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Milk fat is the foremost nutrient of milk and a vital indicator in evaluating milk quality. Accumulating evidence suggests that microRNAs (miRNAs) are involved in the synthesis of milk fat. The miR-200c is closely related to lipid metabolism, but little is known about its effect on the synthesis of milk fat in MECs of ewes. Herein, the effect of miR-200c on the proliferation of ovine mammary epithelial cells (MECs) and its target relationship with a predicted target gene were investigated. The regulatory effects of miR-200c on the expression of the target genes and the content of triglycerides in ovine MECs were further analyzed. The results revealed that the expression level of miR-200c was differentially expressed in both eight tissues selected during lactation and in mammary gland tissues at different physiological periods. Overexpression of miR-200c inhibited the viability and proliferation of ovine MECs, while inhibition of miR-200c increased cell viability and promoted the proliferation of ovine MECs. Target gene prediction results indicated that miR-200c would bind the 3′UTR region of pantothenate kinase 3 (PANK3). Overexpression of miR-200c reduced the luciferase activity of PANK3, while inhibition of miR-200c increased its luciferase activity. These findings illustrated that miR-200c could directly interact with the target site of the PANK3. It was further found that overexpression of miR-200c reduced the expression levels of PANK3 and, thus, accelerated the synthesis of triglycerides. In contrary, the inhibitor of miR-200c promoted the expression of PANK3 that, thus, inhibited the synthesis of triglycerides in ovine MECs. Together, these findings revealed that miR-200c promotes the triglycerides synthesis in ovine MECs via increasing the lipid synthesis related genes expression by targeting PANK3. [ABSTRACT FROM AUTHOR]

Heat stress is a major threat to cattle reproduction today. It has been shown that the effect of high temperature not only has a negative effect on the hormonal balance, but also directly affects the quality of oocytes, disrupting the function of mitochondria, fragmenting their DNA and changing their maternal transcription. Studies suggest that the induction of HSP70 may reduce the apoptosis of granular layer cells caused by heat stress. It has been shown that the changes at the transcriptome level caused by heat stress are consistent with 46.4% of blastocyst development disorders. Cows from calves exposed to thermal stress in utero have a lower milk yield in their lifetime, exhibit immunological disorders, have a lower birth weight and display a shorter lifespan related to the expedited aging. In order to protect cow reproduction, the effects of heat stress at the intracellular and molecular levels should be tracked step by step, and the impacts of the dysregulation of thermal homeostasis (i.e., hyperthermy) should be taken into account. [ABSTRACT FROM AUTHOR]

The effects of dietary supplementation with citrus peel extract (CPE) on milk biochemical parameters, milk bacterial community, and milk metabolites were evaluated. Eight lactating cows were allocated to a replicated 4 × 4 Latin square. Experimental treatments included the control diet (CON), and CON supplemented with CPE at 50 g/d (CPE50), 100 g/d (CPE100), and 150 g/d (CPE150). Supplementing with CPE linearly decreased milk interleukin-6 and malondialdehyde concentrations and linearly increased lysozyme activity and 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity. Compared with CON, the milk of CPE150 cows had fewer abundances of several opportunistic pathogens and psychrotrophic bacteria, such as Escherichia-Shigella, Sphingobacterium, Alcaligenes, Stenotrophomonas, and Ochrobactrum. Supplementing with CPE significantly altered the metabolic profiling in the milk. The metabolites of flavonoids were enriched in the milk of cows fed CPE150, while some proinflammation compounds were decreased compared with CON. Correlation analysis showed that the change in the bacterial community might partly contribute to the alteration in the expression of milk cytokines. In conclusion, CPE exerts health-promoting effects (e.g., antioxidant, anti-microbial, and anti-inflammatory) in the mammary metabolism of cows due to its flavonoid compounds, which also provide additional value in terms of milk quality improvement. [ABSTRACT FROM AUTHOR]

Mastitis is an inflammation of the mammary gland initiated by pathogenic bacteria. In fact, mastitis is the second most important reason for the culling of cows from dairy herds, after infertility. In this review we focus on various forms of mastitis, including subclinical and clinical mastitis. We also stress the importance of the dry-off period as an important time when pathogenic bacteria might start their insult to the mammary gland. An important part of the review is the negative effects of mastitis on milk production and composition, as well as economic consequences for dairy farms. The two most important groups of bacteria that are involved in infection of the udder, Gram-negative and Gram-positive bacteria, are also discussed. Although all cows have both innate and adaptive immunity against most pathogens, some are more susceptible to the disease than others. That is why we summarize the most important components of innate and adaptive immunity so that the reader understands the specific immune responses of the udder to pathogenic bacteria. One of the most important sections of this review is interrelationship of mastitis with other diseases, especially retained placenta, metritis and endometritis, ketosis, and laminitis. Is mastitis the cause or the consequence of this disease? Finally, the review concludes with treatment and preventive approaches to mastitis. [ABSTRACT FROM AUTHOR]

Maternal care is essential to optimally support survival of the offspring. During evolution of mammalian species, different phenotypes have evolved in relation to gestation length, number, size, and maturation stage of the offspring at parturition, as well as colostrum and milk composition. The aim of the present review is to describe relationships between placental function and colostrum and milk composition in different mammalian species. Species covered in this article include humans, rabbits, rodents (rat and mouse), carnivores (cats and dogs), and a variety of ungulate species (cattle, sheep, goats, pigs, and horses). Species-specific aspects are elucidated with a special focus on the transfer of passive immunity. In this regard, the structure and thus the capability of the placenta to transport immunoglobulins from maternal to fetal circulation in utero dictates the necessity of the passive transfer of immunity via colostrum. Consequently, species with exclusive postpartal transfer of immunity such as in all ungulate species have greater immunoglobulin G concentrations in colostrum than species with a prepartal transfer in utero, where especially immunoglobulin A with its local immune function in the gastrointestinal tract is present in colostrum (e.g. rabbit and human). In terms of the nutritional purpose, suckling frequency is an important factor determining the gross composition of colostrum as well as in the mature milk of these species. Milk of nidicolous animals with long intervals in-between suckling events contains more fat than milk of nidifugous animals with constant access to their mother. However, the importance of colostrum and milk consumption for newborn animals and human babies goes beyond nutrition and the transfer of immunity. Numerous bioactive components such as growth factors, hormones, and oligosaccharides are enriched in colostrum and transition milk, which support the development of the intestinal tract and local immune system. [ABSTRACT FROM AUTHOR]

Fascin expression has commonly been observed in certain subtypes of breast cancer, where its expression is associated with poor clinical outcome. However, its role in normal mammary gland development has not been elucidated. Here, we used a fascin knockout mouse model to assess its role in normal mammary gland morphogenesis and lactation. Fascin knockout was not embryonically lethal, and its effect on the litter size or condition at birth was minimal. However, litter survival until the weaning stage significantly depended on fascin expression solely in the nursing dams. Accordingly, pups that nursed from fascin−/− dams had smaller milk spots in their abdomen, suggesting a lactation defect in the nursing dams. Mammary gland whole-mounts of pregnant and lactating fascin−/− mice showed significantly reduced side branching and alveologenesis. Despite a typical composition of basal, luminal, and stromal subsets of mammary cells and normal ductal architecture of myoepithelial and luminal layers, the percentage of alveolar progenitors (ALDH+) in fascin−/− epithelial fraction was significantly reduced. Further in-depth analyses of fascin−/− mammary glands showed a significant reduction in the expression of Elf5 , the master regulator of alveologenesis, and a decrease in the activity of its downstream target p-STAT5. In agreement, there was a significant reduction in the expression of the milk proteins, whey acidic protein (WAP), and β-casein in fascin−/− mammary glands. Collectively, our data demonstrate, for the first time, the physiological role of fascin in normal mammary gland lactogenesis, an addition that could reveal its contribution to breast cancer initiation and progression. [Display omitted] [ABSTRACT FROM AUTHOR]

Mammary tumors are the most common diseases of canine mammary gland and most frequent neoplasms both benign and malignant, in female dogs. However, mammary gland enlargement and changes may be related to a wide variety of other pathologies. Thus the differential diagnosis should be performed carefully in order to institute an adequate treatment. In this article chosen nonneoplastic disorders like mastitis, hyperplastic and dysplastic changes in canine mammary gland were described. [ABSTRACT FROM AUTHOR]

To understand how genes precisely regulate lactation physiological activity and the molecular genetic mechanisms underlying mammary gland involution, this study investigated the transcriptome characteristics of goat mammary gland tissues at the late gestation (LG), early lactation (EL), peak lactation (PL), late lactation (LL), dry period (DP), and involution (IN) stages. A total of 13,083 differentially expressed transcripts were identified by mutual comparison of mammary gland tissues at six developmental stages. Genes related to cell growth, apoptosis, immunity, nutrient transport, synthesis, and metabolism make adaptive transcriptional changes to meet the needs of mammary lactation. Notably, platelet derived growth factor receptor beta (PDGFRB) was screened as a hub gene of the mammary gland developmental network, which is highly expressed during the DP and IN. Overexpression of PDGFRB in vitro could slow down the G1/S phase arrest of goat mammary epithelial cell cycle and promote cell proliferation by regulating the PI3K/Akt signaling pathway. In addition, PDGFRB overexpression can also affect the expression of genes related to apoptosis, matrix metalloproteinase family, and vascular development, which is beneficial to the remodeling of mammary gland tissue during involution. These findings provide new insights into the molecular mechanisms involved in lactation and mammary gland involution. [ABSTRACT FROM AUTHOR]

The objective of this study was to test the hypothesis that stearic acid (SA) supplementation increases milk fat content and overcomes the antilipogenic effects of trans-10, cis-12 conjugated linoleic acid (CLA) in lactating ewes. Twenty-eight Lacaune ewes (36 (sd 2) days in lactation; 70·5 (sd) 9·6 kg of body weight), producing 1·8 (sd 0·4) kg of milk/d, were used in a completely randomised design (seven ewes/treatment) for 21 d. The treatments were: (1) Control; (2) CLA (6·4 g/d of trans-10, cis-12 CLA); (3) SA (28 g/d of SA) and (4) SA in association with trans-10, cis-12 CLA (CLASA; 6·4 g/d of trans-10, cis-12 CLA plus 28 g/d of SA). All data were analysed using a mixed model that included the fixed effect of treatment and the random effect of ewe. SA did not alter milk fat content and yield relative to Control (91·9 v. 91·2 (sd 4·1) g/d). CLASA was not able to overcome the reduction in fat content and fat yield induced by CLA (75 v. 82 (sd 0·14) g/d). SA increased the relative abundance of CD36, fatty acid-binding protein 4 (FABP4) and PPAR-γ mRNA by 140, 112 and 68 % compared with CLASA. SA also reduced the relative abundance of acetyl-CoA carboxylase α promoter II and stearoyl-CoA desaturase (SCD) when compared with Control (45 and 39 %). Compared with CLA, CLASA treatment had no effect on the mRNA abundance of fatty acid synthase, lipoprotein lipase, CD36, SCD, FABP4, acylglycerolphosphate acyltransferase 6, sterol regulatory element-binding protein 1 and PPAR-γ. In conclusion, SA supplementation did not increase milk fat synthesis and did not overcome the CLA-induced milk fat depression when associated with trans-10, cis-12 CLA. [ABSTRACT FROM AUTHOR]

Heat stress (HS) leads to substantial economic loss of dairy industry each year. The negative effect of HS in dairy cows is becoming one of the more urgent issue due to accelerating side-effects of global warming. Various genes are involved in HS response but the information about the role of noncoding RNAs, especially circular RNAs (circRNAs) is largely unknown. In our study, we aimed to investigate the different expression profile of circRNAs between HS and Non-heat-stressed condition (NC) of Chinese Holstein cow's mammary gland. CircRNAs were identified using RNA sequencing and bioinformatics analysis. In total, 37405 circRNAs were detected and 95 were differentially expressed (DE), including 15 downregulated and 80 upregulated circRNAs in HS group compared to NC. Eight circRNAs were randomly selected to verify the RNA sequencing result. Further, Sanger sequencing validated the backsplicing site of the eight circRNAs. Moreover, results obtained from the Quantitative real time PCR (qRT-PCR) showed consistent expression trend with that of RNA sequencing. GO annotation and KEGG analysis suggested that these DE circRNAs probably involved in the energy metabolic regulation. Furthermore, we constructed ceRNA network and the result indicated that these DE circRNAs could regulate lactation through IGF1 and PRL signaling pathway. [ABSTRACT FROM AUTHOR]

Calliandra portoricensis (C. portoricensis) is used in herbal homes in Nigeria to manage breast diseases. We investigated the anti-tumourigenic effects of chloroform extract of C. portoricensis (CP) in breast experimental cancer induced by N-methyl-N-nitrosourea (NMU) and benzo-(a)-pyrene (BaP). Fifty-six female rats were assigned into seven equal groups: Group 1 served as control, group 2 received NMU and BaP (50 mg/kg, each), groups 3 and 4 received [NMU + BaP] and treated with CP at 50 and 100 mg/kg, respectively. Group 5 received CP (100 mg/kg), group 6 received [NMU + BaP] and vincristine (0.5 mg/kg), while group 7 received vincristine (0.5 mg/kg). The NMU and BaP (i.p) were dissolved in normal saline and corn oil, respectively. The CP (oral) and vincristine (i.p) were given thrice and twice per week, respectively for 10 weeks. The [NMU + BaP] intoxication significantly decreased body weight gain by 32% while organo-somatic weight of mammary gland increased by 37%. Also, [NMU + BaP] decreased the activities of mammary catalase, glutathione-s-transferase, glutathione peroxidase, superoxide dismutase and total sulphurhydryl by 34%, 31%, 35%, 35% and 33%, respectively. The [NMU + BaP] increased inflammatory and oxidative stress markers; nitrite, lipid peroxidation and myeloperoxidase by 62%, 57% and 361%, respectively. Strong expression of BCL-2, IL-6, COX 2, β-catenin and iNOS in [NMU + BaP]-administered rats were observed. Histology revealed glands with malignant epithelial cells and high nucleocytoplasm in [NMU + BaP] rats. Treatment with CP attenuated inflammation, apoptosis and restored cyto-architecture of mammary gland. Overall, CP abates mammary tumourigenesis by targeting cellular pathways of inflammation and apoptosis. [ABSTRACT FROM AUTHOR]

Simple Summary: This review aims to discuss the structure, function and dynamics of the breast gland and how changes to the function of the breast's cells can lead to different types of cancer. The human breast gland is a unique organ as most of its development occurs postnatally between menarche and menopause, a period ranging from 30 to 40 years. During this period, the monthly menstruation cycle drives the mammary gland through phases of cell proliferation, differentiation, and apoptosis, facilitated via a closely choreographed interaction between the epithelial cells and the surrounding stroma preparing the gland for pregnancy. If pregnancy occurs, maximal differentiation is reached to prepare for lactation. After lactation, the mammary gland involutes to a pre-pregnant state. These cycles of proliferation, differentiation, and involution necessitate the presence of epithelial stem cells that give rise to progenitor cells which differentiate further into the luminal and myoepithelial lineages that constitute the epithelial compartment and are responsible for the branching structure of the gland. Maintaining homeostasis and the stem cell niche depends strongly on signaling between the stem and progenitor cells and the surrounding stroma. Breast cancer is a slowly progressing disease whose initiation can take decades to progress into an invasive form. Accumulating evidence indicates that stem cells and/or progenitor cells at different stages, rather than terminally differentiated cells are the main cells of origin for most breast cancer subgroups. Stem cells and cancer cells share several similarities such as increased survival and cellular plasticity which is reflected in their ability to switch fate by receiving intrinsic and extrinsic signals. In this review, we discuss the concept of cellular plasticity in normal breast morphogenesis and cancer, and how the stromal environment plays a vital role in cancer initiation and progression. [ABSTRACT FROM AUTHOR]

Simple Summary: Studies on the tumour microenvironment show that part of the body's defence against neoplastic cells is carried out directly in the tumour through the organization of immune cellular aggregates, called tertiary lymphoid structures (TLSs). This study demonstrates the existence of TLS in canine mammary simple carcinomas, where some inflammatory infiltrates assume a follicle-like organization, especially in high-grade carcinomas and simulate the follicle of secondary lymphoid organs (SLOs). The role of TLS is controversial and it has been suggested that they contribute to an immunosuppressive environment or, on the contrary, have positive effects on neoplasm growth. Although canine mammary tumours have long been proposed as a model for studying breast cancer, there is still little research on the tumour stromal microenvironment in veterinary medicine and TLS evidence could allow for advances in understanding the process of tumour immunoediting. Neoplastic progression is influenced by the expression of tumour antigens that activate an anti-tumour immune response. Human medical studies show that this body defence is carried out in secondary lymphoid organs (SLOs) but also directly in the tumour through organized cellular aggregates that are called tertiary lymphoid structures (TLSs). However, their occurrence has different meanings in different tumour types. For example, the presence of TLSs in breast cancer is associated with the most aggressive subtypes. This paper aimed to study TLSs in canine mammary simple carcinomas. A morphological assessment of the inflammatory infiltrate was performed on H&E sections of fifty cases. Immunohistochemistry was then carried out to typify the inflammatory cells in the tumour microenvironment. Results showed that, sometimes, inflammatory infiltrates were organized in follicles close to high-grade carcinomas, simulating a lymphoid organization, as in breast cancer. Therefore, we can assume that even in canine mammary tumours, TLSs exist and they are entities to consider due to their presence in the most aggressive histotypes or tumours with a high degree of malignancy. [ABSTRACT FROM AUTHOR]

Tea polyphenols (TPs) are the main active substances in tea and they have many beneficial effects, such as anti-inflammation, antioxidant, anti-cancer and metabolic regulation effects. The quality of milk is affected by mammary gland diseases and there are substantial economic losses resulting from reduced milk production as a consequence of inflammatory injury of the mammary gland. In this study, transcriptome analysis and molecular biology techniques were used to study the effects of TPs on inflammatory injury of the mammary gland. After intervention with TPs, a total of 2085 differentially expressed genes were identified, including 1189 up-regulated genes and 896 down-regulated genes. GO analysis showed that differentially expressed genes played an important role in proton transmembrane transport, oxidation–reduction reactions and inflammatory response. KEGG enrichment suggested that differential genes were concentrated in the TGF-β pathway and active oxygen metabolism process. Experiments were performed to confirm that TPs increased SOD, CAT, T-AOC and GSH-Px content along with a reduction in MDA. Meanwhile, TPs inhibited the expression of TGF-β1 and reduced the phosphorylation of p38 and JNK. The expression of inflammatory cytokines IL-1β, IL-6 and TNF-α were significantly decreased after intervention with TPs. In summary, all the data indicated that TPs protected the mammary gland by enhancing the antioxidant capacity and down-regulating the TGF-β1/p38/JNK pathway. [ABSTRACT FROM AUTHOR]

Cytokeratins are intermediate fi lament proteins found in epithelial cells. Specifi c cytokeratin expression has been suggested to mark diff erent epithelial cell line and also to associate with mammary stem/progenitor cells. However, a comparative analysis of the expression of cytokaratins in the mammary gland during the late lactation and involution periods was limited. Here, the aim of the present study is to evaluate CK8, CK18 and CK19 expressions of the mammary gland in cows during late lactation and involution periods, immunohistochemically. Th e lobe and lobule structure were prominent in the mammary tissue in the late lactation period, but the amount of connective tissue started to increase, and epithelial cells found on the walls of the alveoli had diff erent appearances based on their secretion status. Th e walls of the ducts were covered by simple columnar epithelial cells during late lactation. CK8 and CK18 showed strong expressions in the epithelial cells of several alveoli and ducts inside the lobes and lobules in the late lactation and involution periods. In both late lactation and involution periods, there was no CK19 expression in the mammary gland tissue. In conclusion, it was demonstrated that CK8 and CK18 were expressed in the alveolar and ductal epithelial cells of the mammary gland in cows in the late lactation and involution periods, but CK19 was not expressed. Th us, our study fi ndings revealed the role of CK8 and CK18 in mammary epithelial diff erentiation and maintenance of the normal mammary epithelial layer.

Streptococcus uberis is one of the most important mastitis-causing pathogens. Although the pathogenesis and virulence factors required for the intramammary infection development are not yet well established, several putative virulence-associated genes have been described. This work aimed to investigate the presence of ten known and putative virulence-associated genes in S. uberis isolated from subclinical or clinical mastitis and its closely related species Streptococcus parauberis in 135 dairy farms in the Czech Republic. The PCR analysis detected that all the examined isolates possessed at least four virulence genes and most isolates carried eight out of ten virulence genes. All S. uberis isolates were positive for the oppF, gapC and sua genes. Among the most prevalent virulence-associated genes skc (98%) and pauA (97%) were also found. The hasA and hasB genes were always present together in 94% of the isolates. The genes cfu and lbp were detected in 6% and 2%, respectively. In the S. uberis isolates, 14 different virulence gene profiles were observed. The most frequent profile was hasA+ hasB+ sua+ skc+ pauA+ gapC+ oppF with variable hasC, observed in 86% of the tested isolates, occurring in 127 out of 135 farms. S. parauberis was identified very sporadically and, although it is closely related to S. uberis, only a rare occurrence of the examined virulence-associated genes was found.

Objective: Calliandra portoricensis (CP) is used in Nigeria for the treatment of breast diseases. We investigated the effects of fraction from CP on 7,12-dimethylbenz-[a] anthracene (DMBA)-induced mammary gland tumours. Materials and Methods: Female Wistar rats (40) were allotted into five equal groups. Group 1 served as control, group 2 received DMBA (50mg/kg), groups 3 and 4 received DMBA and were treated with CP at doses of 50 and 100 mg/kg respectively, while the fifth group received DMBA and vincristine (0.5mg/kg). The DMBA was injected intraperitoneally once while vincristine and CP were given twice and thrice per week, respectively. Results: Administration of DMBA caused a significant decrease in body weight gain by 52%. In addition, DMBA significantly increased organo-somatic weight of mammary gland by 4.0 folds. Moreso, DMBA significantly increased inflammatory and oxidative stress markers; serum interleukin-1β (IL-1β), lipid peroxidation (LPO) and myeloperoxidase (MPO) by 27%, 18% and 435%, respectively. Similarly, mammary NO (nitric oxide) and LPO were increased by 468% and 21%, respectively. In contrast, DMBA decreased the levels of apoptotic markers; BAX, caspases-3 and -9 by 20%, 15% and 18%, and mammary superoxide dismutase (SOD), catalase (CAT) and glutathione-s-peroxidase (GPx) by 45%, 51% and 68%, respectively. Histology revealed gland with malignant epithelial cells and high nucleo-cytoplasm in DMBA-administered rats. Treatment with CP at 100 mg/kg decreased LPO, MPO, IL-1β and NO by 28%, 35%; 78% and 85%, respectively, and ameliorated DMBA-induced cyto-architectural anomalies. Conclusion: Fraction of CP protects mammary gland from DMBA insults via antioxidative and anti-inflammatory mechanisms.

Tissue-specific deficiency of nicotinamide phosphoribosyl transferase (NAMPT), the rate-limiting enzyme of the nicotinamide adenine dinucleotide (NAD+)-salvage pathway, causes a decrease of NAD+ in the tissue, resulting in functional abnormalities. The NAD+-salvage pathway is drastically activated in the mammary gland during lactation, but the significance of this has not been established. To investigate the impact of NAD+ perturbation in the mammary gland, we generated two new lines of mammary gland epithelial-cell-specific Nampt- knockout mice (MGKO). LC-MS/MS analyses confirmed that the levels of NAD+ and its precursor nicotinamide mononucleotide (NMN) were significantly increased in lactating mammary glands. We found that murine milk contained a remarkably high level of NMN. MGKO exhibited a significant decrease in tissue NAD+ and milk NMN levels in the mammary gland during lactation periods. Despite the decline in NAD+ levels, the mammary glands of MGKO appeared to develop normally. Transcriptome analysis revealed that the gene profiles of MGKO were indistinguishable from those of their wild-type counterparts, except for Nampt. Although the NMN levels in milk from MGKO were decreased, the metabolomic profile of milk was otherwise unaltered. The mammary gland also contains adipocytes, but adipocyte-specific deficiency of Nampt did not affect mammary gland NAD+ metabolism or mammary gland development. These results demonstrate that the NAD+ -salvage pathway is activated in mammary epithelial cells during lactation and suggest that this activation is required for production of milk NMN rather than mammary gland development. Our MGKO mice could be a suitable model for exploring the potential roles of NMN in milk. • NAD+ metabolism in murine mammary gland is drastically activated during lactation. • Mice with impaired NAD+-salvage pathway in mammary gland were generated. • NMN is the major NAD+-related metabolite in mouse milk. • Milk NMN production is dependent on the NAD+-salvage pathway in mice. [ABSTRACT FROM AUTHOR]

The interactions of environmental compartments with epithelial cells are essential for mammary gland development and homeostasis. Currently, the direct crosstalk between the endothelial niche and mammary epithelial cells remains poorly understood. Here, we show that faciogenital dysplasia 5 (FGD5) is enriched in mammary basal cells (BCs) and mediates critical interactions between basal and endothelial cells (ECs) in the mammary gland. Conditional deletion of Fgd5 reduced, whereas conditional knockin of Fgd5 increased, the engraftment and expansion of BCs, regulating ductal morphogenesis in the mammary gland. Mechanistically, murine mammary BC-expressed FGD5 inhibited the transcriptional activity of activating transcription factor 3 (ATF3), leading to subsequent transcriptional activation and secretion of CXCL14. Furthermore, activation of CXCL14/CXCR4/ERK signaling in primary murine mammary stromal ECs enhanced the expression of HIF-1α-regulated hedgehog ligands, which initiated a positive feedback loop to promote the function of BCs. Collectively, these findings identify functionally important interactions between BCs and the endothelial niche that occur through the FGD5/CXCL14/hedgehog axis. [Display omitted] • Mammary FGD5 plays a critical role in maintaining mammary gland development • FGD5/ATF3/CXCL14 axis upregulates the proliferative activity of endothelial cells • HIF-1α in ECs promotes mammary organoid formation and reprogramming activity • FGD5/CXCL14/Hedgehog axis mediates crosstalk between basal cells and ECs Zhang et al. characterized a basal-to-endothelial signaling circuit that supports mammary development and differentiation. This research highlights the importance of mammary basal cell-expressed FGD5 in promoting EC proliferation, HIF-1α stabilization, and transcriptional activity, thereby governing mammary epithelial growth, metabolism, differentiation, and stem-like properties. [ABSTRACT FROM AUTHOR]

The transcription factor EHF is highly expressed in the lactating mammary gland, but its role in mammary development and tumorigenesis is not fully understood. Utilizing a mouse model of Ehf deletion, herein, we demonstrate that loss of Ehf impairs mammary lobuloalveolar differentiation at late pregnancy, indicated by significantly reduced levels of milk genes and milk lipids, fewer differentiated alveolar cells, and an accumulation of alveolar progenitor cells. Further, deletion of Ehf increased proliferative capacity and attenuated prolactin-induced alveolar differentiation in mammary organoids. Ehf deletion also increased tumor incidence in the MMTV-PyMT mammary tumor model and increased the proliferative capacity of mammary tumor organoids, while low EHF expression was associated with higher tumor grade and poorer outcome in luminal A and basal human breast cancers. Collectively, these findings establish EHF as a non-redundant regulator of mammary alveolar differentiation and a putative suppressor of mammary tumorigenesis. [Display omitted] • The transcription factor EHF is essential for mammary development in pregnancy • Ehf drives differentiation of progenitor cells into milk-producing alveolar cells • Ehf deletion increased tumor development in the mouse mammary gland Nightingale and Reehorst et al. identify a key role for the transcription factor EHF in mouse mammary gland development and in controlling the differentiation of mammary epithelial cells into milk-producing cells during pregnancy. They also show that Ehf is an important suppressor of tumor development in this tissue. [ABSTRACT FROM AUTHOR]

Osteopontin (OPN) is a protein synthesized by a large number of cells, and its overexpression has been associated with the development and prognosis of cancer. OPN overexpression has been claimed to be a marker for the development of bone metastasis in human cancers, but no prior research has investigated the association between OPN expression and the metastasis of canine mammary gland tumors (MGTs) and prostate cancer (PC). Therefore, we investigated OPN expression in MGTs and PC samples from 50 canine patients with or without metastasis (bone vs. other sites). Higher OPN expression was detected in primary tumor samples from animals with bone metastasis than in those without bone involvement (p = 0.0321). In MGT samples, a significantly lower survival rate was observed in patients with higher OPN expression (p = 0.0171). In animals with PC, there was a strong trend toward lower survival in animals with positive OPN expression; however, this trend was not statistically significant (p = 0.0779). From these findings, it can be concluded that OPN may be a promising target for future MGTs and PC studies because of its role in enhancing cell invasion and metastasis.

There were collected samples of mammary gland tissue from Ţurcana breed sheep, nearly aged, in lactation stage and with similar mammary gland volume/conformation. By histological and stereological evaluation were determined the relative areas of glandular parenchyma (mammary alveoli, excretion canaliculli system) and stroma (connective tissue, blood vessels, nerves). Before histological sample collecting was determined the average milk production resulted from three successive milking days. The results revealed positive correlations between average milk production and glandular parenchyma area and negative correlations between average milk production and connective stroma area from mammary gland.

The mammary glands, responsible for milk secretion, are regulated at a local level by various hormones, growth factors, non-coding RNAs, and other elements. Recent research has discovered the presence of lncRNAs in these glands, with suggestions that they may be essential for the maintenance and function of mammary glands. Besides directly controlling the gene and protein expression, lncRNAs are believed to play a significant part in numerous physiological and pathological processes. This study focused on examining the mammary gland tissues of Chinese Holstein cows, to identify and categorize long non-coding RNAs (lncRNAs). The research intended to distinguish lncRNAs in the mammary tissues of Holstein cows and contrast them between lactation and non-lactation periods. In this study, mammary gland tissues were sampled from three Holstein cows in early lactation (n = 3, 30 days postpartum) and non-lactation (n = 3, 315 days postpartum) on a large dairy farm in Jiangsu province. Mammary tissue samples were collected during early lactation and again during non-lactation. In total, we detected 1905 lncRNAs, with 57.3% being 500 bp and 612 intronic lncRNAs. The exon count for lncRNAs varied from 2 to 10. It was observed that 96 lncRNA expressions markedly differed between the two stages, with 83 genes being upregulated and 53 downregulated. Enrichment analysis results revealed that Gene Ontology (GO) analysis was primarily abundant in cellular processes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that target genes were predominantly abundant in metabolic pathways, fatty acid biosynthesis, the immune system, and glycosphingolipid biosynthesis. This study analyzed the expression profile and characteristics of lncRNAs in the mammary gland tissues of Holstein cows during both lactation and non-lactation stages, forming a foundation for further investigation into the functional roles of lncRNAs in Holstein cows throughout lactation.

ABSTRACT: Cortisol (CORT) induces mammary development in late gestation and is fundamental to the differentiation of mammary epithelial cells and lactogenesis. The objective of this study was to investigate the relationship between CORT, insulin, prolactin, growth hormone, and insulin-like growth factor-1 in milk as well as the effect of CORT on the expression of receptors of insulin (INSR), prolactin (PRLR), growth hormone (GHR); we also studied the insulin-like growth factor-1 (IGF1R), glucocorticoid (NR3C1), mineralocorticoid (NR3C2), B-cell lymphoma 2 (BCL2), BCL-2-like protein X (BAX) genes, and the apoptosis rate of mammary epithelial cells of lactating Saanen goats in vivo and in vitro. The following experiments were conducted: (1) comparing hormone release in milk and blood after ACTH or a placebo administration; (2) evaluating the effect of acute CORT increases in mammary gland expression and milk yield in vivo; and (3) evaluating the effect of a chronic increase in CORT concentration in epithelial mammary cell apoptosis in vitro. In vivo, ACTH administration significantly increased CORT release but did not affect insulin, prolactin, growth hormone, and insulin-like growth factor-1 release in plasma and milk versus placebo. The results show also that a low CORT release after ACTH administration increased the expression of GHR and PRLR genes in the mammary tissue. Indeed, CORT release significantly increased the milk yield from goats subjected to ACTH versus goats subjected to the placebo. However, a higher amount of CORT added in vitro upregulated the NR3C1, GHR, PRLR, and BAX genes and downregulated the IGF1R and INSR genes, which could negatively modulate the apoptosis of mammary epithelial cells. Finally, the effect of CORT in vivo after ACTH administration demonstrated the increased expression of the PRLR and GHR genes, which may improve epithelial cell responsiveness and be associated with the positive effect of CORT observed on milk yield at mid-end lactation.

ABSTRACT: Mastitis has a high incidence in dairy cows. Experimental infection with Escherichia coli increased the number of leukocytes in milk and the gene expression of the chemokine receptor CXCR4 in mammary gland tissues. A link between CXCR4 expression and lipopolysaccharide sensing was demonstrated in other species using in vitro models. The receptor that binds the chemokine stomal cell-derived factor 1 might be associated with the inflammatory response in bovine mammary glands. However, studies in cows are rare, and data on the localization of CXCR4 in bovine mammary glands and its distribution in bovine leukocytes are lacking. Fatty acids (FA) affect the inflammatory response. In human peripheral blood monocytes, exposure to conjugated linoleic acids (CLA) decreases the expression of CXCR4, leading to a decreased inflammatory response in these cells. In this study, we analyzed the expression of CXCR4 in the mammary glands of dairy cows by immunohistochemistry (n = 5) and laser capture microdissection followed by qualitative PCR (n = 3). We characterized the surface expression of CXCR4 on bovine leukocytes, including monocyte subpopulations, first by flow cytometry (n = 5) and then confirmed these results by Western blotting (n = 3). Rumen fistulated dairy cows (n = 4; 126 ± 4 d in milk) were fitted with abomasal infusion tubes, arranged in a 4 × 4 Latin square design, and supplemented for 6 wk twice daily with rising doses of FA followed by a 3-wk washout period. Then, CXCR4 expression on leukocytes was analyzed. The cows received a corn-based diet and were supplemented with coconut oil delivering medium-chain FA (38 g/d), linseed-safflower oil mix delivering n-3 FA (EFA, 39 g of linseed oil and 2 g of safflower oil per day), Lutalin (cis-9,trans-11 and trans-10,cis-12 CLA, 5 g/d; BASF), and EFA + CLA. In the bovine mammary gland, the epithelial cells of the lactiferous duct, but not alveolar epithelial cells, showed clear CXCR4 protein and mRNA signals. Among the leukocyte subsets, monocytes displayed the highest percentage of CXCR4-positive cells (87%), whereas circulating neutrophils showed almost no CXCR4 surface expression (3%) but stored the receptor intracellularly. The percentage of CXCR4-positive leukocytes was not affected by the different FA supplements, but FA supplementation reduced the receptor abundance per cell (40% on average). In conclusion, CXCR4 was clearly detected in the lactiferous duct cells of the mammary gland but not in the alveolar epithelial cells. Compared with other leukocytes, bovine monocytes showed the highest signal intensity of CXCR4 on their surface, whereas granulocytes stored CXCR4 intracellularly. Supplementation with all the FA reduced the surface expression of CXCR4 per leukocyte and could therefore potentially affect the inflammatory status associated with the surface expression of CXCR4. The importance of our observations should be verified in cows with mastitis in the future.

Pueraria candollei var. mirifica (Fabaceae) root (PMR) has recently been developed as a potential selective estrogen receptor modulator (SERM) in menopausal women. Nowadays, many premenopausal women also take dietary PMR supplements, however, the exact biological effects of PMR have not been evaluated. This study included the application of the OECD guideline 407 for the assessment of 28-day oral exposure to PMR on pituitary-ovarian (PO) axis function and metabolic parameters in the premenopausal rat model. Ovary-intact adult rats were orally administrated with 10, 100, 750, 1000, and 1500 mg/kg body weight (BW)/day of PMR powder. The positive estrogenic group was given 2 mg 17β-estradiol (E2)/kg BW/day. Serum levels of reproductive hormones, lipid and thyroid parameters, estrous cycle determination, and histomorphometric and histopathological evaluations of the anterior pituitary, ovary, uterus, vagina, mammary gland, and liver were investigated. PMR displayed neutral effects on uterine, vaginal, and body weights, and circulating E2 and prolactin levels. PMR exerted E2-like effects by i) reducing ovarian and increasing hepatic weights, ii) decreasing serum gonadotropins, iii) lowering serum lipids without altering thyroid parameters, iv) increasing the prevalence of abnormal estrous cycles with prolonged estrus, v) increasing nuclear diameter of anterior pituitary cells, vi) decreasing ovarian size and follicular numbers and increasing follicular degeneration, vii) thickening of uterine myometrium and luminal epithelium, and vaginal epithelium, and viii) induction of mammary alveolar hyperplasia and ductal secretion. Unlike E2, the appearance of very small numbers of focal microvesicular steatosis in hepatocytes demonstrated mild toxicity at high PMR doses. This is the first report that high-dose PMR exerted actions exactly like E2 on gonadotrope-ovarian axis function and histology, lipid, and thyroid parameters without affecting uterine and vaginal growth in ovary-intact rats according to OECD guidelines.

Humans are exposed to different kinds of environmental contaminants or drugs throughout their lifetimes. The widespread presence of these compounds has raised concerns about the consequent adverse effects on lactating women. The constitutive androstane receptor (CAR, Nr1i3) is known as a xenobiotic sensor for environmental pollution or drugs. In this study, the model environmental chemical 1, 4-bis [2-(3, 5-dichloropyridyloxy)] benzene, TCPOBOP (TC), which is a highly specific agonist of CAR, was used to investigate the effects of exogenous exposure on lactation function and offspring health in mice. The results revealed that TC exposure decreased the proliferation of mammary epithelial cells during pregnancy. This deficiency further compromised lobular-alveolar structures, resulting in alveolar cell apoptosis, as well as premature stoppage of the lactation cycle and aberrant lactation. Furthermore, TC exposure significantly altered the size and number of milk lipid droplets, suggesting that TC exposure inhibits milk lipid synthesis. Additionally, TC exposure interfered with the milk lipid metabolism network, resulting in the inability of TC-exposed mice to efficiently secrete nutrients and feed their offspring. These findings demonstrated that restricted synthesis and secretion of milk lipids would indirectly block mammary gland form and function, which explained the possible reasons for lactation failure and retarded offspring growth.

Extracellular vesicles (EVs) are secreted by many cell types and are increasingly investigated for their role in human diseases including cancer. Here we focus on the secretion and potential physiological function of non-pathological EVs secreted by polarized normal mammary epithelial cells. Using a transwell system to allow formation of epithelial polarity and EV collection from the apical versus basolateral compartments, we found that impaired secretion of EVs by knockdown of RAB27A or RAB27B suppressed the establishment of mammary epithelial polarity, and that addition of apical but not basolateral EVs suppressed epithelial polarity in a dose-dependent manner. This suggests that apical EV secretion contributes to epithelial polarity, and a possible mechanism is through removal of certain intracellular molecules. In contrast, basolateral but not apical EVs promoted migration of mammary epithelial cells in a motility assay. The protein contents of apical and basolateral EVs from MCF10A and primary human mammary epithelial cells were determined by mass spectrometry proteomic analysis, identifying apical-EV-enriched and basolateral-EV-enriched proteins that may contribute to different physiological functions. Most of these proteins differentially secreted by normal mammary epithelial cells through polarized EV release no longer showed polarized secretion in MCF10A-derived transformed epithelial cells. Our results suggest an essential role of EV secretion in normal mammary epithelial polarization and distinct protein contents and functions in apical versus basolateral EVs secreted by polarized mammary epithelia.

Adipose tissue depots can exist in close association with other organs, where they assume diverse, often non-traditional functions. In stem cell-rich skin, bone marrow, and mammary glands, adipocytes signal to and modulate organ regeneration and remodeling. Skin adipocytes and their progenitors signal to hair follicles, promoting epithelial stem cell quiescence and activation, respectively. Hair follicles signal back to adipocyte progenitors, inducing their expansion and regeneration, as in skin scars. In mammary glands and heart, adipocytes supply lipids to neighboring cells for nutritional and metabolic functions, respectively. Adipose depots adjacent to skeletal structures function to absorb mechanical shock. Adipose tissue near the surface of skin and intestine senses and responds to bacterial invasion, contributing to the bodys innate immune barrier. As the recognition of diverse adipose depot functions increases, novel therapeutic approaches centered on tissue-specific adipocytes are likely to emerge for a range of cancers and regenerative, infectious, and autoimmune disorders.

Abstract Background Staphylococcus aureus (S. aureus) mastitis is one of the most difficult diseases to treat in lactating dairy cows worldwide. S. aureus with different lineages leads to different host immune responses. Long non-coding RNAs (lncRNAs) are reported to be widely involved in the progress of inflammation. However, no research has identified stable lncRNAs among different S. aureus strain infections. In addition, folic acid (FA) can effectively reduce inflammation, and whether the inflammatory response caused by S. aureus can be reduced by FA remains to be explored. Methods lncRNA transcripts were identified from Holstein mammary gland tissues infected with different concentrations of S. aureus (in vivo) and mammary alveolar cells (Mac-T cells, in vitro) challenged with different S. aureus strains. Differentially expressed (DE) lncRNAs were evaluated, and stable DE lncRNAs were identified in vivo and in vitro. On the basis of the gene sequence conservation and function conservation across species, key lncRNAs with the function of potentially immune regulation were retained for further analysis. The function of FA on inflammation induced by S. aureus challenge was also investigated. Then, the association analysis between these keys lncRNA transcripts and hematological parameters (HPs) was carried out. Lastly, the knockdown and overexpression of the important lncRNA were performed to validate the gene function on the regulation of cell immune response. Results Linear regression analysis showed a significant correlation between the expression levels of lncRNA shared by mammary tissue and Mac-T cells (P

The Hippo pathway is a highly conserved kinase cascade in mammals with the proteins YAP and TAZ as its most important downstream effectors that shuttle between cytoplasma and nucleus. It has a crucial role in processes such as embryogenesis, organ size control, homeostasis and tissue regeneration, where mechanosensing and/or cell-cell interactions are involved. As the pathway is associated with many essential functions in the body, its dysregulation is related to many diseases. In contrast to human pathology, a PubMed-search on Hippo, YAP/TAZ and companion animals (horse, equine, dog, canine, cat, feline) retrieved few publications. Because of its high level of functional conservation, it is anticipated that also in veterinary sciences aberrant Hippo YAP/TAZ signaling would be implicated in animal pathologies. Publications on Hippo YAP/TAZ in companion animals are mainly in cats and dogs and related to oncology. Here, we emphasize the important role of YAP/TAZ in liver diseases. First the liver has a remarkable regeneration capacity and a strict size control and the liver has a moderate liver cell renewal (homeostasis). The last years numerous papers show the importance of YAP/TAZ in hepatocellular carcinoma (HCC), hepatocyte differentiation and bile duct epithelial (BEC) cell survival. YAP/TAZ signaling is involved in activation of hepatic stellate cells crucial in fibrogenesis. The availability of drugs (e.g. verteporfin) targeting the YAP/TAZ pathway are described as is their potential usage in veterinary medicine. The aim of this overview is to stimulate researchers’ and clinicians’ interest in the potential role of Hippo YAP/TAZ signaling in veterinary medicine.

Objective: The objective of this study was to obtain an insight into the role of the vascular endothelial growth factor (VEGF) in pregnancy-associated mammary epithelial development and angiogenesis. However, we examined the primary VEGF receptor (VEGFR-2) in the mouse mammary cycle. Materials and Methods: The virgin (1012 weeks), days 10 and 18 of pregnancy (P-10 and P-18), days 0, 5, 10, and 20 of lactation (L-0, L-5, L-10, and L-20), and days 5 and 10 of post-weaning (W-5 and W-10) stage were all used in this study. Immunohistochemistry and Western blotting were carried out on mammary tissues taken from three mice at each stage. Results: VEGFR-2 was detected immunohistochemically in the cytoplasm of mammary epithelial and endothelial cells. Immunostaining for VEGFR-2 was consistently positive in mammary endothelial cells across all stages, whereas staining intensity in epithelial cells varied across the mammary cycle. Additionally, immunoblot analysis indicated a 220 kDa unique band of VEGFR-2 protein at all stages of the mammary cycle, with the maximum expression reported toward the end of pregnancy and gradually decreasing toward the end of lactation. Conclusion: In conclusion, the presence of VEGFR-2 in the mammary epithelium in addition to the endothelium suggests that VEGF plays an autocrine and paracrine role in the development, proliferation, and differentiation of the mammary epithelium during pregnancy. [J Adv Vet Anim Res 2021; 8(4.000): 581-588]

Cow mastitis is one of the main factors of economic damage in modern animal husbandry. It is registered to affect almost everywhere, taking into account the subclinical form from 30% to 50% of the livestock per year. Economic losses of farms from the diseases of cows with mastitis are due to a decrease in milk productivity, precocious cow disposal, a decrease in the grade and sale price of market milk, and treatment costs. This study aimed to use a safer method in the prevention and control of mastitis in cows, and vaccinations could be a solution to this problem. Vaccination promotes acquired immunity to a specific pathogen and also has few side effects. A bacteriological study of clinical and subclinical forms of mastitis was conducted to study the etiology of mastitis in cows in various farms of Kazakhstan. A total of 1,068 milk samples from 767 cows were examined. The studies were carried out according to "Guidelines for bacteriological studies of milk and udder secretions of cows". The primary selection of cultures was carried out based on growth characteristics on media and microscopy of preparations from individual colonies. Morphological, cultural, and biochemical properties of the isolated cultures were studied according to generally accepted schemes. Identification of the selected cultures was carried out using Bergey's determinant. The strain numbers of Staphylococci, Streptococci, Escherichia, Klebsiella, Diplococci, and Protea were 590 (55.2%), 240 (22.4%), 151 (14.1%), 50 (4.7%), 24 (2.3%), and 13 (1.3%), respectively. The greatest strain numbers of Staphylococci (n=351) and Streptococci (n=129) were isolated from cow's milk with subclinical mastitis. The effectiveness of the polyvalent vaccine used was determined by the manifestation of clinical and subclinical forms of mastitis. Out of 600 immunized cows, 9 (1.5%) and 13 (2.3%) animals developed subclinical and clinical mastitis, respectively. Furthermore, out of 150 cows taken into control, 12 (8%) and 10 (6.6%) animals developed subclinical and clinical mastitis, respectively. Furthermore, out of 12 cows with clinical mastitis, 5 cows previously had a subclinical form. Vaccination takes a significant place in the control of infectious diseases. The success of vaccine prevention depends on the quality of vaccines and timely vaccination coverage of threatened populations. Modern immunology and vaccine prevention have summed up the theoretical basis and outlined ways to improve vaccines in the direction of creating new harmless effective vaccines.

Sheep milk production is a dynamic and multifactorial trait regulated by diverse biological mechanisms. To improve the quality and production of sheep milk, it is necessary to understand the underlying non-coding transcriptomic mechanisms. In this study, ribonucleic acid-sequencing (RNA-seq) was used to profile the expression of microRNAs (miRNAs) and circular RNAs (circRNAs) in the sheep mammary gland at three key lactation time points (perinatal period, PP; early lactation, EL; and peak lactation, PL). A total of 2,369 novel circRNAs and 272 miRNAs were profiled, of which 348, 373, and 36 differentially expressed (DE) circRNAs and 30, 34, and 7 DE miRNAs were detected in the comparison of EL vs. PP, PL vs. PP, and PL vs. EL, respectively. A series of bioinformatics analyses including functional enrichment, machine learning prediction, and competing endogenous RNA (ceRNA) network analyses were conducted to identify subsets of the potential candidate miRNAs (e.g., oar_miR_148a, oar_miR_362, and oar_miR_432) and circRNAs (e.g., novel_circ_0011066, novel_circ_0010460, and novel_circ_0006589) involved in sheep mammary gland development. Taken together, this study offers a window into the dynamics of non-coding transcriptomes that occur during sheep lactation and may provide further insights into miRNA and circRNA that influence sheep mammary gland development.

In mothers who are nursing their infants, increased clearance of plasma metabolites into the mammary gland may reduce ectopic lipid in the liver. No study to date has investigated the role of lactation on liver lipid synthesis in humans, and we hypothesized that lactation would modify fatty acid and glucose handling to support liver metabolism in a manner synchronized with the demands of milk production. Lactating (n = 18) and formula-feeding women (n = 10) underwent metabolic testing at 6-week postpartum to determine whether lactation modified intrahepatic triacylglycerols (IHTGs), measured by proton magnetic resonance spectroscopy. Subjects ingested oral deuterated water to measure fractional de novo lipogenesis (DNL) in VLDL-TG during fasting and during an isotope-labeled clamp at an insulin infusion rate of 10 mU/m2/min. Compared with formula-feeding women, we found that lactating women exhibited lower plasma VLDL-TG concentrations, similar IHTG content and similar contribution of DNL to total VLDL-TG production. These findings suggest that lactation lowers plasma VLDL-TG concentrations for reasons that are unrelated to IHTG and DNL. Surprisingly, we determined that the rate of appearance of nonesterified fatty acids was not related to IHTG in either group, and the expected positive association between DNL and IHTG was only significant in formula-feeding women. Further, in lactating women only, the higher the prolactin concentration, the lower the IHTG, while greater DNL strongly associated with elevations in VLDL-TG. In conclusion, we suggest that future studies should investigate the role of lactation and prolactin in liver lipid secretion and metabolism.

Supernumerary or extra teats in ruminants are defined as any teats that exceed the normal number. The presence of five or six teats is not normal in a cow or goat, but it is not unusual. Which of these are extra? It is usually very obvious; sometimes it is helpful to look at the placement, size and sphincter development of all teats to identify normal versus extra. Most additional nipples in goats are "blind"and are not attached to the mammary tissue. An extra nipple is not able to produce milk. Blind teats are often found in pairs. It is not uncommon in cattle or goats to find a pair of "buttonlike" protrusions on the hindquarters or a few less developed hanging teats next to the functional ones. Causing little more than an unsightly rear udder image, blind teats in a commercial cattle or goat herd are usually not a problem [ABSTRACT FROM AUTHOR]

Due to their endocrine disruption properties, phthalate plasticizers such as di(2-ethylhexyl) phthalate (DEHP) can affect the hormone-dependent development of the mammary gland. Over the past few years, DEHP has been partially replaced by 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) which also have potential endocrine disrupting properties. The goal of the present study is to understand the impact of a gestational and lactational exposure to DEHP and DINCH on mammary gland development using Sprague Dawley rats. Both plasticizers altered the adipocytes of the mammary gland fat pad of adult progeny, as demonstrated by a decrease in their size, folding of their membrane, and modulations of the lipid profiles. DEHP treatments decreased the expression of Rxrα and Scd1 at the low and high dose, respectively, but did not affect any of the other genes studied. DINCH modulation of lipid metabolism could be observed at puberty by a decreased expression of genes implicated in triglyceride synthesis, lipid transport, and lipolysis, but by an increased expression of genes of the β-oxidation pathway and of genes involved in lipid storage and fatty acid synthesis at adulthood, compared with control and DEHP-treated rats. A strong upregulation of different inflammatory markers was observed following DINCH exposure only. Together, our results indicate that a gestational and lactational exposure to DINCH has earlier and more significant effects on lipid homeostasis, adipogenesis, and the inflammatory state of the adult mammary gland than DEHP exposure. The long-term consequence of these effects on mammary gland health remained to be determined. [ABSTRACT FROM AUTHOR]

Simple Summary: The udder health of sows is most important to raise healthy piglets. The aim of the study was to investigate a possible advantage of infrared thermography and ultrasonography over the clinical examination of the udder of sows. For this purpose, both clinically healthy sows with inconspicuous udders on palpation before and after birth (n = 35) and sows at the time of weaning (n = 107) were examined. Images of thermography and ultrasound revealed no pathological alterations in the clinically healthy sows. A physiological statistically significant increase in the udder surface temperature and the thickness of the parenchyma during the three weeks ante partum was observed. After weaning, abnormalities in the appearance of roundish nodules of the parenchyma were detected sonographically in 10.3% of the examined sows, while the demonstrated nodules were unrecognised clinically in two out of eleven sows. The changes could also be demonstrated thermographically because of a statistically significant lower surface temperature above the nodules compared to the remaining skin of the mammary gland. However, scratches on the udder skin showed similar temperature changes. Therefore, thermographic images without prior inspection of the udder can lead to misinterpretation. The aim of the study was to examine whether the use of infrared thermography and ultrasonography can complement or replace the clinical examination of the sows' mammary glands for pathological alterations. Sows of different parities with inconspicuous udders on palpation before and after birth (n = 35) and sows at the time of weaning (n = 107) were examined. Thermal images were taken from both sides of the udder, while ultrasound pictures were taken from four sides of the respective mammary glands. Within three weeks before birth, a statistically significant increase in the average surface temperature of the glands of about 1.54 °C and of the thickness of the parenchyma of about 1.39 cm could be observed. After weaning, in 10.3% of the examined sows, roundish hyperechogenic nodules were detected sonographically in the glands´ parenchyma. The average skin temperature above the nodules was 1.24 °C lower compared to the total skin area of the altered complex. However, scratches on the udder skin showed similar temperature changes. In two sows, the nodules remained undetected during the clinical examination. Therefore, sonography seems to be superior compared to clinical and thermographic investigations, although it proved to be very time-consuming. [ABSTRACT FROM AUTHOR]

Simple Summary: In dairy buffaloes, the efficiency of the milking process mostly depends on the anatomical and physiological differences found in this species when compared to cattle from the genus Bos. Milk quality is influenced by individual and environmental characteristics such as health, diet, handling, and the use of exogenous hormones such as oxytocin, elements that can alter the dam's performance. The present review aims to integrate the anatomical characteristics of the mammary gland and the neurophysiology of milk ejection to understand the milking capacity of the water buffalo. The present review aims to integrate the anatomical characteristics of the mammary gland and the neurophysiology of milk ejection to understand the milking capacity of the water buffalo. Since one of the main uses of this species is milk production, this article will analyze the controversies on the use of oxytocin as a stimulant during milking as well as the existing alternatives that farmers apply to promote correct stimulation during milk letdown. According to the available literature, the efficiency of the milking process, the quality of the milk, and the health of the animals are elements that require the consideration of species-specific characteristics to enhance the performance of buffaloes. The incorporation of technological innovations and competitive strategies could contribute to a better understanding of water buffalo in the milk industry. [ABSTRACT FROM AUTHOR]

The work on creating an iodine-containing preparation for transdermal use was completed, and its physicochemical properties, stability during long-term storage, local irritant effect, exfoliating ability, harmlessness for the body, therapeutic effectiveness for mastitis and udder diseases in cows were studied. The drug of the new generation – uberdermin- results from the interaction of polyiodbismuthsulfamide (PIVS) and dimethyl sulfoxide in a ratio of 10: 1. It is a pasty product of orange color, with a slight garlic smell and a bitter, astringent taste. The study of the physical stability of uberdermin lasted 12 months; he did not reveal significant changes in the controlled indicators (color, smell, taste, consistency, homogeneity, impurities). Cutaneous applications of uberdermin did not reveal an irritating effect of the drug on the glandular tissue of the udder of cows; this is confirmed by counting the number of somatic cells in milk and lysozyme titer. Skin resorptive capacity of uberdermin, visual control of the speed of its discoloration after an application was completed 2.3 times faster compared to PIVS. Control of the translocation of active components of uberdermin in the parenchyma of the mammary gland of lactating cows was based on changes in the concentration of molecular iodine in milk after applying the drug to the skin. of the udder. As it turned out, already 6 hours after its application in a therapeutic dose, the concentration of iodine in milk increased almost twice. Uberdermin showed relatively high antibacterial activity against all tested strains, but the advantages over PIVS are not obvious. Treatment of dry cows with purulent catarrhal mastitis by uberdermin ensured 100% recovery, and 2–3 applications of the drug were needed for the course of treatment; it is two times less than the pre-dry period. Research studies on using uberdermin for udder diseases (frostbite of the tips, bruises, wounds, skin cracks) indicate the prospects of thorough research in this direction. [ABSTRACT FROM AUTHOR]

Background: Bovine metabolism undergoes significant changes during subclinical mastitis, but the relevant molecular mechanisms have not been elucidated. In this study we investigated the changes in milk microbiota and metabolites after intramammary infusion of matrine-chitosan hydrogels (MCHs) in cows with subclinical mastitis. Methods: Infusions were continued for 7 days, and milk samples were collected on days 1 and 7 for microbiome analysis by 16S rRNA gene sequencing and metabolite profiling by liquid chromatography-mass spectrometry. Results: MCHs significantly decreased the somatic cell count on day 7 compared to day 1, and the Simpson index indicated that microbial diversity was significantly lower on day 7. The relative abundance of Aerococcus, Corynebacterium_1, Staphylococcus and Firmicutes was significantly decreased on day 7, while Proteobacteria increased. In the milk samples, we identified 74 differentially expressed metabolites. The MCHs infusion group had the most significantly upregulated metabolites including sphingolipids, glycerophospholipids, flavonoids and fatty acyls. The mammary gland metabolic pathways identified after MCHs treatment were consistent with the known antimicrobial and anti-inflammatory properties of matrine that are associated with glycerophospholipid metabolism and the sphingolipid metabolic signaling pathways. Conclusion: These insights into the immunoregulatory mechanisms and the corresponding biological responses to matrine demonstrate its potential activity in mitigating the harmful effects of bovine mastitis. [ABSTRACT FROM AUTHOR]

Toll-like receptor 2 (TLR2) plays a crucial role in bacterial recognition and the host immune response during infection. However, its function and downstream biological processes (BPs) in the mammary glands (MGs) of Holstein cows with clinical mastitis (CM) are not fully understood. This study aimed to comprehensively identify the BPs and differentially expressed proteins (DEPs) associated with the bacterial response and TLR2 using data-independent acquisition (DIA) proteomic data. A possible mechanism for the action of TLR2 was proposed, and the results suggested that the expression levels of TLR2 and caspase 8 (CASP8) were positively correlated with the apoptosis of MGs. The expression patterns of TLR2 and TEK receptor tyrosine kinase 2 (Tie2) were negatively correlated with angiogenesis. These results indicated that TLR2 might promote apoptosis in mammary epithelial cells (MECs) and vascular endothelial cells (VECs) via upregulation of CASP8 expression, and inhibition of angiogenesis in VECs via downregulation of Tie2 expression in dairy cows with CM. In conclusion, TLR2 is associated with inflammation, apoptosis, and angiogenesis in the MGs of dairy cows with bacteria-induced mastitis. These results contribute to a deeper understanding of the pathogenic mechanisms and provide the knowledge needed for developing the prevention and treatment of dairy mastitis. [ABSTRACT FROM AUTHOR]

Nanoparticles are applied as versatile platforms for drug/gene delivery in many applications owing to their long‐retention and specific targeting properties in living bodies. However, the delivery mechanism and the beneficial effect of nanoparticle‐retention in many organisms remain largely uncertain. Here, the transport and metabolism of mineral nanoparticles in mammary gland during lactation are explored. It is shown that maternal intravenous administration of iron oxide nanoparticles (IONPs; diameter: ≈11.0 nm, surface charge: −29.1 mV, surface area: 1.05 m2 g−1) provides elevated iron delivery to mammary gland and increased iron secretion into breast milk, which is inaccessible by classical iron‐ion transport approaches such as the transferrin receptor‐mediated endocytic pathway. Mammary macrophages and neutrophils are found to play dominant roles in uptake and delivery of IONPs through an unconventional leukocyte‐assisted iron secretion pathway. This pathway bypasses the tight iron concentration regulation of liver hepcidin‐ferroportin axis and mammary epithelial cells to increase milk iron‐ion content derived from IONPs. This work provides keen insight into the metabolic pathway of nanoparticles in mammary gland while offering a new scheme of nutrient delivery for neonate metabolism regulation by using nanosized nutrients. [ABSTRACT FROM AUTHOR]

Calorie restriction enhances stem cell self-renewal in various tissues, including the mammary gland. We hypothesized that similar to their intestinal counterparts, mammary epithelial stem cells are insulated from sensing changes in energy supply, depending instead on niche signaling. The latter was investigated by subjecting cultures of mammary epithelial stem cells for 8 days to in vivo paracrine calorie-restriction signals collected from a 4-day-conditioned medium of individual mammary cell populations. Conditioned medium from calorie-restricted non-epithelial cells induced latent cell propagation and mammosphere formation—established markers of stem cell self-renewal. Combined RNA-Seq, immunohistochemistry and immunofluorescence analyses of the non-epithelial population identified macrophages and secreted CSF1 as the energy sensor and paracrine signal, respectively. Calorie restriction-induced pStat6 expression in macrophages suggested that skewing to the M2 phenotype contributes to the sensing mechanism. Enhancing CSF1 signaling with recombinant protein and interrupting the interaction with its highly expressed receptor in the epithelial stem cells by neutralizing antibodies were both affected stem cell self-renewal. In conclusion, combined in vivo, in vitro and in silico studies identified macrophages and secreted CSF1 as the energy sensor and paracrine transmitter, respectively, of the calorie restriction-induced effect on mammary stem cell self-renewal. [ABSTRACT FROM AUTHOR]

Donkey milk is consumed by humans for its nutritional and therapeutic properties. MicroRNAs (miRNAs) and messenger RNAs (mRNAs) have been implicated in the regulation of milk component synthesis and mammary gland development. However, the regulatory profile of the miRNAs and mRNAs involved in lactation in donkeys is unclear. We performed mRNA-seq and miRNA-seq and constructed coexpression regulatory networks for the mammary glands during the lactating and nonlactating period of jennies. We identified 3144 differentially expressed (DE) mRNAs (987 upregulated mRNAs and 2157 downregulated mRNAs) and 293 DE miRNAs (231 upregulated miRNAs and 62 downregulated miRNAs) in the lactating group compared to the nonlactating group. The DE miRNA target mRNA were significantly associated with pathways related to RNA polymerase, glycosphingolipid biosynthesis, mRNA surveillance, ribosome biogenesis in eukaryotes, glycerophospholipid metabolism, Ras signaling, and the fly hippo signaling pathway. The mRNA–miRNA coregulation analysis showed that novel-m0032-3p, miR-195, miR-26-5p, miR-23-3p, miR-674-3p, and miR-874-3p are key miRNAs that target mRNAs involved in immunity and milk lipid, protein, and vitamin metabolism in the jenny mammary gland. Our results improve the current knowledge of the molecular mechanisms regulating bioactive milk component metabolism in the mammary glands and could be used to improve milk production in donkeys. [ABSTRACT FROM AUTHOR]

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