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Reproductive biology and endocrinology : RB&E2017; 15(1); 4; doi: 10.1186/s12958-016-0223-4

Hexokinase 2 drives glycogen accumulation in equine endometrium at day 12 of diestrus and pregnancy.

Abstract: Secretion of histotroph during the prolonged pre-implantation phase in mares is crucial to pregnancy maintenance, manifested as increased embryonic loss in mares with age-related endometrial degeneration. Glycogen content of uterine histotroph is higher during the progesterone-dominated phase of the estrous cycle in mares, but regulatory mechanisms are not well understood. Methods: mRNA expression of glycogen-metabolizing enzymes (HK1, HK2, GSK3B, GYS1, PEPCK, PKM, PYGM) in endometrial samples were compared among mares in anestrus, estrus, and at Day 12 of diestrus and pregnancy. In addition, hexokinase 2 (HK2) activity was assessed using a colorimetric assay. Results: HK2 was the key regulator of glycogen accumulation during diestrus and pregnancy; hexokinase transcript abundance and enzyme activity were significantly higher during diestrus and pregnancy than estrus and anestrus. In addition, despite similar relative transcript abundance, hexokinase activity was significantly greater in the pregnant versus diestrous endometrium. Therefore, we inferred there was regulation of hexokinase activity through phosphorylation, in addition to its regulation at the transcriptional level during early pregnancy. Based on immunohistochemistry, HK2 was localized primarily in luminal and glandular epithelial cells, with weaker staining in stromal cells. Conclusions: Among glycogen metabolizing enzymes identified, expression of HK2 was significantly greater during the progesterone-dominated phase of the cycle.
Publication Date: 2017-01-05 PubMed ID: 28056994PubMed Central: PMC5217302DOI: 10.1186/s12958-016-0223-4Google Scholar: Lookup
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  • Journal Article

Summary

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The research investigates the role of hexokinase 2 (HK2), an enzyme involved in glycogen metabolism, in the equine endometrium during different stages of the reproductive cycle and early pregnancy. Findings reveal that HK2 drives glycogen accumulation during diestrus and pregnancy, crucial for successful pregnancy maintenance.

Methods

  • Endometrial samples were collected from mares during anestrus, estrus, day 12 of diestrus and pregnancy.
  • The presence and activity of glycogen-metabolizing enzymes HK1, HK2, GSK3B, GYS1, PEPCK, PKM, and PYGM were determined using mRNA expression analysis and a colorimetric assay for HK2 activity.
  • Immunohistochemistry was utilized to determine the location of HK2 within the endometrium cells.

Results

  • The study demonstrated a significant increase in both hexokinase transcript abundance and enzyme activity during diestrus and pregnancy as compared to estrus and anestrus.
  • Despite similar relative transcript levels, significantly higher hexokinase activity was observed in the pregnant endometrium compared to the diestrous state, indicating a possible regulation of the enzyme’s activity through phosphorylation during early pregnancy.
  • By using immunohistochemistry, the distribution of HK2 was found primarily in luminal and glandular epithelial endometrial cells, with minor presence in stromal cells.

Conclusions

  • Among all the glycogen-metabolizing enzymes under investigation, the study revealed that the expression of HK2 was significantly increased during the progesterone-dominated phase of the reproductive cycle in mares.
  • This provides evidence about the crucial role of HK2 in regulating glycogen accumulation in the equine endometrium during diestrus and pregnancy – a necessary process for successful pregnancy maintenance.
  • The study also hinted at the possibility of additional regulation of the enzyme through phosphorylation during early pregnancy.

Cite This Article

APA
Bramer SA, Macedo A, Klein C. (2017). Hexokinase 2 drives glycogen accumulation in equine endometrium at day 12 of diestrus and pregnancy. Reprod Biol Endocrinol, 15(1), 4. https://doi.org/10.1186/s12958-016-0223-4

Publication

ISSN: 1477-7827
NlmUniqueID: 101153627
Country: England
Language: English
Volume: 15
Issue: 1
Pages: 4
PII: 4

Researcher Affiliations

Bramer, Sarah A
  • Department of Veterinary and Clinical Diagnostic Sciences, University of Calgary, Faculty of Veterinary Medicine, 3280 Hospital Dr NW, Calgary, AB, T2N 4Z6, Canada.
Macedo, Alysson
  • Department of Veterinary and Clinical Diagnostic Sciences, University of Calgary, Faculty of Veterinary Medicine, 3280 Hospital Dr NW, Calgary, AB, T2N 4Z6, Canada.
Klein, Claudia
  • Department of Veterinary and Clinical Diagnostic Sciences, University of Calgary, Faculty of Veterinary Medicine, 3280 Hospital Dr NW, Calgary, AB, T2N 4Z6, Canada. claudia.klein@ucalgary.ca.

MeSH Terms

  • Animals
  • Diestrus / metabolism
  • Endometrium / chemistry
  • Endometrium / metabolism
  • Enzyme Activation / physiology
  • Female
  • Glycogen / analysis
  • Glycogen / metabolism
  • Hexokinase / analysis
  • Hexokinase / metabolism
  • Horses
  • Pregnancy / metabolism

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Citations

This article has been cited 4 times.
  1. Sun Y, Sun B, Wang Z, Lv Y, Ma Q. Short-Term Decreasing and Increasing Dietary BCAA Have Similar, but Not Identical Effects on Lipid and Glucose Metabolism in Lean Mice.. Int J Mol Sci 2023 Mar 11;24(6).
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  2. Diel de Amorim M, Klein C, Foster R, Dong L, Lopez-Rodriguez MF, Card C. Expression of Oxytocin/Neurophysin I and Oxytocinase in the Equine Conceptus from Day 8 to Day 21 Post-Ovulation.. Animals (Basel) 2022 Mar 22;12(7).
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  3. Schöniger S, Schoon HA. The Healthy and Diseased Equine Endometrium: A Review of Morphological Features and Molecular Analyses.. Animals (Basel) 2020 Apr 5;10(4).
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  4. Lavu N, Richardson L, Bonney E, Menon R. Glycogen synthase kinase (GSK) 3 in pregnancy and parturition: a systematic review of literature.. J Matern Fetal Neonatal Med 2020 Jun;33(11):1946-1957.
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