A High Protein Model Alters the Endometrial Transcriptome of Mares.
Abstract: High blood urea nitrogen (BUN) decreases fertility of several mammals; however, the mechanisms have not been investigated in mares. We developed an experimental model to elevate BUN, with urea and control treatments (7 mares/treatment), in a crossover design. Urea-treatment consisted of a loading dose of urea (0.03 g/kg of body weight (BW)) and urea injections over 6 hours (0.03 g/kg of BW/h). Control mares received the same volume of saline solution. Blood samples were collected to measure BUN. Uterine and vaginal pH were evaluated after the last intravenous infusion, then endometrial biopsies were collected for RNA-sequencing with a HiSeq 4000. Cuffdiff (2.2.1) was used to identify the differentially expressed genes (DEG) between urea and control groups (false discovery rate-adjusted p-value < 0.1). There was a significant increase in BUN and a decrease of uterine pH in the urea group compared to the control group. A total of 193 genes were DEG between the urea and control groups, with five genes identified as upstream regulators (ETV4, EGF, EHF, IRS2, and SGK1). The DEG were predicted to be related to cell pH, ion homeostasis, changes in epithelial tissue, and solute carriers. Changes in gene expression reveal alterations in endometrial function that could be associated with adverse effects on fertility of mares.
Publication Date: 2019-07-30 PubMed ID: 31366166PubMed Central: PMC6723232DOI: 10.3390/genes10080576Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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The study explores the impact of high blood urea nitrogen (BUN) on the fertility of mares, noting that higher levels of BUN alter the endometrial transcriptome—which could negatively affect fertility.
Research Methodology
- The researchers developed an experimental model to elevate BUN levels in mares. This was accomplished through the administration of a loading dose of urea based on body weight, followed by urea injections over a 6-hour timeframe.
- The study was set up in a crossover design, using two sets of mares (7 mares per group). One group was given urea (the urea-treatment group) and the other a saline solution (the control group).
- Data was then collected from the test subjects. This included blood samples to measure BUN, evaluations of uterine and vaginal pH after the final urea or saline infusion, and endometrial biopsies for RNA-sequencing.
Findings and Analysis
- There was a significant increase in BUN and a decrease in uterine pH for the urea group compared to the control group.
- RNA-sequencing detected differences in gene expression between the two groups. Specifically, 193 genes were differently expressed (DEG), with ETV4, EGF, EHF, IRS2, and SGK1 identified as upstream regulators.
- The DEGs were related to several cellular processes including cell pH regulation, ion homeostasis, changes in epithelial tissue, and solute carriers, suggesting that increased BUN significantly alters the endometrial transcriptome.
Implications
- These changes in gene expression indicate that high BUN levels in mares could cause alterations in endometrial function, possibly leading to decreased fertility.
- This research increases our understanding of BUN’s role in fertility and could guide further studies into improving animal and possibly human fertility.
- The study’s model may provide a basis for future research into the impacts of other physiological or environmental factors on fertility.
Cite This Article
APA
Boakari YL, Ali HE, Dini P, Loux S, Fernandes CB, Scoggin K, Esteller-Vico A, Lawrence L, Ball B.
(2019).
A High Protein Model Alters the Endometrial Transcriptome of Mares.
Genes (Basel), 10(8).
https://doi.org/10.3390/genes10080576 Publication
Researcher Affiliations
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky 40546, USA.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky 40546, USA.
- Theriogenology Department, University of Mansoura, Mansoura 35516, Egypt.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky 40546, USA.
- Faculty of Veterinary Medicine, Ghent University, B-9820 Merelbeke, Belgium.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky 40546, USA.
- Department of Animal Reproduction, University of São Paulo, São Paulo 05508-270, Brazil.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky 40546, USA.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky 40546, USA.
- Department of Biomedical and Diagnostic Sciences, University of Tennessee, TN 37996, USA.
- Department of Biomedical and Diagnostic Sciences, University of Tennessee, TN 37996, USA.
- Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky 40546, USA. b.a.ball@uky.edu.
- Department of Animal Science, University of Kentucky, Lexington, KY 40546, USA. b.a.ball@uky.edu.
MeSH Terms
- Animals
- Blood Urea Nitrogen
- Diet, High-Protein / adverse effects
- Endometrium / metabolism
- Female
- Fertility
- Horses / blood
- Horses / genetics
- Horses / physiology
- Transcriptome
Conflict of Interest Statement
The authors declare no conflict of interest.
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