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Department of Animal Sciences
The Robert H. Smith Faculty
of Agricultural, Food & Environment

The Hebrew University of Jerusalem.

Herzl 229, Rehovot 7610001, Israel
Phone: +972-(0)8-9489119;
Fax: +972-(0)8-9465763;
Yael Lewitus, Department's Secretary
e-mail: yaellew@savion.huji.ac.il

Publications

2020
Zaguri, S. ; Bartman, J. ; Avital-Cohen, N. ; Dishon, L. ; Gumulka, M. ; Chaiseha, Y. ; Druyan, S. ; Rozenboim, I. . Targeted Differential Monochromatic Lighting Improves Broiler Breeder Reproductive Performance. POULTRY SCIENCE 2020, 99, 3697-3708.Abstract
Light perception in birds is composed of the retina and extraretinal sites, located in the brain. Previous studies indicate that selective photostimulation of the eye decreased reproductive performance, whereas extraretinal photostimulation increases it. Differential photostimulation of the retina and extraretinal sites is based on the retina's sensitivity to green wavelengths and on the red wavelengths' ability to penetrate body tissues. We previously found that short-day exposure to green light within a long-day exposure to red light increases reproductive activity in female turkeys and broiler breeder hens. Furthermore, in a study conducted recently in our laboratory, we found that blue light repressed expression of green light receptor in the retina, which can further enhance reproduction activity in broiler breeders. Here, we examined the ``brain activate/eye deactivate'' hypothesis on gonadal axis activity and reproductive performance in a broiler breeder flock. Broiler breeder hens and roosters (ROSS 308) were divided into 5 light-treatment groups (controlled rooms with light-emitting diodes [LED] lamps): warm white (control), long-day (14 h) red (630 nm) and short-day (6 h) green (514 nm) (red-green), long-day green and short-day red (green-red), long-day red and short-day blue (456 nm) (red-blue), and long-day blue and short-day red (blue-red). Birds were reared from 20 to 55 wk of age. Eggs were collected daily. Weekly egg production calculated. All eggs were incubated for fertility and hatchability examination. Blood was drawn monthly for plasma analysis. At 35 wk of age (after peak production) and 55 wk of age (end of the experiment), 10 hens from each treatment group were euthanized, and selected tissues and glands were taken for gene expression trials. Providing long-day red light to extraretinal photoreceptors while maintaining retinal photoreceptors on short day with blue or green light significantly improved reproductive activities, manifested by elevated egg production and gonadal axis activity compared with Controls and primary breeder recommendations. Long-day green light reduced reproductive performances. We suggest that targeted photostimulation enhances reproductive and gonadal axis activities in broiler breeders.
Margalit, L. ; Strauss, C. ; Tal, A. ; Schlesinger, S. . Trim24 And Trim33 Play A Role In Epigenetic Silencing Of Retroviruses In Embryonic Stem Cells. VIRUSES-BASEL 2020, 12.Abstract
Embryonic stem cells (ESC) have the ability to epigenetically silence endogenous and exogenous retroviral sequences. Trim28 plays an important role in establishing this silencing, but less is known about the role other Trim proteins play. The Tif1 family is a sub-group of the Trim family, which possess histone binding ability in addition to the distinctive RING domain. Here, we have examined the interaction between three Tif1 family members, namely Trim24, Trim28 and Trim33, and their function in retroviral silencing. We identify a complex formed in ESC, comprised of these three proteins. We further show that when Trim33 is depleted, the complex collapses and silencing efficiency of both endogenous and exogenous sequences is reduced. Similar transcriptional activation takes place when Trim24 is depleted. Analysis of the H3K9me3 chromatin modification showed a decrease in this repressive mark, following both Trim24 and Trim33 depletion. As Trim28 is an identified binding partner of the H3K9 methyltransferase ESET, this further supports the involvement of Trim28 in the complex. The results presented here suggest that a complex of Tif1 family members, each of which possesses different specificity and efficiency, contributes to the silencing of retroviral sequences in ESC.
Roth, Z. . Cooling Is The Predominant Strategy To Alleviate The Effects Of Heat Stress On Dairy Cows. REPRODUCTION IN DOMESTIC ANIMALS 2020.Abstract
Reduced reproductive performance of lactating cows during the summer is associated mainly with intensive genetic selection for high milk production, which places a great load on the thermoregulatory mechanism. In the last decades, a big effort has been made to explore the mechanism by which heat stress compromises fertility. The data gained so far revealed that the effect of thermal stress on the female reproductive tract is multifactorial in nature. Based on this understanding, new strategies to mitigate the effect of heat stress have been developed. The review summarizes some of the physiological responses of the cow to elevated temperature and discusses its limitations to maintain normothermia. The review emphasizes that cooling is the predominant strategy used today to alleviate the effects of heat stress. Findings from the Israel dairy herd indicate that efficient cooling management can improve milk production during the summer to a similar level of the winter, expressed by summer to winter ratio of 0.98. However, cooling as a singular approach cannot eliminate the decline in reproduction. Nonetheless, an efficient cooling system is a prerequisite for any other strategy. The review suggests additional hormonal treatments to improve reproductive performance during the summer. Given the complexity of heat stress effects on reproduction, comprehensive reproductive management during the summer is suggested, that is combining two or more strategies in a programme, might be more beneficial.
Roth, Z. ; Komsky-Elbaz, A. ; Kalo, D. . Effect Of Environmental Contamination On Female And Male Gametes - A Lesson From Bovines. ANIMAL REPRODUCTION 2020, 17.Abstract
Endocrine-disrupting compounds (EDCs) and foodborne contaminants are environmental pollutants that are considered reproductive toxicants due to their deleterious effects on female and male gametes. Among the EDCs, the phthalate plasticizers are of growing concern. In-vivo and in-vitro models indicate that the oocyte is highly sensitive to phthalates. This review summarizes the effects of di(2-ethylhexyl) phthalate and its major metabolite mono(2-ethyhexyl) phthalate (MEHP) on the oocyte. MEHP reduces the proportion of oocytes that fertilize, cleave and develop to the blastocyst stage. This is associated with negative effects on meiotic progression, and disruption of cortical granules, endoplasmic reticulum and mitochondrial reorganization. MEHP alters mitochondrial membrane polarity, increases reactive oxygen species levels and induces alterations in genes associated with oxidative phosphorylation. A carryover effect from the oocyte to the blastocyst is manifested by alterations in the transcriptomic profile of blastocysts developed from MEHP-treated oocytes. Among foodborne contaminants, the pesticide atrazine (ATZ) and the mycotoxin aflatoxin B1 (AFB1) are of high concern. The potential hazards associated with exposure of spermatozoa to these contaminants and their carryover effect to the blastocyst are described. AFB1 and ATZ reduce spermatozoa's viability, as reflected by a high proportion of cells with damaged plasma membrane; induce acrosome reaction, expressed as damage to the acrosomal membrane; and interfere with mitochondrial function, characterized by hyperpolarization of the membrane. ATZ and AFB1-treated spermatozoa show a high proportion of cells with fragmented DNA. Exposure of spermatozoa to AFB1 and ATZ reduces fertilization and cleavage rates, but not that of blastocyst formation. However, fertilization with AFB1- or ATZ-treated spermatozoa impairs transcript expression in the formed blastocysts, implying a carryover effect. Taken together, the review indicates the risk of exposing farm animals to environmental contaminants, and their deleterious effects on female and male gametes and the developing embryo.
Wein, Y. ; Barshira, E. ; Friedman, A. . Increased Serum Levels Of Advanced Glycation End Products Due To Induced Molting In Hen Layers Trigger A Proinflammatory Response By Peripheral Blood Leukocytes. POULTRY SCIENCE 2020, 99, 3452-3462.Abstract
Induced molting (IM), a severe detriment to animal welfare, is still used in the poultry industry in some countries to increase or rejuvenate egg production and is responsible for several physiological perturbations, possibly including reactive oxidative stress, a form of metabolic stress. Because metabolic stress has been shown to induce a proinflammatory response involved in attempts to restore homeostasis, we hypothesized that similar responses followed IM. To confirm this hypothesis, we initially confirmed the establishment of oxidative stress during IM in 75-wk-old layers by demonstrating increased production of advanced glycation end products (AGE). Concomitant with increased oxidative metabolites, cellular stress was demonstrated in peripheral blood leukocytes (PBL) by increased levels of stress gene products (the glucocorticoid receptor, sirtuin-1, and heat shock protein 70 mRNA). Increased expression of stress proteins in PBL was followed by a proinflammatory response as demonstrated by increased levels of proinflammatory gene products (IL-6 and IL-1 beta mRNA); increased expression of these gene products was also demonstrated in direct response to AGE in vitro, thus establishing a direct link between oxidative and cellular stress. To establish a possible pathway for inducing a proinflammatory response by PBL, we showed that AGE increased a time dependent expression of galactin-3, Toll-like receptor-4, and nuclear factor - kappa B, all involved in the proinflammatory activation pathway. In vivo, AGE formed complexes with increased levels of circulating acute phase proteins (lysozyme and transferrin), products of a proinflammatory immune response, thereby demonstrating an effector response to cope with the consequences of oxidative stress. Thus, the harmful consequences of IM for animal welfare are extended here by demonstrating the activation of a resource-demanding proinflammatory response.
Dayan, J. ; Reicher, N. ; Melkman-Zehavi, T. ; Uni, Z. . Incubation Temperature Affects Yolk Utilization Through Changes In Expression Of Yolk Sac Tissue Functional Genes. POULTRY SCIENCE 2020, 99, 6128-6138.Abstract
The yolk sac tissue (YST) is a multifunctional metabolic organ supporting chicken embryonic development. This study examined whether incubation temperatures (ITs) affect YST functions. For this purpose, 300 eggs were assigned to 3 groups and incubated at control IT of 37.8 degrees C, at 1.5 degrees C below, 36.3 degrees C (cold IT), and at 1.5 degrees C above, 39.3 degrees C (hot IT). For each group, 6 embryos' whole body mass and residual yolk (RSY) weights were recorded during incubation, and YST was sampled for both histology and gene expression analysis. YST functionality during incubation was examined by regression analysis, comparing changes in expression patterns of genes involved in lipid uptake and metabolism (LRP2, ApoA1), oligopeptides uptake (PepT1), gluconeogenesis (FBP1), glycogenesis (GYS2), and thyroid hormones regulation (TTR, DIO1, DIO2). Results show that hot and cold ITs affected YST gene expression and yolk utilization. PepT1 expression decreased towards hatch, in both hot and cold ITs, while in the Control IT, it reached a plateau. ApoA1 and DIO2 expression showed a moderate linear fit compared to polynomial fit in the control. GYS2 expression had no change along incubation, while in the control IT, it showed a polynomial fit. Expression of LRP2, FBP1, and DIO1 genes was affected by either cold or hot IT's. TTR expression patterns were similar in all IT groups. The variations in gene expression patterns observed in the 3 ITs can explain the changes in yolk utilization, an important parameter for hatchling quality. While the control IT showed optimal utilization, with an RSY value of 11.12% at the day of hatch, the cold and hot IT groups exhibited lower utilization with an RSY value of 18.18 and 29.99%, respectively. These findings are the first to show that ITs change the expression of key YST genes, leading to variations in yolk utilization by the embryo.
Roth, Z. . Influence Of Heat Stress On Reproduction In Dairy Cows-Physiological And Practical Aspects. JOURNAL OF ANIMAL SCIENCE 2020, 98, S80-S87.
Shterzer, N. ; Rothschild, N. ; Sbehat, Y. ; Stern, E. ; Nazarov, A. ; Mills, E. . Large Overlap Between The Intestinal And Reproductive Tract Microbiomes Of Chickens. FRONTIERS IN MICROBIOLOGY 2020, 11.Abstract
Recent work characterized the chicken reproductive tract (oviduct) microbiome composition and its similarity to the egg and chick microbiomes. However, the origin of the oviduct microbiome has not been addressed yet. Here, we characterized the microbiome composition along the oviduct (infundibulum, magnum, and shell gland) as well as in the gut (jejunum and cecum) of broiler breeders at 37 weeks of age of the Cobb industrial breed. We found that while the microbiome composition along the oviduct is similar, the three sites, jejunum, cecum, and oviduct hold distinct microbiomes. However, there was also a large overlap in the composition of the gut and oviduct microbiomes, with 55 and 53% of amplicon sequence variants (ASVs) representing 96 and 90% of the total abundance in the jejunum and cecum, respectively, shared with the magnum. Furthermore, we identified a strong correlation between the relative abundance of ASVs in the gut and their probability to be found in the oviduct. These results suggest that material from the gut travels the full length of the oviduct. This is possibly the result of chicken physiology which includes the cloaca, a cavity to which both the intestinal and reproductive tracts open into. As the cloaca is common to birds, reptiles, amphibians, most fish, and monotremes, our finding may be relevant to many vertebrates. Importantly, these results indicate that mere presence in, and ascending of the oviduct are not virulence characteristics specific to pathogens, as commonly thought, but are the result of chicken physiology and characterize all gut bacteria. Furthermore, whereas a vertical transmission route from the hen to the chick has been suggested, our work starts laying a mechanistic foundation to this route, by describing the movement of gut bacteria to the oviduct, where they may be enclosed in the developing egg. Last, as our results show that gut material travels the full length of the oviduct, fertilization in poultry occurs in the presence of at least bacterial products if not live bacteria, and therefore food additives, probiotics, and diet possibly have a much more direct effect on reproduction and egg formation than previously considered.
Roth, Z. . Reproductive Physiology And Endocrinology Responses Of Cows Exposed To Environmental Heat Stress- Experiences From The Past And Lessons For The Present. THERIOGENOLOGY 2020, 155, 150-156.Abstract
The effects of environmental heat-stress on production and reproduction in dairy cows have been intensively studied throughout the past few decades. In light of climate changes and global warming, this issue has gained attention worldwide. So far, most of the documentations are related to warmer-climate regions, however, environmental thermal stress has recently been reported in cooler regions, such as Europe. The review attempts to present the experiences from the past years and lessons for the present. The review highlights some of the environmental characterizations and provides some practical approaches to estimate the level of heat load on farms. For instance, the intensity of heat stress can be evaluated by the temperature humidity index (THI). Other environmental parameters, such as the increased number of consecutive hot days or the increased frequency of extremely hot days, can be also used to estimate the level of heat load on farms. Exposure of dairy cows to environmental thermal stress results in multiple behavioral changes, physiological responses and endocrinological alterations, which in sequence, lead to reduced reproductive performance. Multiple in-vitro studies have been performed for better understanding the mechanism by which heat stress impairs reproductive processes. However, the current review focuses mainly on animal reactions and on the limitations of physiological and behavioral responses in main-taining normothermia, without human intervention. The review provides evidence that thermal stress induces alterations in the hypothalamus-pituitary-ovarian axis. For instance, impaired gonadotropin secretion, attenuation of follicular development, reduced steroid production and progesterone concen-tration in the plasma. These were found to be associated with impaired estrus behavior, reduced oocyte developmental competence and embryo survival. Heat stress also has direct and indirect effects on the preimplantation embryo. The review summarizes the thermo-sensitivity of the embryo and the acqui-sition of its thermotolerance through early developmental stages. Understanding the effects of environmentally elevated temperature on the reproductive physiology of lactating cows is extremely important for the development of new strategies in order to mitigate the effects of heat stress on farms. The review also provides various types of management and practical tools, in order to alleviate the effects of thermal stress. It introduces some approaches that have been developed during recent years, ones that have been practically used to alleviate the effect of the environmental heat load and suggested to be implanted. Cooling is the predominant strategy used nowadays in order to alleviate the effects of heat stress. It includes indirect cooling of the environment surrounding the animal, by providing shed and ventilation (with or without water) or direct evaporative cooling of the cow with water and fans. Using an efficient cooling system can improve milk production during the hot season, but it cannot eliminate the decline in reproduction. The review also discusses some additional approaches such as timed artificial insemination, hormonal treatment and embryo transfer, which have already been developed. These are suggested to be examined, adapted and implemented in dairy farms located in new regions that have recently suffered from environmental heat stress. The review also discusses unclear points and open questions some of which might lead new research directions. (C) 2020 Elsevier Inc. All rights reserved.
Rozner, R. ; Vernikov, J. ; Griess-Fishheimer, S. ; Travinsky, T. ; Penn, S. ; Schwartz, B. ; Mesilati-Stahy, R. ; Argov-Argaman, N. ; Shahar, R. ; Monsonego-Ornan, E. . The Role Of Omega-3 Polyunsaturated Fatty Acids From Different Sources In Bone Development. NUTRIENTS 2020, 12.Abstract
N-3 polyunsaturated fatty acids (PUFAs) are essential nutrients that must be obtained from the diet. We have previously showed that endogenous n-3 PUFAs contribute to skeletal development and bone quality in fat-1 mice. Unlike other mammals, these transgenic mice, carry the n-3 desaturase gene and thus can convert n-6 to n-3 PUFAs endogenously. Since this model does not mimic dietary exposure to n-3 PUFAs, diets rich in fish and flaxseed oils were used to further elucidate the role of n-3 PUFAs in bone development. Our investigation reveals that dietary n-3 PUFAs decrease fat accumulation in the liver, lower serum fat levels, and alter fatty acid (FA) content in liver and serum. Bone analyses show that n-3 PUFAs improve mechanical properties, which were measured using a three-point bending test, but exert complex effects on bone structure that vary according to its source. In a micro-CT analysis, we found that the flaxseed oil diet improves trabecular bone micro-architecture, whereas the fish oil diet promotes higher bone mineral density (BMD) with no effect on trabecular bone. The transcriptome characterization of bone by RNA-seq identified regulatory mechanisms of n-3 PUFAs via modulation of the cell cycle and peripheral circadian rhythm genes. These results extend our knowledge and provide insights into the molecular mechanisms of bone remodeling regulation induced by different sources of dietary n-3 PUFAs.
Komsky-Elbaz, A. ; Kalo, D. ; Roth, Z. . Aflatoxin B1-Induced Alteration Of Spermatozoa's Proteomic Profile Is Associated With Alterations In The Transcriptomic Profile Of In-Vitro-Derived Blastocysts. ANIMAL REPRODUCTION SCIENCE 2020, 220.
Komsky-Elbaz, A. ; Kalo, D. ; Roth, Z. . Effect Of Aflatoxin B1 On Bovine Spermatozoa's Proteome And Embryo's Transcriptome. REPRODUCTION 2020, 160, 709-723.Abstract
This study aims to evaluate the deleterious effect of the mycotoxin aflatoxin 81 (AFB1) on bull spermatozoa and the carryver effect on the developing embryo. Proteomic analysis of AFB1-treated spermatozoa revealed differential expression of proteins associated with biological processes and cellular pathways that involved in spermatozoon function, fertilization competence and embryonic development. Therefore, we assume that factors delivered by the spermatozoa, regardless of DNA fragmentation, are also involved. To confirm this hypothesis, we have used the annexin V (AV) kit to separate the spermatozoa into apoptotic (AV+) and non-apoptotic (AV-) subpopulations which were found to correlate with high- and low DNA fragmentation, respectively. Fertilization with AV+ AFB1-treated spermatozoa, resulted in no blastocyst formation, whereas fertilization with AV- spermatozoa resulted in reduced cleavage rate and formation of genetically altered blastocysts (POU5F1 and SOX2). Microarray analysis of blastocysts derived from 10 mu M AFB1-treated spermatozoa revealed differential expression of 345 genes that involved in cellular pathways such as embryo and placenta development, cell cycle, DNA repair and histone modification, and in signaling pathways, especially calcium signaling pathway. This is the first report on deleterious carrying over effects of AFB1 from the bovine spermatozoa to the formed embryo. Our findings suggest that aside from the damage caused by AFB1 to spermatozoa's DNA integrity, additional damage mechanisms are involved.
Shimoni, C. ; Goldstein, M. ; Ribarski-Chorev, I. ; Schauten, I. ; Nir, D. ; Strauss, C. ; Schlesinger, S. . Heat Shock Alters Mesenchymal Stem Cell Identity And Induces Premature Senescence. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 2020, 8.Abstract
Heat stress can have a serious impact on the health of both humans and animals. A major question is how heat stress affects normal development and differentiation at both the cellular and the organism levels. Here we use anin vitroexperimental system to address how heat shock treatment influences the properties of bovine mesenchymal stem cells (MSCs)-multipotent progenitor cells-which are found in most tissues. Because cattle are sensitive to harsh external temperatures, studying the effects of heat shock on MSCs provides a unique platform to address cellular stress in a physiologically relevant model organism. Following isolation and characterization of MSCs from the cow's umbilical cord, heat shock was induced either as a pulse (1 h) or continuously (3 days), and consequent effects on MSCs were characterized. Heat shock induced extensive phenotypic changes in MSCs and dramatically curtailed their capacity to proliferate and differentiate. These changes were associated with a partial arrest in the G1/S or G2/M checkpoints. Furthermore, MSCs lost their ability to resolve the inflammatory response of RAW macrophages in coculture. A possible explanation for this loss of function is the accumulation of reactive oxygen species and malfunction of the mitochondria in the treated cells. Heat shock treatments resulted in stress-induced premature senescence, affecting the MSCs' ability to proliferate properly for many cell passages to follow. Exposure to elevated external temperatures leads to mitochondrial damage and oxidative stress, which in turn conveys critical changes in the proliferation, differentiation, and immunomodulatory phenotype of heat-stressed MSCs. A better understanding of the effect of heat shock on humans and animals may result in important health and economic benefits.
Reicher, N. ; Melkman-Zehavi, T. ; Dayan, J. ; Uni, Z. . It's All About Timing: Early Feeding Promotes Intestinal Maturation By Shifting The Ratios Of Specialized Epithelial Cells In Chicks. FRONTIERS IN PHYSIOLOGY 2020, 11.Abstract
The small intestine (SI) of chicks (Gallus gallus) matures rapidly during the initial post-hatch period and acquires digestive, absorptive, and secretive capabilities. The effects of the timing of first feeding on the quantities and distribution of specialized epithelial cells, which generate and maintain SI morphology and functionality, have not yet been examined. In this study, we identified specialized SI epithelial cell sub-types, including stem, progenitor, proliferating, and differentiated cells within crypts and villi of chicks during the first 10 days post-hatch, by in situ hybridization (ISH), immunofluorescence (IF), and histochemical staining. We then examined their quantities and ratios between day of hatch and d10 in chicks that were fed upon hatch [early feeding (EF)], compared to chicks that were fed 24 h post-hatch [delayed feeding (DF)]. Results showed that EF increased total cell quantities in the crypts and villi at days 1, 3, 7, and 10, compared to DF (p < 0.0001). At d3, EF, in comparison to DF, decreased crypt stem cell proportions (p < 0.0001), increased crypt proliferating (p < 0.01) and differentiated (p < 0.05) cell proportions, and increased villus enterocyte proportions (p < 0.01). By d10, EF increased both the quantities and proportions of villus enterocytes and goblet cells, compared to DF. We conclude that feeding upon hatch, compared to 24 h-delayed feeding, enhanced SI maturation and functionality by increasing the quantities and proportions of proliferating and differentiated cells, thus expanding the digestive, absorptive, and secretive cell populations throughout the initial post-hatch period.
Levavi-Sivan, B. . Memoriam - Professor Zvi Yaron. GENERAL AND COMPARATIVE ENDOCRINOLOGY 2020, 299.
Hadaya, O. ; Bransi-Nicola, R. ; Shalev, Y. ; Azaizeh, H. ; Roth, Z. ; Muklada, H. ; Deutch, T. ; Landau, S. Y. ; Argov-Argaman, N. . Pistacia Lentiscus Extract Enhances Mammary Epithelial Cells' Productivity By Modulating Their Oxidative Status. SCIENTIFIC REPORTS 2020, 10.Abstract
We assessed the potential of phenolic compounds from Pistacia lentiscus (lentisk) to enhance production of milk constituents in bovine mammary epithelial cells (MEC). MEC were exposed to 0 (control), 1 or 10 ppm of polyphenols from lentisk ethanolic extract (PLEE) for 24 h. PLEE were absorbed by the MEC plasma membrane, but also penetrated the cell to accumulate in and around the nucleus. PLEE increased triglyceride content in the cell and its secretion to the medium, and significantly increased intracellular lipid droplet diameter. Compared to control, PLEE increased dose-dependently the lactose synthesis, secretion of whey proteins, and contents of casein. To evaluate mitochondrial activity under pro-oxidant load, MEC were preincubated with PLEE and exposed for 2 h to H2O2. Exposure to H2O2 increased the proportion of cells with impaired mitochondrial membrane potential twofold in controls, but not in PLEE-pre-treated cells. Accordingly, proton leakage was markedly decreased by PLEE, and coupling efficiency between the respiratory chain and ATP production was significantly enhanced. Thus, lentisk polyphenols divert energy to production of milk fat, protein and lactose, with less energy directed to cellular damage control; alternatively, PLEE enables MEC to maintain energy and oxidative status under extreme metabolic rate required for milk production and secretion, and reduces the limitation on energy required to support production.
Argov-Argaman, N. ; Raz, C. ; Roth, Z. . Progesterone Regulation Of Milk Fat Globule Size Is Vldl Dependent. FRONTIERS IN ENDOCRINOLOGY 2020, 11.Abstract
Progesterone plays a pivotal role during mammogenesis and serves as an inhibitor of the secretory activation of mammary cells in the last days of gestation. However, its role during lactogenesis, in particular its involvement in lipid metabolism, and milk fat content and composition, is unknown. Here, we provide new evidence of progesterone's involvement in the regulation of milk fat globule (MFG) synthesis and secretion. Findings from bothin vivoandin vitrostudies indicated that the concentration and the direction (increase vs. decrease) of progesterone concentration to which the mammary epithelial cells (MECs) are exposed affect MFG size. This was found to be very-low-density lipoprotein (VLDL) dependent: in the presence of VLDL, the proportion of MEC with small lipid droplets (<1 mu m) increased 2.4-fold, and the proportion of large lipid droplets (>1 mu m) increased 4-fold; in the absence of VLDL, no differences were found. The findings add to our understanding of the mechanism underlying the regulation of MFG size and provide new evidence for progesterone's role in lipid metabolism in the mammary gland during lactogenesis. The fact that the size, synthesis, and composition of MFG are affected by the cyclic pattern of progesterone concentration in the circulation might have physiologically relevant consequences, in particular on milk as a nutritional source.
Roth, Z. ; Dvir, A. ; Furman, O. ; Lavon, Y. ; Kalo, D. ; Leitner, G. ; Wolfenson, D. . Oocyte Maturation In Plasma Or Follicular Fluid Obtained From Lipopolysaccharide-Treated Cows Disrupts Its Developmental Competence. Theriogenology 2020, 141, 120-127. Publisher's VersionAbstract
Mastitis has deleterious effects on ovarian function and reproductive performance. We studied the association between plasma or follicular fluid (FF) obtained from endotoxin-induced mastitic cows, and oocyte developmental competence. Lactating Holstein cows were synchronized using the Ovsynch protocol. On Day 6 of the synchronized cycle, an additional PGF2α dose was administered, and either Escherichia coli endotoxin (LPS, 10 μg; n = 3 cows) or saline (n = 3 cows) was administered to one udder quarter per cow, 36 h later. Milk samples were collected and rectal temperatures recorded. Cows treated with LPS showed a typical transient increase in body temperature (40.3 °C ± 0.4), whereas cows treated with saline maintained normal body temperature (38.9 °C ± 0.04). A higher (P < 0.05) somatic cell count was recorded for cows treated with LPS. Plasma samples were collected and FF was aspirated from the preovulatory follicles by transvaginal ultrasound probe, 6 h after LPS administration. Radioimmunoassay was performed on plasma samples to determine estradiol and cortisol concentrations. Either FF or plasma was further used as maturation medium. In the first experiment, oocytes were matured in TCM-199 (Control) or in FF aspirated from cows treated with saline (FF-Saline) or LPS (FF-LPS). Cleavage rate to the 2- to 4-cell stage embryo did not differ among groups. However, the proportion of developed blastocysts on Day 7 postfertilization in the FF-LPS group tended to be lower for that in FF-Saline and was lower (P < 0.05) than that in the Control groups (10.6 vs. 22.4 and 24.4%, respectively). In the second experiment, oocytes were matured in TCM-199 (Control), or in plasma obtained from cows treated with saline (Plasma-Saline) or LPS (Plasma-LPS). Similar to the FF findings, cleavage rate did not differ among groups; however, the proportion of developing blastocysts tended to be lower in the Plasma-LPS group than in the Plasma-Saline group and was lower (P < 0.05) from that in the Control group (11.0 vs. 25.5 and 34.7%, respectively). The proportion of apoptotic cells per blastocyst, determined by TUNEL assay, did not differ among the experimental groups. The findings shed light on the mechanism by which mastitis induces a disruption in oocyte developmental competence. Further studies are required to clarify whether the negative effect on oocyte developmental competence is a result of LPS, by itself, or due to elevation of secondary inflammatory agents. © 2019
Burow, S. ; Mizrahi, N. ; Maugars, G. ; von Krogh, K. ; Nourizadeh-Lillabadi, R. ; Hollander-Cohen, L. ; Shpilman, M. ; Atre, I. ; Weltzien, F. - A. ; Levavi-Sivan, B. . Characterization Of Gonadotropin Receptors Fshr And Lhr In Japanese Medaka, Oryzias Latipes. General and Comparative Endocrinology 2020, 285. Publisher's VersionAbstract
Reproduction in vertebrates is controlled by the brain-pituitary-gonad axis, where the two gonadotropins follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh) play vital parts by activating their cognate receptors in the gonads. The main purpose of this work was to study intra- and interspecies ligand promiscuity of teleost gonadotropin receptors, since teleost receptor specificity is unclear, in contrast to mammalian receptors. Receptor activation was investigated by transfecting COS-7 cells with either Fsh receptor (mdFshr, tiFshr) or Lh receptor (mdLhr, tiLhr), and tested for activation by recombinant homologous and heterologous ligands (mdFshβα, mdLhβα, tiFshβα, tiLhβα) from two representative fish orders, Japanese medaka (Oryzias latipes, Beloniformes) and Nile tilapia (Oreochromis niloticus, Cichliformes). Results showed that each gonadotropin preferentially activates its own cognate receptor. Cross-reactivity was detected to some extent as mdFshβα was able to activate the mdLhr, and mdLhβα the mdFshr. Medaka pituitary extract (MPE) stimulated CRE-LUC activity in COS-7 cells expressing mdlhr, but could not stimulate cells expressing mdfshr. Recombinant tiLhβα, tiFshβα and tilapia pituitary extract (TPE) could activate the mdLhr, suggesting cross-species reactivity for mdLhr. Cross-species reactivity was also detected for mdFshr due to activation by tiFshβα, tiLhβα, and TPE, as well as for tiFshr and tiLhr due to stimulation by mdFshβα, mdLhβα, and MPE. Tissue distribution analysis of gene expression revealed that medaka receptors, fshr and lhr, are highly expressed in both ovary and testis. High expression levels were found for lhr also in brain, while fshr was expressed at low levels. Both fshr and lhr mRNA levels increased significantly during testis development. Amino acid sequence alignment and three-dimensional modelling of ligands and receptors highlighted conserved beta sheet domains of both Fsh and Lh between Japanese medaka and Nile tilapia. It also showed a higher structural homology and similarity of transmembrane regions of Lhr between both species, in contrast to Fshr, possibly related to the substitution of the conserved cysteine residue in the transmembrane domain 6 in medaka Fshr with glycine. Taken together, this is the first characterization of medaka Fshr and Lhr using homologous ligands, enabling to better understand teleost hormone-receptor interactions and specificities. The data suggest partial ligand promiscuity and cross-species reactivity between gonadotropins and their receptors in medaka and tilapia. © 2019 The Authors
2019
Davidson, I. ; Altory-Natour, A. ; Haddas, R. ; Nagar, S. ; Meir, R. ; Avital-Cohen, N. ; Rozenboim, I. . Evaluation Of Viral-Induced Stress By Quantitating Corticosterone In Feathers Of Virus-Infected Specific Pathogen-Free Chicks. The Journal of Applied Poultry Research 2019. Publisher's VersionAbstract
Physiological stress is known to promote economic losses by causing immunosuppression. Various factors induce stress, including non-optimal management and infection with various pathogens. The concentration of the stress hormone, corticosterone, is indicative of stress in birds. However, its measurement is difficult due to its elevation caused by catching, handling, bleeding, short half-life in the blood, and short secretion period in feces. We describe a novel method to assess corticosterone concentration by sampling feathers. The viruses studied were 2 immunosuppressive viruses, Marek's disease virus and chicken anemia virus, the respiratory viruses, influenza virus H9N2, Newcastle disease virus, and Infectious bronchitis virus. The study contributes novelty as virus-induced stress by feather examination was described sporadically in chickens previously, and feathers were used to detect corticosterone mainly in dead wild and captive birds. Also, the development of extraction method from feathers is novel by using PBS instead of methanol, and by preparing the feather homogenate with steroid displacement reagent.The study findings revealed that virus infections increased the corticosterone concentrations in feather tips to various extents, from 2× to 10× fold, demonstrating that birds endure stress in addition to the clinical and pathological effects induced by the virus infections.