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Biology of reproduction2021; 104(6); 1386-1399; doi: 10.1093/biolre/ioab039

Paternally expressed retrotransposon Gag-like 1 gene, RTL1, is one of the crucial elements for placental angiogenesis in horses†.

Abstract: RTL1 (retrotransposon Gag-like 1) is an essential gene in the development of the human and murine placenta. Several fetal and placental abnormalities such as intrauterine growth restriction (IUGR) and hydrops conditions have been associated with altered expression of this gene. However, the function of RTL1 has not been identified. RTL1 is located on a highly conserved region in eutherian mammals. Therefore, the genetic and molecular analysis in horses could hold important implications for other species, including humans. Here, we demonstrated that RTL1 is paternally expressed and is localized within the endothelial cells of the equine (Equus caballus) chorioallantois. We developed an equine placental microvasculature primary cell culture and demonstrated that RTL1 knockdown leads to loss of the sprouting ability of these endothelial cells. We further demonstrated an association between abnormal expression of RTL1 and development of hydrallantois. Our data suggest that RTL1 may be essential for placental angiogenesis, and its abnormal expression can lead to placental insufficiency. This placental insufficiency could be the reason for IUGR and hydrops conditions reported in other species, including humans.
Publication Date: 2021-03-12 PubMed ID: 33693478DOI: 10.1093/biolre/ioab039Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The researchers established that the retrotransposon Gag-like 1 (RTL1) gene, primarily expressed paternally, is critical for the development of the horse’s placenta, with its malfunction potentially leading to several abnormalities such as placental insufficiency.

Understanding RTL1

  • The gene known as RTL1 (retrotransposon Gag-like 1) plays a crucial role in the formation of the placenta in both humans and mice. Its abnormal expression has been linked to several fetal and placental disorders such as intrauterine growth restriction (IUGR) and hydrops conditions.
  • Despite extensive studies, the function of RTL1 has not been clearly defined. Notably, RTL1 can be found in a highly conserved region among eutherian mammals, implying that the gene, its mutations, and its functions could possibly share similarities across species.

The Role of RTL1 in Horses

  • The researchers in this study concentrated their efforts on investigating RTL1’s role in horses (Equus caballus). They found that the gene is paternally expressed, and it is localized within the endothelial cells of the equine chorioallantois, a significant part of the placenta in horses.
  • With the development of an equine placental microvasculature primary cell culture, the research team demonstrated that knocking down the RTL1 gene resulted in a loss of sprouting abilities in these endothelial cells. This suggests they play a key role in the formation of new blood vessels, a process known as angiogenesis.

Implications of Abnormal RTL1 Expression

  • Furthermore, the researchers noticed an association between abnormal RTL1 expression and the development of hydrallantois, an abnormal accumulation of fluid in the allantoic cavity during pregnancy in mares.
  • The data collected suggests that RTL1 is vital for placental angiogenesis – the formation of new blood vessels within the placenta. Misexpression of RTL1 can lead to placental insufficiency, a condition where the placenta doesn’t work efficiently, not being able to fully support the fetus.
  • This placental insufficiency could be the reason behind cases of intrauterine growth restriction (IUGR) and hydrops conditions reported in other species, including humans. Thus, understanding the role and behavior of RTL1 in horses could provide insights into its function and implications in other species.

Cite This Article

APA
Dini P, Carossino M, Balasuriya UBR, El-Sheikh Ali H, Loux SC, Esteller-Vico A, Scoggin KE, Loynachan AT, Kalbfleisch T, De Spiegelaere W, Daels P, Ball BA. (2021). Paternally expressed retrotransposon Gag-like 1 gene, RTL1, is one of the crucial elements for placental angiogenesis in horses†. Biol Reprod, 104(6), 1386-1399. https://doi.org/10.1093/biolre/ioab039

Publication

ISSN: 1529-7268
NlmUniqueID: 0207224
Country: United States
Language: English
Volume: 104
Issue: 6
Pages: 1386-1399

Researcher Affiliations

Dini, Pouya
  • Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
Carossino, Mariano
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
Balasuriya, Udeni B R
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
El-Sheikh Ali, Hossam
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
  • Theriogenology Department, Faculty of Veterinary Medicine, University of Mansoura, Mansoura, Egypt.
Loux, Shavahn C
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
Esteller-Vico, Alejandro
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
Scoggin, Kirsten E
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
Loynachan, Alan T
  • Veterinary Diagnostic Laboratory, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
Kalbfleisch, Theodore
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
De Spiegelaere, Ward
  • Department of Morphology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Daels, Peter
  • Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
Ball, Barry A
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.

MeSH Terms

  • Animals
  • Female
  • Horses / genetics
  • Horses / physiology
  • Placenta / physiology
  • Pregnancy
  • Pregnancy Proteins / genetics
  • Pregnancy Proteins / metabolism

Citations

This article has been cited 2 times.
  1. Orellana-Guerrero D, Uribe-Salazar JM, El-Sheikh Ali H, Scoggin KE, Ball B, Daels P, Finno CJ, Dini P. Dynamics of the Equine Placental DNA Methylome and Transcriptome from Mid- to Late Gestation.. Int J Mol Sci 2023 Apr 11;24(8).
    doi: 10.3390/ijms24087084pubmed: 37108254google scholar: lookup
  2. Haneda S, Dini P, Esteller-Vico A, Scoggin KE, Squires EL, Troedsson MH, Daels P, Nambo Y, Ball BA. Estrogens Regulate Placental Angiogenesis in Horses.. Int J Mol Sci 2021 Nov 9;22(22).
    doi: 10.3390/ijms222212116pubmed: 34829994google scholar: lookup