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1.
J Anim Sci Biotechnol ; 15(1): 124, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39350237

ABSTRACT

BACKGROUND: Although several cell culture systems have been developed to investigate the function of the mammary gland in dairy livestock, they have potential limitations, such as the loss of alveolar structure or genetic and phenotypic differences from their native counterparts. Overcoming these challenges is crucial for lactation research. Development of protocols to establish lactating organoid of livestock represents a promising goal for the future. In this study, we developed a protocol to establish a culture system for mammary organoids in dairy goats to model the mammary gland development and lactation process. RESULTS: The organoids cultured within an extracellular matrix gel maintained a bilayer structure that closely resembled the native architecture of mammary tissue. The expansion of mammary organoids was significantly promoted by growth factors containing epidermal growth factor and fibroblast growth factor 2 whereas the proliferative index of the organoids was significantly inhibited by the treatment with WNT inhibitors. Upon stimulation with a lactogenic medium containing prolactin, the mammary organoids exhibited efficient lactation, characterized by the accumulation of lipid droplets in the lumen space. The lactation could be sustained for more than 3 weeks. Importantly, the expression patterns of genes related to fatty acid synthesis and milk proteins in lactating organoids closely mirrored those observed in mammary tissues. These observations were confirmed by data from proteomic analysis that the bulk of milk proteins was produced in the lactating organoids. CONCLUSION: This study is the first to establish a mammary organoid culture system modeling the mammary gland development and lactation process in ruminants. The efficient induction of lactation in ruminant mammary organoids holds promises for advancing the field of cell-based milk bio-manufacture in the food industry.

2.
Vet Med Sci ; 10(6): e70027, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39294888

ABSTRACT

BACKGROUND AND AIMS: The objective of this case report was to describe an ultrasound-guided, minimally invasive method for longitudinal mammary gland tissue collection from the bovine species. MATERIALS AND METHODS: Biopsies were performed on 14 8-week-old calves and 113 10-week-old calves. A subset of 36 animals had repeated mammary gland biopsies through the first lactation. Mammary gland biopsies were performed using a disposable biopsy punch. The technique was also performed on multiparous cows on other independent research trials. RESULTS: One-hundred and thirteen animals healed from the 10-week biopsies with no complications. Of the 36 animals that received repeated biopsies, one developed mastitis due to premature suture removal and one had recurring mastitis in all quarters. Thirty-three animals underwent all biopsies during gestation. Thirty of the original 36 are currently in lactation and still undergoing repeated biopsies. The method has also been successfully replicated on multiparous cows in separate studies. DISCUSSION AND CONCLUSION: The described technique is a safe, reliable method for cattle mammary gland biopsies beginning at eight weeks of age and can be utilized to obtain repeated tissue collection from individual animals. The technique is also straightforward to perform and utilizes simple tools while providing acceptable amounts of tissue for most applications, with low risk for infection and long-term tissue damage.


Subject(s)
Mammary Glands, Animal , Animals , Cattle , Female , Biopsy/veterinary , Tissue and Organ Harvesting/veterinary , Tissue and Organ Harvesting/methods , Ultrasonography, Interventional/veterinary , Ultrasonography, Interventional/methods
3.
Vaccine ; 42(26): 126385, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39326211

ABSTRACT

Mastitis is a major issue for the dairy industry. Despite multiple attempts, the efficacy of available mastitis vaccines is limited and this has been attributed to their incapacity to trigger robust cell-mediated immunity. Yeasts have recently been identified as promising antigen vectors capable of inducing T-cell responses, surpassing the antibody-biased mechanisms elicited by conventional adjuvanted vaccines. In this study, we combine in vitro, ex vivo, and in vivo approaches to evaluate the potential of the yeast Saccharomyces cerevisiae as a platform for novel vaccines against bovine mastitis. We demonstrate that S. cerevisiae is safe for intramuscular and intramammary immunisation in dairy cows. Vaccination resulted in a significant increase of IFNγ and IL-17 responses against the yeast platform but not against the vaccine antigen. These observations highlight that strategies to counterbalance the immunodominance of S. cerevisiae antigens are necessary for the development of successful vaccine candidates.

4.
Vet Res Commun ; 2024 Sep 28.
Article in English | MEDLINE | ID: mdl-39340734

ABSTRACT

In male cats, as in men, mammary carcinomas are rarely reported. However, like in females, hormonal therapy is a significant risk factor. This study reports the case of an 11-year-old male cat with multiple mammary tumours and a history of long-term medroxyprogesterone acetate therapy for the suppression of sexual behaviour, along with a brief review of the literature. Complete surgical removal of the right mammary chain and the ipsilateral inguinal lymph nodes was performed, and all tissues were submitted for histology. Histological examination revealed the presence of a tumour in the third and fourth mammary glands, consisting of neoplastic cells arranged in various structures, including tubulopapillary and tubular structures, sometimes cystically dilated, and solid areas. The inguinal lymph nodes were also involved. The morphology was consistent with a diagnosis of mammary carcinoma, tubulopapillary type, with nodal metastases. Immunohistochemistry revealed that tumour cells were positive for cytokeratin (clones AE1/AE3), while stromal cells were positive for vimentin (clone V9). The proliferation marker Ki-67, evaluated on both the primary tumour and the nodal metastases, was strongly expressed in the nuclei of neoplastic cells, with a Ki-67 proliferation index of 8.9% and 20% for the primary tumour and the metastases, respectively. This case highlights the importance of considering the possibility of malignant mammary tumours not only in female but also in male cats with a history of long-term hormonal treatment for suppression of sexual behaviour.

5.
Cell Rep ; 43(9): 114762, 2024 09 24.
Article in English | MEDLINE | ID: mdl-39321020

ABSTRACT

Adult mammary stem cells (aMaSCs) are vital to tissue expansion and remodeling during the process of postnatal mammary development. The protein C receptor (Procr) is one of the well-identified surface markers of multipotent aMaSCs. However, an understanding of the regulatory mechanisms governing Procr's protein stability remains incomplete. In this study, we identified Glycoprotein m6a (Gpm6a) as a critical protein for aMaSC activity modulation by using the Gpm6a knockout mouse model. Interestingly, we determined that Gpm6a depletion results in a reduction of Procr protein stability. Mechanistically, Gpm6a regulates Procr protein stability by mediating the formation of lipid rafts, a process requiring Zdhhc1 and Zdhhc2 to palmitate Gpm6a at Cys17,18 and Cys246 sites. Our findings highlight an important mechanism involving Zdhhc1- and Zdhhc2-mediated Gpm6a palmitoylation for the regulation of Procr stability, aMaSC activity, and postnatal mammary development.


Subject(s)
Acyltransferases , Lipoylation , Mammary Glands, Animal , Animals , Acyltransferases/metabolism , Acyltransferases/genetics , Mammary Glands, Animal/metabolism , Mammary Glands, Animal/cytology , Mice , Female , Mice, Knockout , Humans , Membrane Microdomains/metabolism , Stem Cells/metabolism , Stem Cells/cytology , Protein Stability
6.
J Radiat Res ; 65(5): 640-650, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39238338

ABSTRACT

Ionizing radiation promotes mammary carcinogenesis. Induction of DNA double-strand breaks (DSBs) is the initial event after radiation exposure, which can potentially lead to carcinogenesis, but the dynamics of DSB induction and repair are not well understood at the tissue level. In this study, we used female rats, which have been recognized as a useful experimental model for studying radiation effects on the mammary gland. We focused on differences in DSB kinetics among basal cells, luminal progenitor and mature cells in different parts of the mammary duct. 53BP1 foci were used as surrogate markers of DSBs, and 53BP1 foci in each mammary epithelial cell in immunostained tissue sections were counted 1-24 h after irradiation and fitted to an exponential function of time. Basal cells were identified as cytokeratin (CK) 14+ cells, luminal progenitor cells as CK8 + 18low cells and luminal mature cells as CK8 + 18high cells. The number of DSBs per nucleus tended to be higher in luminal cells than basal cells at 1 h post-irradiation. A model analysis indicated that basal cells in terminal end buds (TEBs), which constitute the leading edge of the mammary duct, had significantly fewer initial DSBs than the two types of luminal cells, and there was no significant difference in initial amount among the cell types in the subtending duct. The repair rate did not differ among mammary epithelial cell types or their locations. Thus, luminal progenitor and mature cells are more susceptible to radiation-induced DSBs than are basal cells in TEBs.


Subject(s)
DNA Breaks, Double-Stranded , Mammary Glands, Animal , Stem Cells , Animals , Female , DNA Breaks, Double-Stranded/radiation effects , Mammary Glands, Animal/radiation effects , Mammary Glands, Animal/cytology , Stem Cells/radiation effects , Stem Cells/cytology , Stem Cells/metabolism , Rats , Dose-Response Relationship, Radiation , Rats, Sprague-Dawley , Epithelial Cells/radiation effects , Epithelial Cells/metabolism , Epithelial Cells/cytology
7.
Anticancer Res ; 44(10): 4317-4326, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39348974

ABSTRACT

BACKGROUND/AIM: Methyl gallate (MG), a plant phenolic compound, has known anticancer properties. However, its effects on canine mammary gland tumors (CMTs) are unclear. This study evaluated the impact of MG on cell viability, migration, and apoptosis in two CMT cell lines. MATERIALS AND METHODS: CMT-U27 and CF41.mg cells were used. In vitro experiments included MTT and scratch assays, Annexin-V/propidium iodide double staining, immunocytochemistry, and western blot analyses. An in vivo CMT xenograft mouse model was also used to observe the effects of MG on tumor growth and vasculature. Immunohistochemistry was performed to analyze vessel density and apoptosis in tumor tissues. Cell migration and tube formation assays with canine aortic endothelial cells assessed the anti-angiogenic effects of MG. RESULTS: Data showed a significant decrease in cell viability and migration in both CMT cell lines after 24 h exposure to various MG concentrations. MG treatment induced dose-dependent apoptotic cell death and elevated cleaved caspase-3 expression. In vivo experiments confirmed tumor growth suppression 21 days post-treatment with 40 mg/kg MG. Tumor tissues displayed increased cleaved caspase-3 and reduced vessel density. MG also inhibited cell migration and disrupted tube formation in canine endothelial cells. CONCLUSION: MG has potential as an anticancer drug for CMTs by promoting apoptotic cell death and reducing angiogenesis, highlighting its therapeutic promise.


Subject(s)
Angiogenesis Inhibitors , Apoptosis , Cell Movement , Cell Survival , Gallic Acid , Neovascularization, Pathologic , Xenograft Model Antitumor Assays , Animals , Dogs , Apoptosis/drug effects , Female , Gallic Acid/analogs & derivatives , Gallic Acid/pharmacology , Gallic Acid/therapeutic use , Cell Movement/drug effects , Angiogenesis Inhibitors/pharmacology , Cell Line, Tumor , Mice , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/pathology , Cell Survival/drug effects , Mammary Neoplasms, Animal/drug therapy , Mammary Neoplasms, Animal/pathology , Cell Proliferation/drug effects
8.
J Dairy Sci ; 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39343206

ABSTRACT

Mammary gland development research in dairy cattle has improved tremendously over the years, ranging from palpation to methods such as DNA/RNA sequencing, histological imaging, and medical imaging. Despite these advancements, there is limited evidence relating milk production with early mammary development due to incomplete and conflicting data. Further, data is typically not collected longitudinally in the same animals allowing for repeated measures analysis. Additional research is necessary to better understand development of the mammary gland and its direct relationship with subsequent ability to produce milk. As ultrasound has been shown to be a reliable method of visualizing mammary gland structure and parenchymal composition throughout the different stages of development in dairy cattle, it is possible that ultrasound technology can be used in future research to monitor and visualize longitudinal mammary development in dairy cattle noninvasively, and identify quantitative features indicative of milk production potential without culling. Identification of features indicative of higher milk production potential would not only aid in the selection of replacement heifers, but also has potential applications to human medicine with possible prediction of lactation potential in humans.

9.
J Dairy Sci ; 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39343227

ABSTRACT

Milk lactose content (LC) physiologically decreases with parity order in dairy cows, but also after udder health inflammation(s) and/or in presence of elevated milk SCC in subclinical cases. Therefore, the progressive decrease in milk LC observed along cows' productive life can be attributed to a combination of factors that altogether impair the epithelial integrity, resulting in weaker tight junctions, e.g., physiological aging of epithelium, mechanical epithelial stress due to milking, and experienced clinical or subclinical mastitis. Mastitis is known to affect the udder synthesis ability too, so our intention through this study was to evaluate if there is a cumulative and lasting effect of mammary gland inflammation(s) on milk yield (MY) and LC. For this purpose, we used diagnoses of clinical mastitis and milk data of Austrian Fleckvieh cows to evaluate the effect of cumulative mastitis events on LC and MY. Only mastitis diagnoses recorded by trained veterinarians were used. Finally, we investigated if cumulative mastitis is a heritable trait and whether it is genetically correlated with either LC or MY. Estimates were obtained using univariate and bivariate linear animal models. A significant reduction in LC and MY was observed in cows that suffered from mastitis compared with those that did not experience udder inflammation. The h2 of cumulative mastitis is promising and much greater (0.09) than the h2 of the binary event itself (≤0.03). The genetic correlations between cumulative mastitis with LC and MY were negative, suggesting that cows with a great genetic merit for MY and LC are expected to be more resistant to repeated inflammations and less recidivist. When we used number of lifetime SCC peaks (≥200,000 or 400,000 cells/mL) to calculate cumulative inflammation events, h2 was even higher (up to 0.38), implying that also subclinical mastitis has a relevant negative impact on both LC and MY. Finally, the present study demonstrated how repeated mastitis events can permanently affect the mammary gland epithelial integrity and synthesis ability, and that the number of cumulative mastitis is a promising phenotype to be used in selection index in combination with other indicator traits toward more resistant and resilient mammary glands.

10.
Vet Comp Oncol ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39234805

ABSTRACT

Mammary gland tumours are common neoplasms that affect female dogs and cats. We compared the accuracy of pre-surgical fine-needle aspiration (FNA) and core needle biopsy (CNB) diagnosing feline (n = 64) and canine (n = 83) mammary gland tumours with excisional histopathology as the gold standard for the definitive diagnosis. We also explored the impact of CNB needle sizes (18G and 16G). FNA, 18G CNB and 16G CNB demonstrated similar accuracy regarding the diagnosis of feline mammary tumours, ranging from 90% to 97.7% (p > 0.05). However, these techniques displayed lower diagnostic accuracy for canine mammary gland tumours: 46.7%-50.9% for FNA, 63.3% for 18G CNB and 73.6% for 16G CNB. In conclusion, FNA and CNB can be used optionally as pre-surgical diagnostic methods for feline and canine mammary gland tumours. However, factors that affect diagnostic accuracy, such as species and diagnostic techniques, should be considered.

11.
Anim Nutr ; 18: 272-283, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39281046

ABSTRACT

Lauric acid (LA) has the possibility to improve milk production in dairy cows by improving mammary gland development, however, the mechanism by which it might regulate mammary gland development is unclear. The influence of LA on milk production, nutrient digestibility and the expression of proteins related to mammary gland development in dairy cows were evaluated. Forty primiparous Holstein dairy cows were divided into 4 groups in a randomized block design. Four treatments included the control (0 g/d LA per cow), low-LA (100 g/d LA per cow), medium-LA (200 g/d LA per cow), and high-LA (300 g/d LA per cow). Yields of milk, fat-corrected milk, and energy-corrected milk quadratically increased (P < 0.05), and yield and content of milk fat linearly increased (P < 0.05) with LA supplementation. Percentages of C12:0, C18:1 and C20:1 fatty acids in milk fat linearly increased (P < 0.05), but that of C16:0 fatty acid linearly decreased (P = 0.046). Supplementation of LA led to a linear and quadratical increase (P < 0.05) in digestibility of dry matter, organic matter, neutral detergent fibre and acid detergent fibre, and ruminal total volatile fatty acid concentration but a linear reduction (P = 0.018) in the ratio of acetate to propionate. The enzymatic activities of ruminal pectinase, xylanase, and α-amylase, and populations of total bacteria and anaerobic fungi increased linearly (P < 0.05), while populations of total protozoa and methanogens decreased linearly (P < 0.05) with increased LA addition. Following LA addition, blood glucose, triglyceride, estradiol, prolactin, and insulin-like growth factor 1 concentrations increased linearly (P < 0.05) and albumin and total protein concentrations increased quadratically (P < 0.05). Moreover, addition of 200 g/d LA promoted (P < 0.05) the expression of protein involved in mammary gland development and fatty acids synthesis. These results suggested that LA addition enhanced milk production and fatty acids synthesis by stimulating nutrient digestion, the expression of proteins associated with milk fat synthesis and mammary gland development.

12.
EMBO Mol Med ; 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39179741

ABSTRACT

The human mammary gland represents a highly organized and dynamic tissue, uniquely characterized by postnatal developmental cycles. During pregnancy and lactation, it undergoes extensive hormone-stimulated architectural remodeling, culminating in the formation of specialized structures for milk production to nourish offspring. Moreover, it carries significant health implications, due to the high prevalence of breast cancer. Therefore, gaining insight into the unique biology of the mammary gland can have implications for managing breast cancer and promoting the well-being of both women and infants. Tissue engineering techniques hold promise to narrow the translational gap between existing breast models and clinical outcomes. Here, we provide an overview of the current landscape of breast tissue engineering, outline key requirements, and the challenges to overcome for achieving more predictive human breast models. We propose methods to validate breast function and highlight preclinical applications for improved understanding and targeting of breast cancer. Beyond mammary gland physiology, representative human breast models can offer new insight into stem cell biology and developmental processes that could extend to other organs and clinical contexts.

13.
Article in English | MEDLINE | ID: mdl-39152530

ABSTRACT

The objective was to conduct a systematic review to clarify the effects of l-arginine supplementation in pregnant and lactating sows on plasma hormone levels, milk production and composition, the body condition of sows and piglet performance. In April 2023, an online search and a systematic search were performed in the following databases: Embase, Scopus, SciELO, Web of Science, PubMed and Science Direct. The combinations of keywords used were sow and arginine and lactation; sow and arginine and lactating; sow and arginine and gestation; sow and arginine and gestating; sow and arginine and pregnancy; sow and arginine and reproduction; piglet and arginine; and sow and arginine and mammary gland. In total, 21 scientific articles with original data were selected according to preestablished criteria. Among the 21 articles, seven (33%) reported measurements of some plasma hormones, and among these, six reported an increase in the levels of at least one hormone, namely, estradiol, insulin-like growth factor 1 (IGF-1), insulin, follicle stimulating hormone, growth hormone or prolactin, with l-arginine supplementation. The parameters of milk were evaluated in 11 studies (52%), one reported an increase in protein content, and one reported an increase in IGF-1 content in milk with supplementation of this amino acid. Of the 14 studies that evaluated the performance parameters of piglets, only four reported improvements in some parameters of piglets from sows that received supplementation. Dietary supplementation of arginine for sows in the final third of gestation and/or lactation may alter the plasma levels of some hormones, which may reflect in greater development of the mammary gland tissue and, consequently, promote benefits on the performance of piglets. However, more studies are needed to evaluate the real impact of this amino acid supplementation on the physiology of the sows, in general, and the performance of suckling piglets.

14.
Vet Sci ; 11(8)2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39195789

ABSTRACT

Mastitis is an inflammation of the mammary gland that can be caused by various factors, including biological, chemical, mechanical, or physical. Microbiological culture, DNA techniques, and high-throughput next-generation sequencing have been used to identify mastitis-causing pathogens in various animal species. However, little is known about microbiota and microbiome changes linked to yak milk mastitis. This study aimed to characterize the milk microbiota of healthy and mastitis-infected yaks using full-length 16S rRNA sequencing. The results showed that the bacterial microbiota comprises 7 phyla, 9 classes, 20 orders, 39 families, 59 genera, and 72 species. Proteobacteria and Firmicutes were the predominant microbial communities, with lower abundances of Bacteroidota, Actinobacteriota, Acidobacteriota, and other minor groupings also observed. Proteobacteria dominated the clinical and subclinical mastitis groups (95.36% and 89.32%, respectively), in contrast to the healthy group (60.17%). Conversely, Firmicutes were more common in the healthy group (39.7%) than in the subclinical and clinical mastitis groups (10.49% and 2.92%, respectively). The predominant organisms found in the healthy group were Leuconostoc mesenteroides, Lactococcus piscium, Carnobacterium maltaromaticum, and Lactococcus raffinolactis. Low abundances of Staphylococcus aureus species were found in both subclinical and clinical mastitis groups, with Moraxella osloensis and Psychrobacter cibarius dominating the subclinical mastitis group and Pseudomonas fluorescens dominating the clinical mastitis group. An alpha diversity study revealed that the healthy group had a higher microbial diversity than the clinical and subclinical mastitis groups. According to beta-diversity analysis, the principal coordinate analysis identified that mastitis-infected samples significantly differed from healthy ones. The milk microbiota of healthy yaks is more varied, and specific prominent taxa within various groups can act as marker microorganisms for mastitis risk. The genera Leuconostoc and Lactococcus are promising candidates for creating probiotics.

15.
J Mammary Gland Biol Neoplasia ; 29(1): 16, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39177859

ABSTRACT

Postpartum breast cancer (PPBC) is a unique subset of breast cancer, accounting for nearly half of the women diagnosed during their postpartum years. Mammary gland involution is widely regarded as being a key orchestrator in the initiation and progression of PPBC due to its unique wound-healing inflammatory signature. Here, we provide dialogue suggestive that lactation may also facilitate neoplastic development as a result of sterile inflammation. Immune cells are involved in all stages of postnatal mammary development. It has been proposed that the functions of these immune cells are partially directed by mammary epithelial cells (MECs) and the cytokines they produce. This suggests that a more niche area of exploration aimed at assessing activation of innate immune pathways within MECs could provide insight into immune cell contributions to the developing mammary gland. Immune cell contribution to pubertal development and mammary gland involution has been extensively studied; however, investigations into pregnancy and lactation remain limited. During pregnancy, the mammary gland undergoes dramatic expansion to prepare for lactation. As a result, MECs are susceptible to replicative stress. During lactation, mitochondria are pushed to capacity to fulfill the high energetic demands of producing milk. This replicative and metabolic stress, if unresolved, can elicit activation of innate immune pathways within differentiating MECs. In this review, we broadly discuss postnatal mammary development and current knowledge of immune cell contribution to each developmental stage, while also emphasizing a more unique area of study that will be beneficial in the discovery of novel therapeutic biomarkers of PPBC.


Subject(s)
Lactation , Mammary Glands, Animal , Mammary Glands, Human , Female , Humans , Mammary Glands, Human/growth & development , Mammary Glands, Human/immunology , Mammary Glands, Human/pathology , Animals , Lactation/immunology , Pregnancy , Mammary Glands, Animal/immunology , Mammary Glands, Animal/growth & development , Mammary Glands, Animal/pathology , Breast Neoplasms/immunology , Breast Neoplasms/pathology , Epithelial Cells/immunology , Immunity, Innate
16.
Development ; 151(15)2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39092607

ABSTRACT

Branching morphogenesis is a characteristic feature of many essential organs, such as the lung and kidney, and most glands, and is the net result of two tissue behaviors: branch point initiation and elongation. Each branched organ has a distinct architecture customized to its physiological function, but how patterning occurs in these ramified tubular structures is a fundamental problem of development. Here, we use quantitative 3D morphometrics, time-lapse imaging, manipulation of ex vivo cultured mouse embryonic organs and mice deficient in the planar cell polarity component Vangl2 to address this question in the developing mammary gland. Our results show that the embryonic epithelial trees are highly complex in topology owing to the flexible use of two distinct modes of branch point initiation: lateral branching and tip bifurcation. This non-stereotypy was contrasted by the remarkably constant average branch frequency, indicating a ductal growth invariant, yet stochastic, propensity to branch. The probability of branching was malleable and could be tuned by manipulating the Fgf10 and Tgfß1 pathways. Finally, our in vivo data and ex vivo time-lapse imaging suggest the involvement of tissue rearrangements in mammary branch elongation.


Subject(s)
Mammary Glands, Animal , Morphogenesis , Animals , Mammary Glands, Animal/embryology , Mammary Glands, Animal/growth & development , Mice , Female , Fibroblast Growth Factor 10/metabolism , Fibroblast Growth Factor 10/genetics , Nerve Tissue Proteins/metabolism , Nerve Tissue Proteins/genetics , Transforming Growth Factor beta1/metabolism , Time-Lapse Imaging , Cell Polarity , Embryo, Mammalian/metabolism , Signal Transduction
17.
J Morphol ; 285(9): e21769, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39188032

ABSTRACT

The unitary mammary gland is a synapomorphy of therian mammals and is thought to have evolved from the pilosebaceous organ in the mammalian stem lineage from which the lactogenic patch of monotremes is also derived. One of the key lines of evidence for the homology of the nipple and the lactogenic patch is that marsupials have retained a transient hair associated with developing mammary glands. However, these structures have not been documented since the early 20th-century drawings of Ernst Bresslau. In this study, we examine the developing mammary organs of Monodelphis domestica and document the presence of mammary hairs in 12-week-old females, as well as their absence after 18 weeks of age. Histochemical staining for cystine confirms the structures as keratinized hairs. Milk ducts of both juvenile and adult nipples show a division between KRT18+ luminal epithelium and KRT14+ ACTA2+ myoepithelium. These patterns match those in eutherians and suggest a conserved ductal morphology and mechanism of milk expulsion. Finally, PTHLH, a peptide hormone which promotes homeotic transformation of hairy skin into hairless nipples in the mouse, was detected in the Monodelphis milk duct during the mammary hair stage, suggesting that the mutual exclusivity of "hairless nipple" and "hair" organ identity is derived in eutherian mammals. These results reveal shared characteristics of the M. domestica nipple with both the eutherian nipple and the pilosebaceous organ, consistent with the evolutionary derivation of the mammary gland from an ancestral hair organ via developmental individualization of pilosebaceous and mammary identities.


Subject(s)
Mammary Glands, Animal , Monodelphis , Animals , Female , Monodelphis/anatomy & histology , Mammary Glands, Animal/anatomy & histology , Mammary Glands, Animal/growth & development , Hair/anatomy & histology , Nipples/anatomy & histology , Biological Evolution
18.
Mamm Genome ; 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39215776

ABSTRACT

MicroRNAs (miRNAs) act as key gene expression regulators, influencing intracellular biological and pathological processes. They are of significant interest in animal genetics as potential biomarkers for animal selection and health. This study aimed to unravel the complex miRNA signature involved in mastitis in in vitro cell culture. For this purpose, we constructed a control and treatment model in ovarian mammary epithelial cells to analyze miRNA responses upon Staphylococcus aureus (S. aureus) stimulation. The high-throughput Illumina Small RNA protocol was employed, generating an average of 7.75 million single-end reads per sample, totaling 46.54 million reads. Standard bioinformatics analysis, including cleaning, filtering, miRNA quantification, and differential expression was performed using the miRbase database as a reference for ovine miRNAs. The results indicated differential expression of 63 miRNAs, including 33 up-regulated and 30 down-regulated compared to the control group. Notably, miR-10a, miR-10b, miR-21, and miR-99a displayed a significant differential expression (p ≤ 0.05) associated to signal transduction, transcriptional pathways, diseases of signal transduction by growth factor receptors and second messengers, MAPK signaling pathway, NF-κB pathway, TNFα, Toll Like Receptor 4 (TLR4) cascade, and breast cancer. This study contributes expanding miRNA databases, especially for sheep miRNAs, and identifies potential miRNA candidates for further study in biomarker identification for mastitis resistance and diagnosis.

19.
Bull Exp Biol Med ; 177(3): 374-378, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39138790

ABSTRACT

The subareolar Sappey's plexus was studied using color lymphography and immunohistochemical methods with a panel of antibodies to podoplanin, smooth muscle actin, low molecular weight cytokeratin AE1/AE3, and GATA3 on archival material obtained during radical mastectomies and sectoral resections with lymph node dissection from 86 patients diagnosed with non-special type breast cancer. At the macro- and microscopic levels, the connection between the subareolar lymphatic plexus and the lymphatic system of the breast parenchyma has been demonstrated. In triple negative breast cancer with metastases to the axillary lymph nodes, the involvement of subareolar lymphatic plexus into lymphogenous metastasis to the lymph nodes of the axillary lymphatic collector was shown.


Subject(s)
Axilla , Breast Neoplasms , Lymph Nodes , Lymphatic Metastasis , Lymphatic Vessels , Humans , Female , Lymphatic Metastasis/pathology , Lymphatic Vessels/pathology , Lymph Nodes/pathology , Middle Aged , Breast Neoplasms/pathology , Actins/metabolism , GATA3 Transcription Factor/metabolism , Lymph Node Excision , Adult , Lymphography/methods , Triple Negative Breast Neoplasms/pathology , Aged , Keratins/metabolism , Membrane Glycoproteins
20.
J Am Vet Med Assoc ; 262(10): 1397-1404, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39084242

ABSTRACT

OBJECTIVE: To describe the indications for and surgical technique of mastectomy of mares and to describe the outcome of 10 mares that underwent mastectomy in a retrospective case series. ANIMALS: 10 mares having disease of one or both mammary glands. CLINICAL PRESENTATION: Medical records (1995 to 2022) from 2 university teaching hospitals were searched to identify mares that had undergone unilateral or bilateral mastectomy. Data regarding history, signalment, diagnostic tests, preoperative treatment, surgical procedure, and postoperative management were reviewed. Follow-up information was obtained by interviewing the owners by telephone. RESULTS: One (n = 4 mares) or both mammary glands (6 mares) were excised for the following reasons: chronic bacterial mastitis (4), neoplasia (3), lymphangiectasia (1), pythiosis (1), and lymphoid hamartoma (1). None of the mares experienced intraoperative complications. The surgical site was closed primarily in 2 mares and left unsutured in 8 mares. Both sutured wounds developed a seroma, and 1 dehisced. The owners reported that the surgical wound, whether sutured or unsutured, was healed within 3 months. All mares returned to use for their intended purpose, but 3 mares were euthanized 2 to 4 years after surgery due to progression of disease. One mare drowned 1 year after discharge. CLINICAL RELEVANCE: Mastectomy can be an effective treatment for mares suffering from disease of one or both mammary glands when the mare is refractory to medical treatment.


Subject(s)
Horse Diseases , Mastectomy , Postoperative Complications , Animals , Female , Horses , Horse Diseases/surgery , Retrospective Studies , Mastectomy/veterinary , Postoperative Complications/veterinary , Treatment Outcome , Mammary Neoplasms, Animal/surgery
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