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Mammals are defined by a unique tissue, the mammary glands, which secrete milk that feed their offspring. Even though a milk supply is vital to species’ survival, the molecular mechanisms that regulate lactation remain obscure. Recent research shows that acquiring nutrients from mother’s milk confers a lifetime of benefits, yet many women around the world are unable to produce sufficient milk to supply the needs of their infant. Establishing therapeutically targetable molecules that drive lactation promises to help women experiencing lactation insufficiency syndrome and expand the health of the population. In my thesis work, I show that the protein Van Gogh-like 2 (VANGL2) plays a novel role in the nucleus where it inhibits differentiation of mammary epithelial cells into milk producing alveolar cells. My data show that VANGL2, working in conjunction with the polycomb repressor protein BMI1, represses the transcription of pro-differentiation genes. Decreasing the nuclear localization of VANGL2 results in precocious differentiation and more milk. This research presents a novel role for VANGL2 in regulating gene transcription at a crucial point in tissue differentiation, making it an appealing clinical target for lactation insufficiency.

This study evaluated the feasibility of using different coding systems for categorical variables when using continuous and categorical variables together for the modeling of the lactation milk yield of Awassi sheep. In the study, when all variables were included in the model, and Dummy Coding and Effect Coding methods were used for age, the effects of lactation duration, average daily milk yield, type of birth, and age 5 group were found to be statistically significant in addition to the constant term. When the Deviation Coding method was used for age, the effects of lactation duration and average daily milk yield were found to be statistically significant in addition to the constant term. On the other hand, when Forward and Backward Coding methods were used, the effect of the age 5 group was found to be statistically significant, along with the effects of lactation duration and average daily milk yield. The results of the study indicated that different results can be obtained depending on the various coding systems used. The results also indicated that the choice of coding system affected the interpretation of the obtained coefficients. Therefore, it can be stated that the aims of the researcher in the study should be defined clearly and the proper codding system should be selected according to the variables to be included in the model.

Three COVID-19 vaccines are licensed for emergency use in the USA: the Pfizer/BioNTech and Moderna/NIH mRNA-based vaccines, and the Johnson & Johnson (J&J)/Janssen human adenovirus (Ad26) vaccine. These vaccines have immunized [~]160 million people nationwide, comprising [~]53% Pfizer, 39% Moderna, and 8% J&J recipients [1]. Although at varying stages of clinical investigation for use in children, no COVID-19 vaccines are yet available for this population, posing a significant public health concern. One method to protect infants and young children may be passive immunization via antibodies (Abs) provided in the milk of a lactating vaccinated person. Our early work [2] and other recent reports [3-5] examining the milk Ab response to mRNA-based COVID-19 vaccination have demonstrated that unlike the post-SARS-CoV-2 infection milk Ab profile, which is rich in specific secretory (s)IgA, the vaccine response is highly IgG-dominant. In this report, we present a comparative assessment of the milk Ab response elicited by not only the Pfizer and Moderna vaccines, but importantly, the J&J vaccine as well. This analysis revealed that compared to mRNA vaccine recipients, 49% - 63% fewer J&J vaccine recipient milk samples were positive for Spike-specific IgG, with positive samples exhibiting significantly lower mean IgG titers. J&J recipient milk samples contained significantly less specific IgA than Moderna recipient milk samples, which exhibited significantly greater relative IgA increases compared to both Pfizer and J&J recipients. Absolute and relative vaccine-induced secretory Ab titers were similarly low for all groups, though [~]25% more Moderna recipients exhibited a relative increase compared to Pfizer and J&J recipients. These data indicate that J&J vaccine poorly elicits Spike-specific Ab in milk compared to mRNA-based vaccines and that this vaccine should be considered a last choice for immunizing those intending to elicit a strong Ab response in their milk. These data also suggest that Moderna vaccine elicits a superior, albeit moderate, milk (s)IgA response, and highlight the need to design vaccines with optimal protection of the breastfeeding infant in mind.

The mammary gland is a vital exocrine organ that has evolved in mammals to secrete milk and provide nutrition to ensure the growth and survival of the neonate The mouse mammary gland displays extraordinary plasticity each time the female undergoes pregnancy and lactation, including a sophisticated process of tertiary branching and alveologenesis to form a branched epithelial tree and subsequently milk-producing alveoli. Upon the cessation of lactation, the gland remodels back to a simple ductal architecture via highly regulated involution processes. At the cellular level, the plasticity is characterised by proliferation of mammary cell populations, differentiation and apoptosis, accompanied by major changes in cell function and morphology. The mammary epithelium requires a specific stromal environment to grow, known as the mammary fat pad. Mammary adipocytes are one of the most prominent cell types in the fat pad, but despite their vast proportion in the tissue and their crucial interaction with epithelial cells, their physiology remains largely unknown. Over the past decade, the need to understand the properties and contribution of mammary adipocytes has become more recognised. However, the development of adequate methods and protocols to study this cellular niche is still lagging, partially due to their fragile nature, the difficulty of isolating them, the lack of reliable cell surface markers and the heterogenous environment in this tissue, which differs from other adipocyte depots. Here, we describe a new rapid and simple flow cytometry protocol specifically designed for the analysis and isolation of mouse mammary adipocytes across mammary gland developmental stages.

Aims This study aims to investigate the effect of hydroxy-selenomethionine supplementation on the in vitro rumen fermentation characteristics and microorganisms of Holstein cows. Methods and Results Five fermentation substrates, including control (without selenium supplementation, CON), sodium selenite supplementation (0.3 mg kg−1 DM, SS03), and hydroxy-selenomethionine supplementation (0.3, 0.6 and 0.9 mg kg−1 DM, SM03, SM06 and SM09, respectively) were incubated with rumen fluid in vitro. The results showed that in vitro dry matter disappearance and gas production at 48 h was significantly higher in SM06 than SM03, SS03 and CON; propionate and total volatile fatty acid (VFA) production was higher in SM06 than CON. Moreover, higher species richness of rumen fluid was found in SM06 than others. Higher relative abundance of Prevotella and Prevotellaceae-UCG-003 and lower relative abundance of Ruminococcus-1 were detected in SM06 than CON. Besides, higher relative abundance of Ruminococcaceae_UCG-005 was found in CON than other treatments. Conclusions It is observed that 0.6 mg kg−1 DM hydroxy-selenomethionine supplementation could increase cumulative gas production, propionate, and total VFAs production by altering the relative abundance of Prevotella, Prevotellaceae-UCG-003, Ruminococcaceae_UCG-005 and Ruminococcus-1, so that it can be used as a rumen fermentation regulator in Holstein cows. Significance and Impact of the Study This study provides an optimal addition ratio of hydroxy-selenomethionine on rumen fermentation and bacterial composition via an in vitro test.

Metabolic disorders in early lactation have negative effects on dairy cow health and farm profitability. One method for monitoring the metabolic status of cows is metabolic profiling, which uses associations between the concentrations of several metabolites in serum and the presence of metabolic disorders. In this cross-sectional study, we investigated the use of mid-infrared (MIR) spectroscopy of milk for predicting the concentrations of these metabolites in serum. Between July and October 2017, serum samples were taken from 773 early-lactation Holstein Friesian cows located on 4 farms in the Gippsland region of southeastern Victoria, Australia, on the same day as milk recording. The concentrations in sera of β-hydroxybutyrate (BHB), fatty acids, urea, Ca, Mg, albumin, and globulins were measured by a commercial diagnostic laboratory. Optimal concentration ranges for each of the 7 metabolites were obtained from the literature. Animals were classified as being either affected or unaffected with metabolic disturbances based on these ranges. Milk samples were analyzed by MIR spectroscopy. The relationships between serum metabolite concentrations and MIR spectra were investigated using partial least squares regression. Partial least squares discriminant analyses (PLS-DA) were used to classify animals as being affected or not affected with metabolic disorders. Calibration equations were constructed using data from a randomly selected subset of cows (n = 579). Data from the remaining cows (n = 194) were used for validation. The coefficient of determination (R2) of serum BHB, fatty acids, and urea predictions were 0.48, 0.61, and 0.90, respectively. Predictions of Ca, Mg, albumin, and globulin concentrations were poor (0.06 ≤ R2 ≤ 0.17). The PLS-DA models could predict elevated fatty acid and urea concentrations with an accuracy of approximately 77 and 94%, respectively. A second independent validation data set was assembled in March 2018, comprising blood and milk samples taken from 105 autumn-calving cows of various breeds. The accuracies of BHB and fatty acid predictions were similar to those obtained using the first validation data set. The PLS-DA results were difficult to interpret due to the low prevalence of metabolic disorders in the data set. Our results demonstrate that MIR spectroscopy of milk shows promise for predicting the concentration of BHB, fatty acids, and urea in serum; however, more data are needed to improve prediction accuracies.

Dietary protein allowances comprise the upper limits of the range of individual metabolic demands adjusted for digestibility and biological value. The maintenance demand includes well defined obligatory and less understood adaptive components. Demands for growth, pregnancy, and lactation are well understood, although factorial models of protein requirements assume low efficiency of dietary protein utilization and may overestimate dietary allowances for children, pregnant, and lactating women. The amino acid profile of the maintenance component is poorly defined but contains fewer indispensable amino acids than that for growth (the tissue protein pattern). Thus protein quality is less important for humans than growing animals.

Feed efficiency and energy balance are important traits underpinning profitability and environmental sustainability in animal production. They are complex traits, and our understanding of their underlying biology is currently limited. One measure of feed efficiency is residual feed intake (RFI), which is the difference between actual and predicted intake. Variation in RFI among individuals is attributable to the metabolic efficiency of energy utilization. High RFI (H_RFI) animals require more energy per unit of weight gain or milk produced compared with low RFI (L_RFI) animals. Energy balance (EB) is a closely related trait calculated very similarly to RFI. Cellular energy metabolism in mitochondria involves mitochondrial protein (MiP) encoded by both nuclear (NuMiP) and mitochondrial (MtMiP) genomes. We hypothesized that MiP genes are differentially expressed (DE) between H_RFI and L_RFI animal groups and similarly between negative and positive EB groups. Our study aimed to characterize MiP gene expression in white blood cells of H_RFI and L_RFI cows using RNA sequencing to identify genes and biological pathways associated with feed efficiency in dairy cattle. We used the top and bottom 14 cows ranked for RFI and EB out of 109 animals as H_RFI and L_RFI, and positive and negative EB groups, respectively. The gene expression counts across all nuclear and mitochondrial genes for animals in each group were used for differential gene expression analyses, weighted gene correlation network analysis, functional enrichment, and identification of hub genes. Out of 244 DE genes between RFI groups, 38 were MiP genes. The DE genes were enriched for the oxidative phosphorylation (OXPHOS) and ribosome pathways. The DE MiP genes were underexpressed in L_RFI (and negative EB) compared with the H_RFI (and positive EB) groups, suggestive of reduced mitochondrial activity in the L_RFI group. None of the MtMiP genes were among the DE MiP genes between the groups, which suggests a non-rate limiting role of MtMiP genes in feed efficiency and warrants further investigation. The role of MiP, particularly the NuMiP and OXPHOS pathways in RFI, was also supported by our gene correlation network analysis and the hub gene identification. We validated the findings in an independent data set. Overall, our study suggested that differences in feed efficiency in dairy cows may be linked to differences in cellular energy demand. This study broadens our knowledge of the biology of feed efficiency in dairy cattle.

We hypothesised that heifers and cows with positive genetic merit for fertility would have a follicular microenvironment that resulted in better quality oocytes. To test this, we compared cumulus cell-oocyte complexes (COC) and follicular fluid from preovulatory follicles of 36 Holstein-Friesian nulliparous heifers and 50 primiparous lactating cows with either positive (POS, +5%) or negative (NEG, −5%) fertility breeding values (FertBV). Established gene markers of oocyte quality were measured in individual cumulus cell masses and oocytes, and concentrations of amino acids, steroids, and metabolites were quantified in corresponding follicular fluid and plasma. The timing of visually detectable oestrus in NEG FertBV heifers was inconsistent with their stage of COC maturation. Retrospective analyses of oestrous activity data indicated that NEG FertBV heifers were sampled earlier. Their recovered COC were morphologically less mature and exhibited differential expression of genes that are associated with follicular maturation (lower levels of BMPR2) and protein processing (higher levels of HSP90B1). Despite consistent sampling times being achieved in the lactating cows, lower concentrations of serine, proline, methionine, isoleucine, and non-esterified fatty acids were present in follicular fluid from POS FertBV cows. This was associated with higher expression of gene biomarkers of good oocyte quality (VCAN, PDE8A) in COC recovered from POS FertBV cows. This study supports our hypothesis that the follicular microenvironment in lactating dairy cows with high genetic merit leads to COC with higher metabolic rates and oocytes of superior quality. Moreover, an additional stressor such as lactation is required for this difference to be pronounced.

The aim of this study was to investigate the effects of some environmental factors like calving year, season, buffalo cow age and village on some milk yield traits of Anatolian buffaloes, such as daily milk yield for lactation length (MYLL), total lactation milk yield (TLMY), lactation length (LL), and daily milk yield for calving interval (MYCI). 1838 milk yield records obtained from 851 Anatolian buffaloes reared under different environmental conditions from 2015 through 2019 within the scope of the Bartın Anatolian Buffalo Breeding Project were assessed. The least square means and standard errors for MYLL, TLMY, LL, and MYCI were 4.07  0.02 kg, 1078.6  7.54 kg, 263.83  1.16 days, and 2.75  0.03 kg, respectively. As a result of the study, the effects of village, calving year and age (P

This study was performed to evaluate the effects of pre-treating a barley-silage-based diet with an exogenous fibrolytic enzyme derived from Trichoderma reesei (FETR, a mixture of xylanase and cellulase) on lactation performance, omasal nutrient flow and digestibility, rumen fermentation characteristics, and rumen pH profile in Holstein dairy cows during early lactation. The dairy trial was conducted using nine Holstein dairy cows (averaging 46 ± 24 days in milk and 697 ± 69 kg body weight, six cows were fitted with a rumen cannula, and three were non-cannulated). Two groups of cows were randomly assigned to each of the dietary treatments in a crossover design: control (without FETR supplementation) and supplemented [with 0.75 mL of FETR·kg−1 dry matter (DM) of the diet based on our previous study]. The application of FETR tended to decrease the DM intake compared with control. There were no effects of FETR (P > 0. 10) on omasal nutrient flow and digestibility, rumen fermentation characteristics, and rumen pH profile. In conclusion, this study lacks evidence that the fibrolytic enzyme (at a level of 0.75 mL of FETR·kg−1 DM) can affect nutrient digestibility, ruminal fermentation, and the performance of early-lactation cows. Further study with larger animal trials are needed.

Objective: This study was conducted to estimate multi-trait genetic parameters for somatic cell score (SCS), milk yield and type traits in Nigerian Dwarf (ND) goats from the United States.Methods: Data from 1,041 ND goats in the United States with kiddings in 95 herds were used to estimate multi-trait genetic parameters for SCS, milk (MILK), fat (FAT), and protein (PROT) yields, and 14 type traits. An 18-trait mixed linear animal model for lactation mean SCS (Log2), MILK, FAT, PROT, and 14 type traits was applied. A factor analytic approach (FA1) in ASReml software was used to obtain convergence.Results: Averages for SCS were low (2.85±1.29 Log2), and were 314±110.6, 20.9±7.4, and 14±4.9 kg, respectively, for MILK, FAT, and PROT. Heritabilities for SCS, MILK, FAT, and PROT were 0.32, 0.16, 0.16, and 0.10, respectively. The highest heritabilities for type traits were for stature (0.72), teat diameter (0.49), and rump width (0.48), and the lowest estimates were for dairyness (0.003) and medial suspensory ligament (0.03). Genetic correlations of SCS with MILK, FAT, and PROT were positive but low (0.25, 0.18, and 0.23, respectively). Genetic and phenotypic correlations between MILK, FAT, and PROT were high and positive (≥0.66). Absolute values of genetic correlations involving SCS with type traits were generally low or no different from zero. Most of the phenotypic correlations involving SCS with type traits were low. No serious unfavorable genetic correlations between milk yield traits and SCS or between milk yield traits or SCS and type traits were found.Conclusion: Genetic variation exists in the ND breed for most studied traits. The development of selection programs based on these estimates may help accelerate favorable multitrait genetic changes in this breed.

The objective of this observational study was to evaluate the association of management-related factors in dry cows and colostrum quantity and quality in Holstein cows on a large commercial dairy farm. This study was conducted from January 2018 to December 2020 on a commercial dairy farm in Germany, milking approximately 2,500 Holstein cows. Dairy personnel recorded colostrum quantity (n = 7,567) and evaluated colostrum quality in a subsample of animals (n = 2,600) using a digital Brix refractometer. Generalized linear mixed models were constructed to evaluate the association of management-related factors and colostrum quantity and quality. Models were run separately for primiparous or multiparous cows. The outcome variable was either colostrum quantity (kg) or quality (% Brix). Average colostrum quantity was 4.0 �� 2.5 kg, 5.1 �� 3.4 kg, and 5.5 �� 3.5 kg for cows in lactation 1, 2, and ���3, respectively. In primiparous cows (n = 2,351), colostrum quantity was affected by month of calving (greatest in April = 4.1 kg, and lowest in November = 3.2 kg), sex of the calf (female singleton = 3.50 �� 0.26 kg; male singleton = 3.76 �� 0.27 kg; twins = 2.97 �� 0.66 kg), stillbirth (stillbirth = 3.14 �� 0.39 kg; no stillbirth = 3.68 �� 0.31 kg). In multiparous cows (n = 5,216), colostrum quantity was affected by month of calving (greatest in May = 5.5 kg, and lowest in October = 3.8 kg), calving ease (calving ease 0 = 4.23 �� 0.26 kg; score 1 = 4.77 �� 0.21 kg; score 2 = 4.98 �� 0.22 kg; score 3 = 5.30 �� 0.22 kg), sex of the calf (female singleton = 4.42 �� 0.21 kg; male singleton = 5.00 �� 0.21 kg; twins = 5.03 �� 0.30 kg), stillbirth (stillbirth = 4.24 �� 0.38 kg; no stillbirth = 5.39 �� 0.11 kg), milk yield in previous lactation (+0.1 kg increase for 1,000 kg more milk yield in previous lactation), days spent in the far-off group (0.05 �� 0.003 kg for every day), and days in the close-up pen (0.06 �� 0.010 kg for every day). Average colostrum quality was 25.1 �� 3.4% Brix, 24.7 �� 3.3% Brix, and 27.6 �� 4.4% Brix for cows in lactation 1, 2, and ���3, respectively. In primiparous cows (n = 817), colostrum quality was affected only by month of calving. Colostrum quality in primiparous cows was greatest in December (26.8% Brix) and lowest in August (23.9% Brix). In multiparous cows (n = 1,783), colostrum quality was affected by parity (lactation 2 = 25.2 �� 2.7% Brix; lactation 3+ = 27.9 �� 2.7% Brix), month of calving (greatest in February = 27.5% Brix, and lowest in August = 25.7% Brix), milk yield in previous lactation, and colostrum quantity. We observed a seasonal pattern for colostrum quantity and quality. Future intervention studies using multiple farms need to elucidate whether management of the photoperiod or length of exposure to close-up diets, or both, can help to optimize colostrum production.

Due to the diversity and limitation of determination methods, published data on the fatty acid (FA) compositions of different milk samples have contributed to inaccurate comparisons. In this study, we developed a high-throughput gas chromatography-mass spectrometry method to determinate milk FA, and the proposed method had satisfactory linearity, sensitivity, accuracy, and precision. We also analyzed the FA compositions of 237 milk samples from Holstein cows, Jersey cows, buffalos, yaks, humans, goats, donkeys, and camels. Holstein, Jersey, goat, and buffalo milks contained high content of even-chain saturated FA, whereas goat milk had higher content of medium- and short-chain FA (MSCFA). Yak and camel milk are potential functional foods due to their high levels of odd- and branched-chain FA and low ratios of n-6 to n-3 polyunsaturated FA (PUFA). Human milk contained lower levels of saturated FA, MSCFA, and conjugated linoleic acid, and higher levels of monounsaturated FA and PUFA. As a special nonruminant milk, donkey milk contained low levels of monounsaturated FA and high levels of PUFA and MSCFA. Based on the FA profiles of 8 types of milk, nonruminant milk was distinct from ruminant milk, whereas camel and yak milk were different from other ruminant milks and considered as potential functional foods for balanced human diet.

Historically, female domestic goats carrying multiple kids are mostly unable to express sufficient nursing ability due to a limited number of functional teats. Therefore, the functional teat is an important component in prolific goat breeding, and plays a key role in the future health of their kids. With this motivation, we wanted to investigate the phenotypic features, litter size, histology of adult female mammary glands, and the gene expression profile of the fibroblast growth factor 2 (FGF-2) gene in goats. To illustrate this, the initial dataset of the current study consists of an electronic questionnaire that includes 697 individuals (548 does and 149 bucks) of five endemic and three exotic goats from 2015 to 2020 in different geographic areas of Iran, from 59 Markhoz (MARG), 50 Azari (AZAR), 73 Busheri (BUSH), 69 Sarbisheh (SARB), 165 Mahabadi (MOHA) indigenous goats and also exotic breeds, including 183 Saanen (SANN), 39 Alpine (ALPN), and 59 Boer (BORE) goats. The results of this study confirmed that MOHA goats (4.16%), BORE (4.43%) and SANN goat breeds (5.75%) have larger litter sizes. Interestingly, the evidence gathering when SNTs occurred showed that both the BUSH and BORE goat breeds had the highest frequency of SNTs. Moreover, under the same physiological and lactation conditions, there was no statistically significant difference in histological features between the three compared does class consist of the two teats, SNTs, and four functional teats. In addition, the results of the gene expression profile significantly highlight the FGF-2 gene pattern in two teat groups compared to other SNT groups (P 0.01). In summary, this scenario can be used to generate further research and facts on responsible candidate genes, the variations in teat numbers in goats, examining both the incidence of SNT and litter size.