Mammary Gland Weight Research Articles

Hepatic-derived extracellular vesicles in late pregnancy promote mammary gland development by stimulating prolactin receptor-mediated JAK2/STAT5/mTOR signalling

The mammary glands develop rapidly in late pregnancy to prepare adequately for lactation. At this stage the liver is crucial for mammary gland development, and it can achieve distal mammary gland regulation through hepatic factors and hormones. Recently, an increasing number of studies have found that hepatic-derived extracellular vesicles play an essential role in organ-to-organ communication, however, its effect on mammary gland development remains unclear. In this study, we extracted hepatic-derived extracellular vesicles from pregnant (P-hEVs) and non-pregnant mice (NP-hEVs), respectively, and explored their regulatory role on mammary gland development. The results revealed that P-hEVs was able to promote the proliferation and differentiation of HC11 cells. In addition, intraperitoneal injection of P-hEVs into pubertal female mice increased mammary gland weight and promoted mammary gland development. Mechanistically, P-hEVs activated the PI3K/AKT signalling pathway to enhance the proliferation of mammary epithelial cells, and also activated prolactin receptor-mediated JAK2/STAT5/mTOR signalling to promote mammary epithelial cell lactation and the synthesis of milk proteins and milk lipids. Overall, mouse liver during pregnancy can transmit signals to the mammary gland in the form of extracellular vesicles to promote its development and provide for subsequent lactation.

Selenomethionine Promotes Milk Protein and Fat Synthesis and Proliferation of Mammary Epithelial Cells through the GPR37-mTOR-S6K1 Signaling.

Selenomethionine (SeMet) is an important nutrient, but its role in milk synthesis and the GPCR related to SeMet sensing is still largely unknown. Here, we determined the dose-dependent role of SeMet on milk protein and fat synthesis and proliferation of mammary epithelial cells (MECs), and we also uncovered the GPCR-mediating SeMet function. At 24 h postdelivery, lactating mother mice were fed a maintenance diet supplemented with 0, 5, 10, 20, 40, and 80 mg/kg SeMet, and the feeding process lasted for 18 days. The 10 mg/kg group had the best increase in milk production, weight gain of offspring mice, and mammary gland weight and acinar size, whereas a higher concentration of SeMet gradually decreased the weight gain of the offspring mice and showed toxic effects. Transcriptome sequencing was performed to find the differentially expressed genes (DEGs) between the mammary gland tissues of mother mice in the 10 mg/kg SeMet treatment group and the control group. A total of 258 DEGs were screened out, including 82 highly expressed genes including GPR37 and 176 lowly expressed genes. SeMet increased milk protein and fat synthesis in HC11 cells and cell proliferation, mTOR and S6K1 phosphorylation, and expression of GPR37 in a dose-dependent manner. GPR37 knockdown decreased milk protein and fat synthesis in HC11 cells and cell proliferation and blocked SeMet stimulation on mTOR and S6K1 phosphorylation. Taken together, our data demonstrate that SeMet can promote milk protein and fat synthesis and proliferation of MECs and functions through the GPR37-mTOR-S6K1 signaling pathway.

Impact of high-fat diet and exposure to constant light on reproductive competence of female ICR mice.

Obesity and exposure to light at night are prevalent in modern society and associated with changes in physiology and behavior that can affect a female's ability to support offspring growth during pregnancy and lactation. A 2X3 factor study of ICR mice was conducted to determine the effect of diet [control (CON; 10% fat) or high fat (HF; 60% fat)] and exposure to regular 12 h light:dark cycles (LD) or continuous low (L5) or high (L100) lux of light on gestation length, birth litter size, milk composition and litter growth to lactation day 12. HF diet reduced birth litter size, but increased postnatal d 12 litter weight (P<0.05), whereas constant light tended to increase litter weight (P=0.07). Continuous light increased gestation length, altered dam feed intake, increased serum prolactin and increased final dam and mammary gland weight (P<0.05), while decreasing mammary ATP content and milk lactose (P<0.05). Correlation analysis indicated a positive relationship between final litter weight and mammary size, metabolic stores (e.g. maternal fat pad weight), kcal of feed intake, and gestation length (P<0.05). Although CON mice spent more time eating than HF dams, the calorically dense HF diet was related to greater rates of litter growth to peak lactation. Constant light circadian disrupting effects appear to be confounded by a potential long day photoperiod response exemplified by higher circulating levels of prolactin and increased body and mammary weight of females exposed to these conditions. Other model systems may be better to study the interacting effects of obesity and circadian disruption on reproductive competence.

Antimicrobial and Anti-inflammatory Activity of Thespesia populnea Mediated Nanoparticles in Murine Mastitis Model

Background: Bovine mastitis is a common inflammatory disease where bacterial resistance to antibiotics is a major concern in its treatment. Nanoparticles have been known in overcoming difficulties of treatment therapies including multi drug resistant bacterial infections but research on their role in mastitis treatment is limited. Nowadays Green synthesis of nanoparticles is gaining importance to overcome problems associated with chemical synthesis. Therefore, the present study was conducted to evaluate the ameliorative action of Thespesia populnea (T. populnea) mediated synthesized silver and zinc oxide nanoparticles in mastitis induced mice. Methods: A total of 48 mice were divided into six groups: where Group I served as control, groups II to VI were inoculated with Staphylococcus aureus (S. aureus) culture for mastitis induction. After mastitis induction, groups III, IV, V and VI received T. populnea methanolic extract (TPE), T. populnea methanolic extract mediated silver nano particles (TPSN) (»95 nm size), T. populnea methanolic extract mediated ZnO nanoparticles (TPZN) (» 85 nm size) and Ceftriaxone respectively. Whole blood was collected to analyze inflammatory indicators haptoglobin (Hp) and C reactive protein (CRP). The mammary gland weights, bacterial load and changes in tissue samples were studied. Result: The formation of brown colour solution and white crystalline precipitate indicated the formation of TPE mediated silver and zinc oxide nanoparticles respectively. The sizes of these TPSN and TPZN when characterized by SEM, were found to be 95 and 85 nm respectively. The values of mammary gland weight, bacterial load, Hp and CRP were elevated significantly in group II mice when compared to other treatment groups. Histopathological examination of mammary gland revealed bacterial clumps, severe leucocytic infiltration along with congestion and necrotic changes in group II. The ameliorating changes in damaged tissues of the experimental groups remained in the decreasing order of TPSN, ceftriaxone, TPZN and TPE respectively. Therefore, phytogenic nanoparticles can be effectively used to control the mastitis.

Abstract P5-06-11: Secreted frizzled related protein 1: From lobular involution to breast osteoimmunological disorder

Abstract Breast cancer is the leading cause of cancer-related death in women worldwide. Our group previously performed a human transcriptome array on normal tissue, atypical ductal hyperplasia, ductal carcinoma in situ and estrogen receptor-α positive invasive ductal carcinoma. Among the transcripts down-regulated during carcinogenesis: Secreted Frizzled-Related Protein 1 (SFRP1), a Wnt signaling pathway antagonist inversely associated with age-related lobular involution has been identified.Interestingly, SFRP1 expression is higher in presence of hydroxyapatite microcalcifications in non-tumoral breast tissue. SFRP1 is also known to be involved in the increase of bone resorption, notably by downregulating osteoblastic differentiation. This suggests that the lack of SFRP1 could be involved in both osteoblast-like phenotype acquisition and early breast carcinogenesis. Unfortunately, data on the mechanism of microcalcifications formation and their impacts on breast carcinogenesis are still lacking.We hypothesize that loss of SFRP1 is responsible for microcalcifications accumulation and early breast carcinogenesis. Our objectives are:1. To define the impact of microcalcifications on SFRP1 expression in non-tumoral mammary gland and 2. to decipher the causal role of SFRP1 in microcalcifications formation. Organoid culture using freshly purified epithelial cells from nulliparous and multiparous mice mammary glands, in presence or in absence of hydroxyapatite crystals has been performed. Organoids number and phenotype have been studied (aim 1). We also have modulated SFRP1 expression in mammary cell lines by lentiviral transduction and performed proliferation, migration and alizarin assays to assess the tumoral aggressivity and cells abilities to produce calcium deposits in vitro (aim 2). SFRP1 and markers of osteoblastic differentiation (Runt-related transcription factor 2, RUNX2) and bone formation (Alkaline Phosphatase, ALPL; Osteopontin, SPP1; Periostin, POSTN) will also be quantified by quantitative PCR in both mice organoids and human mammary cell lines (aims 1 and 2). 1. The ratio between the mammary gland and body weight obtained from nulliparous mice (n = 12) is significantly lower compared with multiparous mice (n = 12; fold-change = 1.84; p-value &amp;lt; 0.001). Hydroxyapatite crystals induced an increase in the proportion of organoids with lumen and branching compared with the control without hydroxyapatite specifically in organoids obtained from nulliparous mice. Organoid’s size and gene expression profiles are still to be assessed. 2. SFRP1 downregulation in a non-tumoral atypical ductal hyperplasia cell line (MCF10AT1) induced an increase in proliferative and migratory cells abilities. It was also responsible for an increase in estrogen receptor 1 (ESR1) expression, suggesting that SFRP1 is related to luminal carcinogenesis. Results also demonstrate that decreasing SFRP1 in MCF10AT1 induced a profile similar to growth stage in bone tissue, which notably means an increase of expression of the osteoblastic transcription factor RUNX2 and the marker of mineralization SPP1, also involved in lactation-related pink adipose tissue formation. We also observed an increase of POSTN expression, known to be involved in decreased bone mineral density during lactation.SFRP1 upregulation in the invasive luminal A cell line MCF7 reduced cell migration and ESR1 expression. Likewise, it increased MCF7 proliferation compared to control. In addition, it induced an increase of RUNX2 and SPP1 expression, similar to what is reported in matrix mineralization profile in bone. These results support our hypothesis that SFRP1 has a causal role in the acquisition of a malignant phenotype but also in osteoblast-like phenotype in mammary epithelial cells. The cause of SFRP1 downregulation in women remains to be explored. Citation Format: Alisson Clemenceau, Aurélie Lacouture, Juliette Bherer, Audet-Walsh Étienne, Caroline Diorio, Francine Durocher. Secreted frizzled related protein 1: From lobular involution to breast osteoimmunological disorder [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-06-11.

Evaluation of Therapeutic Efficacy of Copper Nanoparticles in Staphylococcus aureus‐Induced Rat Mastitis Model

The current study was devised to develop alternative, nonantibiotic, and economically viable treatments for bovine mastitis. The concentration of 6.25 μg/mL (25 nm) CuNPs was selected as intramammary (IM) treatment in S. aureus‐induced mastitis in rats as this concentration showed a significant zone of inhibition through the in vitro sensitivity test and minimal cell toxicity on fibroblast cell lines. After, this in vivo study was conducted, and rats were divided into four groups of 6 rats each: group I (healthy control/deionized water), group II (disease control), group III (CuNPs), and group IV (gentamicin). Injection of gentamicin IM for 5 days was selected on the basis of an antibiotic sensitivity test. The therapeutic efficacy of CuNPs was assessed on the basis of clinical signs, mammary gland architecture, bacterial load, oxidative stress parameters, and histopathology of mammary glands. The clinical signs of mastitis in group III ameliorated within 3 days of treatment while in group IV clinical signs ameliorated within 4 days of initiation of treatment. On the 5th day after randomization, bacterial load, mammary gland weights, TOS (Total Oxidant Status), and OSI (oxidative stress index) were significantly lower in the CuNPs group compared to the disease control group and commercial antibiotic group. Similarly, TAS of group III was significantly higher compared to that of groups II and IV indicating that CuNPs have better ameliorative efficacy in mastitis. Treatment with IM, CuNPs @ 6.25 μg/mL showed early recovery, reduced bacterial loads, and amelioration of oxidative stress indices henceforth resulting in marked amelioration in histopathological changes compared to rats in group IV. From this study, it may be concluded that CuNPs may provide a potential alternative therapeutic regimen for the treatment of bovine mastitis.

Fraction from Calliandra portoricensis reduces 7, 12 dimethylbenz(a)anthracene-induced mammary tumors in Wistar rats.

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 tumors. Materials and Methods:Female Wistar rats (40) were allotted into five equal groups. Group 1 served as control, group 2 received DMBA (50 mg/kg), groups 3 and 4 received DMBA and were treated with CP at doses of 50 and 100 mg/kg respectively, and the group 5 received DMBA and vincristine (0.5 mg/kg). DMBA was injected intraperitoneally once while vincristine and CP were given twice and thrice per week, respectively. Results:Administration ofDMBA 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. Also, 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 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.

PSI-13 Effects of maternal nutrient restriction and melatonin supplementation on fetal mammary gland vascularity

Abstract The objective was to determine fetal mammary gland vascularity following dietary melatonin supplementation in late pregnant nutrient restricted Brangus heifers carrying female fetuses from two different seasons (spring calving, n = 12; fall calving, n = 13). Heifers were assigned one of four nutritional treatments at day 160 of gestation; adequate fed (ADQ-CON; 100% NRC; n = 6), nutrient restricted (RES-CON; 60% NRC; n = 6), adequate fed with 20 mg of melatonin (ADQ-MEL; n = 6), and nutrient restricted with 20 mg of melatonin (RES-MEL; n = 7). Fetal mammary glands were collected at day 240 of gestation following Cesarean delivery. Mammary gland vascularity was determined via immunofluorescence staining and analyzed via ANOVA. In spring calving heifers, maternal body weight was decreased (P = 0.002) in RES (528±11 kg) vs ADQ (601±11 kg) fed. Fetal body weight, fetal mammary gland weight, and mammary gland vascularity were not different (P &amp;gt; 0.15) among treatments. In fall calving heifers, a nutrition by treatment interaction (P = 0.048) was observed for maternal body weight, which was increased in ADQ-MEL versus all groups. Fetal body weight and fetal mammary gland weight were not different (P &amp;gt; 0.45) among groups. In fall calving, fetal mammary gland capillary number and average size were not different (P &amp;gt; 0.40) among groups. However, a nutrition by treatment interaction was observed for capillary area (P = 0.05), which was increased in RES-MEL versus ADQ-MEL. In addition, a nutrition by treatment interaction was observed for capillary perimeter (P = 0.001), which was increased in RES-MEL versus all groups. Overall, maternal nutrient restriction and melatonin supplementation did not impact fetal mammary gland vascularity in spring calving heifers; however, melatonin supplementation during nutrient restriction in fall calving heifers may increase fetal mammary gland vascularity. In conclusion, seasonal differences and natural melatonin production may influence melatonin-induced changes in fetal development.

Chloroform extract of Calliandra portoricensis inhibits tumourigenic effect of N-methyl-N-nitrosourea and benzo(a)pyrene in breast experimental cancer

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.

Different Protein Sources in the Maternal Diet of the Rat during Gestation and Lactation Affect Milk Composition and Male Offspring Development during Adulthood.

Protein sources in maternal diet are important for mammary gland differentiation and milk protein; however, few studies have examined the metabolic and cellular adaptations of mothers based on protein source diets during pregnancy and lactation, and leptin concentration in offspring. We evaluated metabolic parameters and maternal key organs and milk components in mothers at the end of lactation, who were fed different sources of proteins. In postnatal day 110 and 250, we studied development parameters and leptin in male offspring. Female rats received a Vegetal (V) or Animal (A) diet during pregnancy and lactation. After weaning, male offspring ate V diet until postnatal day 250, which yielded two groups: Vv and Av. Milk dry, protein and fat were analyzed. Maternal metabolic parameters, leptin, and liver, adipose tissue and mammary gland histological analyses were studied. Body weight, food intake and leptin were analyzed in offspring at two ages. Adipose tissue weight and cells size and liver fat, mammary gland apoptosis, weight, milk protein and leptin were higher in A vs V. Maternal liver and milk dry were lower in A vs V. All offspring parameters were higher in Av vs Vv at postnatal day 110; however, at postnatal day 250, leptin was higher in Av vs Vv. Maternal serum and milk leptin had a positive correlation with offspring serum leptin at both ages. Consumption of animal protein-based diets by mothers during developmental periods affects specific maternal organs and changes milk composition during lactation, leading to a hyperleptinemic phenotype in male offsprings.

Feed intake–dependent and –independent effects of heat stress on lactation and mammary gland development

With a growing population, a reliable food supply is increasingly important. Heat stress reduces livestock meat and milk production. Genetic selection of high-producing animals increases endogenous heat production, while climate change increases exogenous heat exposure. Both sources of heat exacerbate the risk of heat-induced depression of production. Rodents are valuable models to understand mechanisms conserved across species. Heat exposure suppresses feed intake across homeothermic species including rodents and production animal species. We assessed the response to early-mid lactation or late-gestation heat exposure on milk production and mammary gland development/function, respectively. Using pair-fed controls we experimentally isolated the feed intake-dependent and -independent effects of heat stress on mammary function and mass. Heat exposure (35°C, relative humidity 50%) decreased daily feed intake. When heat exposure occurred during lactation, hypophagia accounted for approximately 50% of the heat stress-induced hypogalactia. Heat exposure during middle to late gestation suppressed feed intake, which was fully responsible for the lowered mammary gland weight of dams at parturition. However, the impaired mammary gland function in heat-exposed dams measured by metabolic rate and lactogenesis could not be explained by depressed feed consumption. In conclusion, mice recapitulate the depressed milk production and mammary gland development observed in dairy species while providing insight regarding the role of feed intake. This opens the potential to apply genetic, experimental, and pharmacological models unique to mice to identify the mechanism by which heat is limiting animal production.

Dibenzoylmethane altered adipose mass, serum lipid and sex steroid hormone in female mice

Dibenzoylmethane (DBM), a β-diketone structural analogue of curcumin, has been reported to exhibit anti-tumorigenic and chemopreventive activities in mouse mammary tumorigenesis. Our previous study indicated that DBM modulates estrogenic action both in vitro and in vivo. In this report, the potential role of DBM as modulator of lipid metabolism in two mouse models was investigated. Several biomarkers and intermediate metabolites related to lipid consumption were measured. The results indicated that the parametrial fat pad weight, the level of triglyceride in both CD-1 and Senear mice fed with 1% DBM, was remarkably reduced. In addition, the estradiol level, uterus and mammary gland weights were significantly decreased in CD-1 and young Senear mice at 55 days of age (during the estrous phase of estrous cycle). The reduction of both estradiol level and triglyceride in serum would explain the inhibitory effect of DBM on mammary tumorigenesis as a modulator in dietary lipid metabolism.

Intervention with Probiotics and Muscadine Grape Extract Shifts Western Diet-Associated Metabolic, Microbial, and Inflammatory Parameters to Reduce Breast Tumor Growth

Abstract Objectives Western diet consumption (WD) is associated with increased risk and poor prognosis for breast cancer (BC) due to altered inflammation, metabolism, and microbial colonization. This study will determine whether intervention with probiotics (prbx) and muscadine grape extract (MGE) reduces these effects. Methods Female C57Bl/6 mice were placed on either control diet (CD) or WD (45% fat and 25% sugar). Mice were randomized into six groups per diet: diet alone, antibiotics (abx), prbx, MGE, MGE + abx, and MGE + prbx (n = 8). Prbx groups received 1 × 105 CFU of a 10-strain probiotic 3x weekly. MGE (0.1 phenolics/mL) and abx (5 mg/mL streptomycin, 1 mg/mL ampicillin, 1 mg/mL colistin) were administered in drinking water. Body weights were measured, and feces was collected for 16S sequencing. EchoMRI was performed on mice (total body adiposity) and livers at the end of the study (13 weeks). Immunohistochemistry (IHC) was used to compare mammary gland (MG) and visceral adipose (VA) inflammation (CD68 and MCP-1). To determine whether dietary interventions effected breast cancer growth, female C57Bl6 mice consuming either CD or WD, were injected with 2.5 × 105 E0771-luc triple negative breast cancer cells into the R4/5 MG. Tumors progressed to 100 mm3 prior to treatment. Size was monitored with calipers and IVIS for 21 days. Results MGE + prbx administration in WD-fed mice resulted in reduced body weight. All intervention groups displayed reduced VA and MG weight compared to WD-fed mice. Significant intervention-mediated gut microbial alterations included changes in proportional abundance of Bacteroidetes, Lactococcus, Lactobacillus, and Bifidobacterium taxa. Interventions modulated VA and MG inflammatory markers. Dietary intervention with MGE, prbx, and MGE + prbx reduced E0771 tumor growth rate in CD-fed mice, but not in WD-fed mice. Conclusions Our data suggests that MGE + prbx modulates diet-induced metabolic, inflammatory, and microbial factors. Treatment with MGE + prbx reduced tumor growth rate in CD-fed mice, but not WD. WD-fed mice developed aggressive tumors that treatments were unable to attenuate. Further analyzing tumor tissue will determine whether MGE + prbx altered the tumor microenvironment to improve CD-associated BC prognosis. Funding Sources Chronic Disease Research Fund.

Effects of maternal protein restriction during pregnancy and lactation on milk composition and offspring development.

Before weaning, breast milk is the physiological form of neonatal nutrition, providing pups with all nutrient requirements. Maternal low-protein diet (LPD) during pregnancy and lactation induces adverse changes in key maternal organs, which have negative effects on pup development. We studied the effects of maternal LPD on liver weight, mammary gland (MG) cell differentiation, milk composition and production and pup development throughout lactation. We fed rats with control (C) or LPD (R) during pregnancy and lactation. At 7 d early, 14 d mid and 21 d late lactation stages, maternal biochemical parameters, body, liver and MG weights were analysed. MG cell differentiation was analysed by haematoxylin and eosin staining; milk nutrient composition and production were studied; pup body, liver and brain weights, hippocampal arachidonic acid (AA) and DHA were quantified. Results showed lower body and liver weights, minor MG cell differentiation and lower serum insulin and TAG in R compared with C. R milk contained less protein and higher AA at early and mid stages compared with C. R pup milk and fat intake were lower at all stages. R protein intake at early and mid stages and DHA intake at mid and late stages were lower compared with C. In R pups, lower body, liver and brain weights were associated with decreased hippocampal AA and DHA. We conclude that maternal LPD impairs liver and MG function and induces significant changes in maternal milk composition, pup milk intake and organ development.

Effect of feeding level during the prepubertal phase on mammary gland development in female goat kids.

The experiment reported in this research communication aimed to determine the effects of post-weaning feeding level after early weaning on mammary parenchyma development in Alpine goats. Thirty Alpine female goat kids were weaned early (at around 9.8 kg and 32 d of age) and fed different levels of concentrate: Control (C, 730 g DM/d, n = 10), Low (L, 365 g DM/d, n = 10) or High (H, 1090 g DM/d, n = 10) until 235 d of age with ad libitum hay and water. Half of the goat kids were slaughtered before puberty (at around 208 d of age) and half at midgestation (at around 308 d of age and 70 d of gestation) for mammary parenchyma sampling. A histological analysis, Western blot and DNA quantification were performed. Blood samples were taken before puberty and at midgestation to determine plasma levels of IGF-I and prolactin. The mammary gland weights before puberty and at midgestation were positively and significantly associated with concentrate level. However, the organization of the mammary parenchyma and protein expression and quantity of DNA in the parenchyma were similar among the three groups. Before puberty, prolactin and IGF-I concentrations were significantly increased by the feeding level. In conclusion, feeding level after early weaning did not impact mammary parenchyma structure although it modified the weight of the mammary gland. The establishment of the mammary gland was not impacted by rearing management before puberty. Hence, increasing the feeding level during the rearing period could be an interesting way to increase the body development of goats without impairing mammary development whilst having a positive impact on reproductive parameters such as litter weight.

Root bark extract of Calliandra portoricensis (Jacq.) Benth. chemoprevents N-methyl-N-nitrosourea-induced mammary gland toxicity in rats

Ethnopharmacological relevanceCalliandra portoricensis (CP) is a herb widely used in Nigeria for the treatment of breast engorgement. However, the scientific evidence of this use and its mechanisms of action is not clearly understood. Aim of the studyWe assessed the chemopreventive effects of methanol extract of CP on N-methyl-N-nitrosourea (NMU)-induced mammary gland toxicity in rats. Materials and methodsFingerprinting of methanol extract of CP by Gas Chromatography-Mass Spectrometry (GC-MS) was done. Female Wistar rats were assigned into eight groups: Group 1 (control), group 2 received NMU only, groups 3, 4 and 5 received NMU and treated with CP at doses of 100, 200 and 300 mg/kg, respectively. Group 6 received CP (300 mg/kg), group 7 received NMU and vincristine, while group 8 received vincristine. ResultsThe weight-gain by rats decreased in all groups that received NMU. Administration of NMU significantly increased organo-somatic weight of mammary gland by 52%. The NMU increased serum nitric oxide, total bilirubin, mammary myeloperoxidase and lipid peroxidation by 76%, 87%, 130% and 21%, respectively, as well as activities of serum aspartate aminotransferase and lactate dehydrogenase. Also, NMU-treated rats had decreased total sulphydryl, reduced glutathione and catalase. Immunohistochemistry revealed strong expression of estrogen, progesterone and EGFR-2 proteins in NMU-treated rats. Treatment with CP (200 and 300 mg/kg) attenuated NMU-induced inflammation and oxidative stress. ConclusionCP ameliorated NMU-induced toxicity by modulating different cellular targets.

Dam characteristics associated with pre-weaning diarrhea in mink (Neovison vison)

BackgroundPre-weaning diarrhea (PWD) in mink, also known as “sticky kits”, is a frequently occurring syndrome in suckling mink kits on commercial mink farms. Outbreaks of PWD result in weakened kits, increased mortality and reduced growth and welfare as well as considerable economic losses for the farmers. The syndrome is regarded as multifactorial with a complex etiology, and studies have focused on associations with environment, management and dam characteristics. The present study was conducted from May to June 2015 and included 70 dams with mink litters with and without PWD. The aims were to examine associations between PWD and mastitis (bacterial infection and histological signs of inflammation or other lesions in the mammary gland), and to examine associations between PWD and other dam-related characteristics (age, litter size, body mass index, and weight and number of active mammary glands of the dam).ResultsUsing multivariable mixed logistic regression analyses with farm id as a random intercept, we found that the odds for PWD in the litter were significantly higher in 1 year old dams versus > 1 year old (OR = 13.3, CI 2.0–90.2, P = 0.01), higher if litter size observed after birth was > 5 kits versus ≤ 5 kits (OR = 16.5, CI 2.2–123.7, P = 0.01), higher if the number of active mammary glands per kit was ≤ 1.5 versus > 1.5 glands per kit (OR = 6.5, CI 1.2–36.0), P = 0.03), and higher in farms with high prevalence of PWD versus low prevalence (OR = 16.8, CI 2.9–97.6, P = 0.002). There were no significant associations between PWD and bacterial infection, histological signs of inflammation or other lesions of the mammary gland, body mass index or weight of mammary gland per kit.ConclusionPre-weaning diarrhea had a statistically significant association with age of the dam, litter size and the number of active mammary glands per kit. However, PWD was not associated with mastitis, body mass index and weight of mammary gland tissue per kit.

Canine Pseudopregnancy: A Review

Canine pseudopregnancy is a normal physiological syndrome that occurs in female dogs in their diestrual phase of estrous cycle. It simulates the peri and post-whelping signs that includes nesting, increase in weight and enlargement of mammary gland, lactation and mothering behavior on toys, shoes, puppies of other bitches. Decreased levels of progesterone, meanwhile raised levels of prolactin predispose the bitches to pseudopregnancy. It is a self-limiting clinical condition; however, anti-prolactin therapy indicated an overt pseudopregnancy. Predisposed bitches not used for breeding purpose. The permanent solution for prevention of this clinical condition is ovariohysterectomy (OHE). In this article reviewed regarding aetiopathophysiology, clinical signs, diagnosis and treatment of pseudopregnancy. Keyword: Canine, pseudopregnancy, syndrome Cite this Article Thangamani A, Srinivas M, Chandra Prasad B, et al. Canine Pseudopregnancy: A Review. Research & Reviews: Journal of Veterinary Science and Technology. 2018; 7(1): 7–11p.

The CAR agonist TCPOBOP inhibits lipogenesis and promotes fibrosis in the mammary gland of adolescent female mice

Constitutive androstane receptor (CAR) is a nuclear receptor that not only regulates drug-metabolizing enzymes but also influences energy metabolism. TC, 1, 4-bis [2-(3, 5-dichloropyridyloxy)] benzene (TCPOBOP) has been shown to inhibit lipogenesis in the liver and adipose tissues. The mammary gland is mainly composed of fat pads and duct systems in adolescent female mice. Here, activation of CAR by TC reduces the mammary gland weight, blocks lipid accumulation by inhibiting lipogenesis and gluconeogenesis, and accelerates collagen formation and fibrosis in the mammary fat pad of adolescent female mice. This information provides a reference for CAR activation, which may affect mammary gland development in adolescent females.

Pathological changes in experimental intramammary infection with different Staphylococcus species in mice

Introduction:Mastitis is caused by different Staphylococcus species, produce great economic loss to farmers. Present study was conducted to know pathological changes in mice inoculated with Staphylococcus epidermidis, S. chromogenes, S. haemolyticus and S. aureus isolated from bovine milk.Materials and Methods:Mice were inoculated with 50 μl (2x104 cfu organisms) per mammary gland and euthanized at 6, 12, 24, 48, 72 and 96 h. Mammary gland weight, gross and histopathological changes of mammary gland, liver, kidney, spleen, heart, lung and inguinal lymph node were studied.Results:Mammary gland weight and percentage of body weight increased at 6 and 96 h in S. aureus and S. haemolyticus infected mice. Gross changes were observed in mammary gland but not in other organs. Mammary gland revealed gross changes from 24 to 72 h in three Coagulase negative staphylococcal (CNS) species and persisted up to 96 h in S. aureus infected mice. Histopathological changes in mammary glands was severe in S. aureus and moderate in CNS species. S. aureus infected mice revealed severe damage to alveoli and loss of alveolar architecture at 96 h but three CNS species infection was overcome by host factors which was evident by proliferation of alveolar epithelial cells. No histological changes were observed in kidney, spleen, lung, heart and inguinal lymph nodes.Conclusions:S. aureus caused severe mastitis in mice when compared to CNS species. Further, it is first report of mice to study CNS mastitis, and in future it can be used as model for CNS mastitis.