Source: AUBURN UNIVERSITY submitted to NRP
NUTRIGENOMICS APPROACH TO DAMPEN THE NEGATIVE EFFECTS OF ENDOPHYTE-INFECTED TALL FESCUE ON BEEF COW-CALF PAIR PERFORMANCE
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
1019941
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
Jun 7, 2019
Project End Date
May 1, 2021
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
AUBURN UNIVERSITY
108 M. WHITE SMITH HALL
AUBURN,AL 36849
Performing Department
Animal Sciences
Non Technical Summary
The objective of this project is to reduce the negative effects of an endophyte fungus on beef heifer's reproductive efficiency and their offspring's growth efficiency while grazing infected tall fescue. To accomplish our objective we will use a combination of genetic testing and supplementation with a specially developed mineral formulation. The genetic test utilize DNA harvested from hair samples to detect tolerance to grazing endophyte-infected tall fescue. The specially developed mineral supplement will be fortified with a protected vitamin (niacin) known to increase peripheral blood flow. Forty-eight cows will be separated into 2 groups based upon their genetic tolerance to the endophyte. Within each group; 12 dams will receive the mineral mix supplement containing niacin and 12 dams will be maintained on mineral supplement without niacin. Calves born from each animal will be maintained on the same dietary treatments as dam. Liver samples of cow-calf pairs exposed to endophyte-infected tall fescue will be collected for DNA extraction in order to determine gene expression analysis. Genetic and nutritional treatments will be tested in genes related to oxidative stress and immune system (dam) and, muscle growth and early adipose tissue development (offspring). Our hypothesis is that genetically tested infected-tall fescue tolerant beef cow-calf pairs receiving the proposed enriched mineral supplement will be more tolerant to endophyte-infected tall fescue resulting in greater conception rates and offspring's growth performance. Genes impacted by treatments will be used as biomarkers for animal selection. Positive outcomes will encourage cow-calf producers to implement these proposed genetic and nutritional programs.
Animal Health Component
30%
Research Effort Categories
Basic
60%
Applied
30%
Developmental
10%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3053310115020%
3013310102020%
3053310101020%
3033310104040%
Goals / Objectives
1) Determine the level of ergot alkaloid detoxification at the cellular level on the liver of genotyped beef heifers and offspring grazing endophyte-infected tall fescue, after supplementation with a mineral mix enriched with rumen-protected niacin.2) Evaluate the occurrence of any alteration in gene expression at the cellular level related to offspring's growth performance due to treatments applied, using liver and skeletal muscle samples.3) Assess the stacked effect of genetic testing for tolerance to fescue toxicosis, mineral and niacin supplementation on heifer's reproductive performance and offspring's growth performance.
Project Methods
We plan to test the effect of mineral supplementation (Fescue EMT, Cargill, Inc. Wayzata, MN), enriched with rumen-protected niacin (Anevis, QualiTech, Inc., Chaska, Minnesota) on 48 genotyped pregnant Angus × Simmental cows and heifers. Cow/heifer and offspring liver and liver/skeletal muscle samples respectively, will be collected to determine gene expression levels and responses to this supplementation strategy. Hair samples will be collected from a total of 153 Angus × Simmental cows and 53 replacement heifers from Auburn University Black Belt Research Station to test them for fescue toxicity resistance using a genetic test (Agbotanica, Columbia, MO). After receiving the results from the genetic test, 48 pregnant animals will be selected for the study and separated in two groups of 24 animals tolerant to fescue toxicity (Star rating = 4 and 5 stars) and 24 animals susceptible to fescue toxicity (Star rating = 0 to 1 star). Within these two groups, we will randomly selected 12 animals that will receive mineral supplementation enriched with rumen-protected niacin on the diet and 12 animals' control (mineral supplement alone). Furthermore, rumen-protected niacin has the aim to increase serum prolactin levels and decrease vasoconstriction and it is required for liver detoxification of portal blood ammonia to urea and liver metabolism of ketones bodies. Cow/heifers will start to receive the mineral supplementation alone or in combination to rumen-protected niacin, three months before calving.The heifer's reproductive stages analyzed will be the last trimester of gestation, the transition period and lactation. After calving, cow/calf pairs will continue grazing ergot alkaloid-contaminated fescue. During these mentioned stages, important physiological, metabolic, and nutritional changes that can significantly affect profitability occurs; these changes are linked to lactation performance, clinical and subclinical postpartum diseases, and reproductive performance.The 48 cow/heifers of the study will be located at Beef Evaluation Center (Auburn, AL) and they will be constantly exposed to endophyte-infected tall fescue seeds prior to biopsy sampling. Treated and control groups will have an assigned pen. Calan gates will be use to ensure individual dose of the mineral mix enriched or not with rumen-protected niacin. Furthermore, fescue seeds offered to the animals will be tested for concentration of ergovaline alkaloids, to determine the specific levels of ergovaline an animal is exposed to. To maintain control of the total ergovaline concentration offered to the animals, hay other than fescue will be provided.The mineral supplement and rumen-protected niacin will be "top dressed" on individual stalls containing each animal's ration (2 pounds) of a soy hulls and corn gluten feed based supplement (50:50). Offspring will be creep-fed and after weaning (~ 9 months old), they will receive progressive increments of supplemental diet until they reach an intake of 4 pounds per day. In order to ensure a daily dose of 5 oz/head/day of the mineral mix and 0.5 grams of rumen-protected niacin, according to manufacturer recommendations, cow/heifers and offspring will be trained to be fed in Calan gates stalls. This will allow us to use the cow/heifer/offspring as the experimental unit.Phenotype data will be collected during summer months to detect animals that exhibit heat stress related traits. These phenotypic measurements include: body weight, body condition scores (BCS, 9 points scale), respiration rate (breaths/min), rectal temperature (?F), hair shedding score and time spent grazing during the daylight hours. Reproductive traits such as pelvic area, calving ease, number of services to breeding, number of days open and Julian calving date will be recorded.Liver biopsies will be performed in cow/heifers at the beginning of the mineral supplementation period, at the beginning of the calving season, at the end of the calving season and before weaning. Skeletal muscle and liver biopsies will be performed in offspring at weaning and, at 30 and 60 days after weaning. Animal IDs will be recorded so that the same animals are biopsied at each time point to provide repeated measures sampling. On each biopsy day, blood will be collected to determine hormonal and metabolic changes due to genetic and nutritional treatment. Upon arrival to the laboratory, blood samples will be centrifuged at 4C for 15 minutes at 2000 rpm and, serum will be isolated from clotted blood and plasma from anticoagulant-treated tubes. Samples will be aliquoted into two even quantities for long-term storage at -80?C prior to analysis. Serum quantification of metabolic indicators includes concentrations of lactate dehydrogenase (LD), aspartate transaminase (AST), alanine transaminase (ALT) and creatine kinase (CK). These metabolites will be analyzed at the Clinical Pathology Lab (Auburn University Vet School). Furthermore, serum prolactin levels will be tested in all heifers at Dr. Brandebourg's lab (Auburn University - Animal Science department) as means of determining if fescue toxicosis is occurring within an animal. Endocrine effects in steers associated with infected tall fescue include reduced prolactin levels. Plasma samples will be used to measure luteinizing hormone (LH) concentration in heifers using radioimmunoassay (Dr. Goodman's lab - West Virginia University).After finalizing sample collection, mRNA samples will be extracted from liver and skeletal muscle tissue using the TRIzol Reagent protocol for total RNA extraction (Invitrogen, Carlsbad, CA). Genes that are known to be biological candidate genes for heat stress (PRLH, SOD2 and SOD1), toxic fescue tolerance (DRD2), increased Proline (PYCR1) and Serine (PSPH) synthesis, shunting of aminoacid carbons into pyruvate (ALT2), ATP synthesis (NDUFC1, NDUFV2, UCRC, COX4, ATP5D, and ATP5F1), glucocorticoid receptor signaling (NR3C1) and mitochondrial mass (COX4) will be analyzed using RT-qPCR in the liver of heifers. Genes known to be responsible for muscle growth (MTOR, PI3K, S6K, 4EBP1, AKT3) and early adipocyte differentiation (CEBPB, CEBPD), adipogenesis (PPARG, CEBPA, SREBP1) and feed efficiency (TAP2, CAMK2, FOXO1) will be tested in offspring's skeletal muscle. The above mentioned genes to be analyzed on heifer's liver will be tested in offspring's liver as well.Statistical analysis Quantitative PCR data will be analyzed using the MIXED procedure of SAS (SAS 9.4 Institute, Cary, NC, USA). Before statistical analysis, normalized qPCR data (using the geometric mean of 3 housekeeping or internal control genes) will be transformed to fold-change relative to day 0 (i.e., beginning of supplementation with enriched Fescue EMT™). To estimate standard errors at day 0 and prevent biases in statistical analysis, normalized qPCR data will be transformed to obtain a perfect mean of 1.0 at day 0, leaving the proportional difference between the biological replicate. The same proportional change will be calculated at all other time points to obtain a fold-change relative to day 0. Fixed effects in the statistical model for each variable analyzed (i.e., genes, animal performance and blood metabolite) included genetic treatment (T-snip genotyped test), nutritional treatment (enriched Fescue EMT™ and control), and interactions of second and third order. Gene expression data analysis will include a repeated-measures statement with an autoregressive covariate structure. Animal performance and blood metabolites will be also analyzed using the MIXED procedure of SAS. The random effect in all models will be cow/offspring within treatment.

Progress 06/07/19 to 05/01/21

Outputs
Target Audience:Scientific community is the main target audience during the reporting period for this project. Furthermore, beef producers who are intending to acquire new products that might help to mitigate fescue toxicosis are also contemplated as target audience. Efforts are focused on research, extension and outreach of new advanced beef nutriepigenomics technology expected to be considered in the future as a way to decrease the occurence of fescue toxicosis. Changes/Problems:An RNA-sequencing analysis was added to this research project expecting a great amount of information about liver transcriptome response to fescue toxicity. What opportunities for training and professional development has the project provided? Nothing Reported How have the results been disseminated to communities of interest?Preliminary results were presented at the national level in the virtual ASAS conference 2020 and at the Auburn University Graduate Student Symposium 2020. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? During the second year of this study, a positive and a negative control group of offspring were added to the project. These animals received endophyte-free fescue seeds with the addition (or not) of rumen-protected niacin. Dams and offspring' BW, blood samples, and liver samples were obtained on Days 0 and 29. Uterine blood flow was measured using Doppler ultrasound on Days 3, 10, 17, and 23 on pregnant dams at mid-gestation. Fecal samples were collected from dams and offspring for microbiome analysis. Finally, urine samples were collected on Day 29 for ergovaline analysis and they were sent to the University of Missouri. Results: Animal Performance: Tolerant dams that received RPN had a greater decrease in their BW compared with other treatments. Genetic and nutritional treatments did not present an effect on milk production or offspring's BW at birth and weaning. Gene expression: results indicate that mRNA expression of SOD1 in TC was upregulated between Day 0 and Day 29. Furthermore, on Day 29, SOD2 expression in SC was significantly lower (P < 0.01). Therefore, SC group could have a lower equilibrium in the redox balance capacity in hepatocytes due to the lower SOD2 expression at Day 29. Furthermore, genes related to liver detoxification processes (Cytochrome P450) were affected by ergovaline presence in the diet. A research paper is under preparation for these results. Uterine blood flow: T-Snip™ and RPN supplementation did not affect any of the Doppler ultrasound parameters analyzed on Day 3, 10, 17, and 23. We were expecting to have a decrease in blood flow due to the fact that Niacin could potentially counteract the negative effect of fescue toxicosis (i.e., vasoconstriction). A research paper with these results is under review. Blood analysis: Complete blood count analysis was performed at the Auburn University College of Veterinary Medicine Pathology Lab. There was a decrease in blood metabolites concentration in all treatments due to the intake of endophyte-infected tall fescue seeds. Research paper to be submitted by the end of January 2021. Microbiome analysis: fecal samples from pregnant cows were analyzed in Dr. Xu Wang's lab and results denoted a significant increase in Ruminococcaceae bacterium when comparing cows that received and did not receive fescue seeds on their diets. Manuscript in preparation. RNA-seq analysis: liver samples from offspring were submitted to Dr. Xu Wang's lab for RNA extraction and library preparation. RNA-seq results are going to be analyzed during 2021 and several manuscripts are expected from these results. Urine samples: urine samples were submitted to the Veterinary Medical Diagnostic Laboratory (Dr. Xiangwei Du) at the College of Veterinary Medicine at the University of Missouri. Dr. Du is currently developing a protocol for ergovaline analysis using the urine samples from this research study. The P.I. was submitting fescue seeds samples to Dr. Du in order to detect ergot alkaloids levels on them. Although, currently Dr. Du does not have in his lab a protocol to detect ergovaline in urine. A publication is expected with a new method to analyze ergot alkaloids in urine samples, which is not available currently in the United States.

Publications

  • Type: Conference Papers and Presentations Status: Published Year Published: 2020 Citation: Alfaro, G., Muntifering, Russell B.; Rodning, Soren P.; Pacheco, Wilmer; Mois�, Sonia J. "Effects of endophyte-infected tall fescue on performance of genotyped pregnant beef cows performance supplemented with rumen-protected niacin" presented online at ASAS Conference 2020
  • Type: Conference Papers and Presentations Status: Published Year Published: 2020 Citation: Alfaro, G., Muntifering, Russell B.; Rodning, Soren P.; Pacheco, Wilmer; Mois�, Sonia J. "Complete blood count analysis on cattle exposed to fescue toxicity and rumen-protected niacin supplementation" presented at Auburn University Graduate Student Symposium 2020
  • Type: Journal Articles Status: Under Review Year Published: 2020 Citation: Gard Schnuelle, J., Blythe, G., Cole, R., Alfaro, G. F., Muntifering, R., Pacheco, W., Rodning, R. P. and Mois�, S. J. 2020 Doppler ultrasonography for evaluation of uterine blood flow on pregnant, genotyped beef cows consuming endophyte-infected tall fescue seeds supplemented with rumen-protected niacin


Progress 06/07/19 to 09/30/19

Outputs
Target Audience:Scientific community is the main target audience during the reporting period for this project. Furthermore, beef producers who are intending to acquire new products that might help to mitigate fescue toxicosisare also contemplated as target audience. Efforts are focused on research, extension and outreach of new advanced beef nutriepigenomics technology expected to be considered in the future as a way to decrease the occurence of fescue toxicosis. Changes/Problems:We propose at the beginning to use a special mineral mix formulated for animals potentially exposed to fescue fungus. After discussing that probability of a confunding effect between administration of rumen-protected niacin and the mentioned special mineral mix formula, we decided to don't offer this product to the cows. No problems were experience during the first year of this research study. What opportunities for training and professional development has the project provided?Two undergraduate students (Ciembra Rice and Sara del Toro Otero) expressed interest in participating in the second part of this research project. They will submit an application to the Undergraduate Research Fellowship in February 2020. How have the results been disseminated to communities of interest?Preliminary data was presented in the2019 Graduate Student Poster Showcase on Wednesday, October 23, 2019 from 5:00-7:00 pm at the Auburn University Alumni Center. What do you plan to do during the next reporting period to accomplish the goals?In summer semester 2020, we are going to receive the offspring of the cows and heifer that participate in the first year of this study. Samples for the second year will be processed immediately after biopsy days in order to speed up the data generation process. My student Gaston Alfaro and I are already registered in the ASAS-CSAS Annual Meeting & Trade Show conference in Madison, WI that is going to take place in July 19-23, 2020. It is expected that Gaston will present results from year 1 for this fescue study as an oral presentation.

Impacts
What was accomplished under these goals? Ninety days prior to calving, genotyped pregnant Angus ×Simmental cows (n = 11) and heifers (n = 17) were stratified by Body Weight (BW; 540 ±207 kg) and T-Snip™ Genetic Test for Fescue toxicity resistance (Susceptible or Tolerant); and randomly assigned to dietary treatments: 1) Susceptible Control (SC); 2) Susceptible Niacin (SN); 3) Tolerant Control (TC); and 4) Tolerant Niacin (TN). Dams' BW, blood samples, and liver samples were obtained on Days 0 and 29. Uterine blood flow was measured using Doppler ultrasound on Days 3, 10, 17 and 23. Results indicate thatmRNA expression of SOD1 in TC was upregulated between Day 0 and Day 29. •At Day 29, SOD2 expression in SC was significantly lower (P < 0.01). •T-Snip™ and RPN supplementation did not affect Left Resistance Index (LRI)and Right Resistance Index(RRI) at Day 3, 10, 17, and 23 . •There was a treatment × time interaction (P < 0.05), and time effect (P < 0.05) on BW being TN lighter as compared to the other treatment groups. Beef heifer/cows tested to be susceptible to fescue toxicosis using T-Snip™ Genetic Test that did not received rumen-protected niacin could have lower anti-oxidant capacity in hepatocytes due to the lower SOD2 expression at Day 29. Neither RPN administration nor fescue toxicity tolerance have an effect on any parameter on uterine blood flow. We were expecting to have a decrease in blood flow due to the fact that Niacin could potentially counteract the negative effect of fescue toxicosis (i.e., vasoconstriction). Beef heifer/cows tested to be tolerant to fescue toxicosis by T-Snip™ Genetic Test and did receive RPN supplementation had a higher decrease in BW compared with other treatments.

Publications

  • Type: Conference Papers and Presentations Status: Published Year Published: 2019 Citation: Alfaro Gast�n F.; Muntifering, Russell B.; Rodning, Soren P.; Gard, Julie; Cole, Robert; Pacheco, Wilmer; Mois�, Sonia J. "Nutrigenomics approach to dampen the negative effects of endophyte-infected tall fescue on pregnant beef cows performance" presented as a poster in the 2019 Graduate Student Poster Showcase on Wednesday, October 23, 2019 at the Auburn University Alumni Center.