Source: UNIVERSITY OF KENTUCKY submitted to NRP
SE-FORM CHANGES IN LIPIDS, METABOLITES, AND ANTIOXIDANT CAPACITY IMPROVE BEEF COW FERTILITY
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
ACTIVE
Funding Source
AFRI COMPETITIVE GRANT
Reporting Frequency
Annual
Accession No.
1030167
Grant No.
2023-67012-39788
Cumulative Award Amt.
$220,000.00
Proposal No.
2022-09764
Multistate No.
(N/A)
Project Start Date
May 15, 2023
Project End Date
May 14, 2026
Grant Year
2023
Program Code
[A1211]- Animal Health and Production and Animal Products: Animal Reproduction
Recipient Organization
UNIVERSITY OF KENTUCKY
500 S LIMESTONE 109 KINKEAD HALL
LEXINGTON,KY 40526-0001
Performing Department
(N/A)
Non Technical Summary
In many parts of the United States levels of selenium are deficient in the soils. This translates to deficiencies of this essential trace mineral in the forages that sustain grazing cattle. Producers must therefore supplement selenium to their cattle to alleviate the negative physiological effects of this deficiency. Selenium is normally provided to cattle in an inorganic form; however, organic forms are consumed when cattle naturally graze forage. Previous research has demonstrated that compared to supplementing selenium as a purely inorganic form, providing selenium as a mixed blend composed of 50% inorganic and 50% organic selenium advances the development of the conceptus at maternal recognition of pregnancy, the critical period when the embryo signals to the mother that it is present and preparing to implant within the uterus. This timing is concurrent with changes in metabolites in the blood and transcriptional changes in the endometrium suggesting that the mixed form of selenium is altering available energy and metabolites that support conceptus development. This study will determine the mechanistic connection among forms of selenium, metabolic changes in the liver, and energy availability in the endometrium, operating with the hypothesis that these changes will favorably facilitate an environment stimulating conceptus development and viability. It is expected that the provision of the mixed blend of selenium as a necessary supplement will mitigate the effects of oxidative stress in the liver and endometrium resulting in increased availability of metabolites and lipids for utilization by the endometrium and subsequently, the elongating conceptus. This study will connect the metabolic changes in the liver with the physiological responses in the endometrium when supplementing selenium as a blend of organic and inorganic forms, compared to the industry standard of inorganic selenium alone. Implications of this research are the widespread adoption of a different formulation of supplemental selenium that will improve embryonic growth and overall fertility in cow/calf operations, and hence the productivity and sustainability of the beef industry as a whole.
Animal Health Component
25%
Research Effort Categories
Basic
75%
Applied
25%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
30133101020100%
Knowledge Area
301 - Reproductive Performance of Animals;

Subject Of Investigation
3310 - Beef cattle, live animal;

Field Of Science
1020 - Physiology;
Goals / Objectives
The major goal of this project is to determine how manipulation of the form of selenium (Se) supplemented to cattle grazing pastures grown on Se-deficient soils (a widespread problem in the US) can increase fertility, and hence productivity and sustainability of the beef industry. This study will investigate the cellular and molecular mechanisms by which a novel mixed 50% organic: 50% inorganic-form (MIX) of Se, versus the industry standard inorganic Se (ISe) alone, alters the lipids, metabolites, and antioxidant capabilities that contribute to a larger conceptus size previously observed in MIX-supplemented cattle at maternal recognition of pregnancy (MRP). The objective of this project is to determine the mechanism of how the MIX-form of Se as a necessary mineral supplement will 1) mitigate changes in the liver that affect cell health, redox-function, and production of metabolites, and 2) determine metabolic, lipidomic, and metabolomic changes in intercaruncular and caruncular endometrial tissue that affect cell health, redox-function, and availability of energy sources in the endometrium at MRP.
Project Methods
ApproachWe have collected hepatic tissue from the mid-lower right lobe, and intercaruncular (ICAR) and caruncular (CAR) endometrial tissue samples from heifers on Day 17 of pregnancy (inorganic selenium, ISe: n=6, 50% inorganic: 50% organic selenium, MIX: n=6), as described in (Crites et al., 2022). These samples will be utilized in the present study.Objective 1. Using samples of liver, we will determine Se-form dependent changes that affect cell health, redox-function, and production of metabolites at maternal recognition of pregnancy (MRP). This objective is subdivided into 6 experiments as follows.Experiment 1.1 will quantify hepatic concentrations of cholesterol in samples retrieved from ISe vs MIX-supplemented heifers.Experiment 1.2 will determine the expression of transcripts involved in de novo cholesterol synthesis and lipoprotein receptors in samples retrieved from ISe vs MIX-supplemented heifers.Experiment 1.3 will determine hepatic antioxidant capacity by analyzing the relative abundance of mRNA transcripts for selenoproteins with known or proposed antioxidant capacities in samples retrieved from ISe vs MIX-supplemented heifers.Experiment 1.4 will quantify the total antioxidant status in the liver in fresh biopsies that will be collected on Day 17 of pregnancy in ISe vs MIX-supplemented heifers.Experiment 1.5 will determine the intra-hepatic concentrations of the energy substrates acetate, butyrate, and propionate in samples retrieved from ISe vs MIX-supplemented heifers.Experiment 1.6will quantify the glutamine/ glutamate metabolic potential by first quantifying the relative concentrations of mRNA encoding enzymes and receptors in glutamine/ glutamate metabolism and the production of glutathione in samples retrieved from ISe vs MIX-supplemented heifers.Objective 2. Using samples of endometrium, we will determine Se-form dependent changes that affect cell health, redox-function, and availability of energy sources at MRP. This objective is subdivided into 5 experiments as follows.Experiment 2.1 will quantify differences in the ICAR and CAR endometrial antioxidant capacity by analyzing the relative abundance of mRNA transcripts for selenoproteins with known or proposed antioxidant capacities in ISe vs MIX-supplemented heifers.Experiment 2.2 will determine the concentration of energy substrates in the endometrium similarly to conducted in the liver (above) in ISe vs MIX-supplemented heifers.Experiment 2.3 will quantify the glutamine/ glutamate metabolic potential by quantifying the relative concentrations of mRNA encoding enzymes and receptors in glutamine/ glutamate metabolism and the production of glutathione in CAR and ICAR samples from ISe vs MIX-supplemented heifers.Experiment 2.4 will determine the lipidomic and metabolomic profiles in the endometrium from ISe vs MIX-supplemented heifers.Experiment 2.5 will determine differences in mRNA transcripts for lipoprotein receptors, lipoprotein receptor related proteins and facilitative glucose transporters in endometrial samples from ISe vs MIX-supplemented heifers.

Progress 05/15/24 to 05/14/25

Outputs
Target Audience:Our target audience includes animal producers, the scientific community, and citizens of the region and this nation. Changes/Problems:During this reporting period, multiple challenges have occurred. Firstly, Dr. Carr, the post-doctoral PI, was hired as an assistant faculty at Kentucky State University. In the process of transferring the grant to the new institution, there were major changes in both the federal government and within the USDA that significantly delayed the process. We were then able to do a no-cost extension to provide time to finish remaining objectives, given the 5 months of research capabilities lost during the transition time. We are confident that with the NCE and transferring the grant, objectives will be accomplished and data disseminated as previously outlined in the project. What opportunities for training and professional development has the project provided?PI was able to present data to atarget audience while networking and undergoing career development at the 2024 Society for the Study of Reproduction Annual Meeting. How have the results been disseminated to communities of interest?Results have been disseminated via poster presentation at the 2024Society for the Study of Reproduction Annual Meeting. What do you plan to do during the next reporting period to accomplish the goals?During the remaining time of this grant, efforts will be put into finishing the last major objectives of quantifying short chained fatty acids as well as analyzing redox capacity in fresh tissue. We also need to run lipidomic analysis on caruncular endometrium. Additionally, two poster presentations have already been accepted to the American Society of Animal Science Annual Meeting and one publication is awaiting review. More effort will be focused on finalizing the remaining data and publishing the results.

Impacts
What was accomplished under these goals? All targeted mRNA analyses have been completed and data analyzed. Additionally, lipidomic analyses of the liver and intercaruncular tissue as well as metabolomics of the intercaruncular tissue have been completed and data analyzed.

Publications

  • Type: Other Status: Accepted Year Published: 2024 Citation: Carr SN, Crites BR, Shinde H, and Bridges, PJ. 2024. Transcriptomic analysis reveals effects on oxidative phosphorylation and canonical Wnt signaling by form of selenium in the intercaruncular tissue of beef heifers at maternal recognition of pregnancy. SSR Annual Meeting, Dublin, Ireland, July 15-19, 2024.


Progress 05/15/23 to 05/14/24

Outputs
Target Audience:Our target audience includes animal producers, the scientific community, and citizens of the region and this nation. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?This project has provided the opportunity to investigate new laboratory techniques including protein analyses, metabolomics, and lipidomics. These analyses are currently being conducted. It has also provided the opportunity to gain experience managing a grant including working within the structure of the university and managing the budget. Finally, I have been able to present at multiple conferences, sharing research, networking, and staying informed about current research in reproduction. How have the results been disseminated to communities of interest?The results have been disseminated to the scientific community via a publication, a presentation at SSR and multiple presentations at ASAS Southern section meeting. It has also been presented at an interstate journal club hosted by Virginia Tech University. What do you plan to do during the next reporting period to accomplish the goals?Within this next reporting period, I will be conducting and finalizing all data that addresses the remaining experimental goals originally proposed. This includes lipidomics, metabolomics, protein analyses, and quantification of intra-cellular cholesterol. This will then be disseminated across multiple publications and a presentation at SSR 2024.

Impacts
What was accomplished under these goals? Regarding investigating liver cell health, redox-function, and production of metabolites, I have investigated the relative concentration of mRNA transcripts encoding de novo cholesterol synthesis, hormone metabolism, lipoprotein receptors, selenoproteins, glutamine/ glutamate metabolic potential and those regulating gluconeogenic and glycogen stores. Regarding investigating the endometrium, I have investigated the relative concentration of mRNA transcripts encoding selenoproteins and glutamine/glutamate metabolic potential.

Publications

  • Type: Other Status: Accepted Year Published: 2024 Citation: Stamper EM, Jackson JA, Crites BR, Son K, Carr SN, and Bridges PJ. 2024. Selenium-form effects de novo cholesterol synthesis and catabolism of cholesterol and progesterone in the liver of beef heifers (Abstract 1658493). ASAS Southern Section Meeting, Lexington, KY, January 27-30, 2024.
  • Type: Other Status: Accepted Year Published: 2024 Citation: Jackson JA, Stamper EM, Crites BR, Son K, Carr SN, and Bridges PJ. 2024. Selenium-form effects on hepatic function and selenoprotein mRNAs in the early pregnant heifer (Abstract 1661782). ASAS Southern Section Meeting, Lexington, KY, January 27-30, 2024.
  • Type: Other Status: Accepted Year Published: 2024 Citation: Carr SN, Crites BR, and Bridges, PJ. 2024. Transcriptomic changes in response to form of selenium on the interferon-tau signaling mechanism in the caruncular tissue of beef heifers at maternal recognition of pregnancy (Abstract 1661505). ASAS Southern Section Meeting, Lexington, KY, January 27-30, 2024.
  • Type: Journal Articles Status: Accepted Year Published: 2023 Citation: Carr SN, Crites BR, Shinde H, and Bridges PJ. 2023. Transcriptomic changes in response to form of selenium on the interferon-tau signaling mechanism in the caruncular tissue of beef heifers at maternal recognition of pregnancy. International Journal of Molecular Sciences. 24:17327. DOI: 10.3390/ijms242417327
  • Type: Other Status: Accepted Year Published: 2023 Citation: Carr SN, Crites BR, and Bridges PJ. 2023. Effects of form of selenium on serum metabolites and iodothyronine deiodinases during early gestation in beef heifers (Abstract 228). SSR Annual Meeting, Ottawa, Canada, July 11-14, 2023.