larger litters terminated post-massages more often (P < 0.05), allowed shorter post-massages (P < 0.05) on day 4, and had more piglets miss milk ejection on days 4 and 25 (P < 0.05). In conclusion, the results of this study showed that housing had a very limited effect on nursing and suckling behaviour. Sow and piglet behaviours were not altered after crate opening (short-term effect) and nursing was to some extent calmer (shorter pre-massages and more piglets attended post-massages) in temporary crates on day 25. Increased litter size impaired nursing and suckling behaviour of sows and piglets independently of the housing system.     

Differential expression of TGF-β isoforms during postlactational mammary gland involution

After cessation of lactation, the mammary gland undergoes involution, which is characterized by a massive epithelial cell death and proteolytic degradation of the extracellular matrix. Whereas the expression patterns and also the function of TGF-beta isoforms during mammary gland branching morphogenesis and lactation are well understood, their expression during postlactational involution and therefore a possible role in this process is poorly known. In this study we show that TGF-beta3 expression is dramatically induced (>fivefold) during mouse mammary gland involution when compared to that of virgin mouse, reaching a maximal expression level at day 4 after weaning. In contrast, other TGF-beta isoforms do not display significant increase in expression during involution (TGF-beta1, 1.3-fold and TGF-beta2, <1.5-fold) when compared to that of virgin or lactating mice. During mammary gland involution, TGF-beta3 is expressed in the epithelial layer and particularly in myoepithelial cells. A comparison of the kinetics of TGF-beta3 expression to that of programmed cell death and degradation of the basement membrane suggests that TGF-beta3 functions in the remodeling events of the extracellular matrix during the second stage of involution.     

Body weight loss during lactation and its influence on weaning-to-service interval and ovulation rate in Landrace and Yorkshire sows in the tropical environment of Thailand

The aim of this study was to investigate the ovulation rate and the weaning-to-service interval (WSI) of sows in relation to their body weight loss during lactation in tropical climatic conditions. Effect of lactation length (LL), number of total born piglets, number of live born piglets, litter birth weight, average piglet birth weight, number of pigs weaned, litter weaning weight and average pig weaned weight on sow weight loss during lactation were also studied. This study was conducted in two commercial purebred sow herds (A, B) in the central part of Thailand from August to December 1997. The herds had both Landrace (L) and Yorkshire (Y) sows. The 123 sows (55 L and 68 Y) in herd A and 153 sows (95 L and 58 Y) in herd B, parity 1-4, were weighed within 4 days after farrowing and at weaning. Lactation length, litter size at birth and at weaning, litter weight at birth and at weaning, and WSI were recorded for each of these sows. In herd A, 52 sows (20 L and 32 Y) were examined once by laparoscopy between days 8 and 14 after AI-service. These sows had farrowed at least seven piglets in the previous parturition. The numbers of corpora lutea (CL) in both ovaries were counted, and were assumed to equal the ovulation rate. L-sows had significantly (P < 0.05) higher relative weight loss during lactation (RWL) than Y-sows. The RWL increased by 0.7% for each extra pig weaned. When LL increased by 1 day, within the interval of 17-34 days, RWL decreased by 0.6%. Sows with a high weight loss had significantly (P < 0.05) longer WSI than sows with medium or low weight loss. Weight loss had a significant (P < 0.05) effect on WSI in parity 1 and 2 sows. Y-sows had more CL than L-sows (15.7 versus 14.0) (P < 0.05). RWL, parity and regression on lactation length had no significant effect on number of CL. In conclusion, sows with higher number of pigs weaned lose more weight. Under the restricted feeding regime applied, high weight loss during lactation prolongs WSI in parity 1 and 2 sows, but has no influence on the ovulation rate at first oestrus after weaning. The ovulation rate is higher in Yorkshire than in Landrace sows. The ovulation rate is independent of parity.     

Expression of Lysostaphin in Milk of Transgenic Mice Affects the Growth of Neonates

As an initial step towards enhancing mastitis resistance in dairy animals, we generated BLG-Lys transgenic mice that secrete lysostaphin, a potent antistaphylococcal protein, in their milk. In the current study, we continue our assessment of lysostaphin as a suitable antimicrobial protein for mastitis resistance and have investigated mammary gland development and function in three lines of transgenic mice. As the lines were propagated, there was a tendency for fewer BLG-Lys litters to survive to weaning (51% as compared to 90% for nontransgenic lines, p = 0.080). Nontransgenic pups fostered on dams from these three lines exhibited diminished growth rates during the first week of lactation. Rates of gain became comparable to pups on nontransgenic dams at later time points. Initial slow growth also resulted in decreased weaning weights for pups nursed by transgenic dams (15.35±0.27 g) when compared to pups delivered and nursed by nontransgenic dams (18.61 ± 0.61 g; p < 0.001), but the effect was temporary, as similar weights were attained by adulthood. Milk yield at peak lactation was not different between BLG-Lys (0.79 ± 0.33 g) and nontransgenic (0.91 ± 0.38 g; p = 0.166) dams. Histological examination of the transgenic mammary glands during gestation revealed no differences when compared to control glands; however, at early lactational stages, the BLG-Lys glands exhibited less alveolar area than control glands and a delay in lobulo-alveolar maturation. The results clearly demonstrate reduced growth of neonates on BLG-Lys dams; whether the poor pup performance can be attributed to delayed mammary development or the gland development merely reflects reduced suckling stimuli from the pups remains to be determined.Authors Abhijit Mitra and Kathleen S. Hruska contributed equally to this work     

Milk-protein mRNAs and poly(A) in the involuting rat mammary gland return to the levels found during late pregnancy

Analyses of the rat mammary gland show that the increase in the milk-protein mRNAs during the development of lactation and the rapid disappearance of these sequences during involution are not accompanied by similar changes in the poly(A) content. During the development of lactation the casein mRNA is initially in great excess to the whey-protein mRNA and this differential expression of the genes for the two types of milk proteins is again observed during early involution. Since the amounts of poly(A) and of both milk-protein mRNAs are also similar to the amounts found in the gland during late pregnancy, these results indicate that during early involution the mammary gland has reverted to the pattern of mRNA metabolism that occurs during late pregnancy.