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Placenta2020; 93; 101-112; doi: 10.1016/j.placenta.2020.03.001

Equine hydrallantois is associated with impaired angiogenesis in the placenta.

Abstract: Hydrallantois is the excessive accumulation of fluid in the allantoic cavities during the last trimester of pregnancy, leading to abdominal wall hernias, cardiovascular shock, abortion, and dystocia. It has been postulated that hydrallantois is associated with structural and/or functional changes in the chorioallantoic membrane. In the present study, we hypothesized that angiogenesis is impaired in the hydrallantoic placenta. Capillary density in the hydrallantoic placenta was evaluated in the chorioallantois via immunohistochemistry for Von Willebrand Factor. Moreover, the expression of angiogenic genes was compared between equine hydrallantois and age-matched, normal placentas. In the hydrallantoic samples, edema was the main pathological finding. The capillary density was significantly lower in the hydrallantoic samples than in normal placentas. The reduction in the number of vessels was associated with abnormal expression of a subset of angiogenic and hypoxia-associated genes including VEGF, VEGFR1, VEGFR2, ANGPT1, eNOS and HIF1A. We believe that the capillary density and the abnormal expression of angiogenic genes leads to tissue hypoxia (high expression of HIF1A) and edema. Finally, we identified a lower expression of genes associated with steroidogenic enzyme (CYP19A1) and estrogen receptor signaling (ESR2) in the hydrallantoic placenta. Based on the presented data, we believe that formation of edema is due to disrupted vascular development (low number of capillaries) and hypoxia in the hydrallantoic placenta. The edema leads to further hypoxia and consequently, causes an increase in vessel permeability which leads to a gradual increase in interstitial fluid accumulation, resulting in an insufficient transplacental exchange rate and accumulation of fluid in the allantoic cavity.
Publication Date: 2020-03-05 PubMed ID: 32250734DOI: 10.1016/j.placenta.2020.03.001Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research article explores how the condition known as equine hydrallantois, characterized by excessive fluid accumulation in the allantoic cavities during late-stage pregnancy, is linked to impaired angiogenesis in the placenta. Lower capillary density and abnormal expression of angiogenic genes leading to tissue hypoxia and fluid buildup were found in hydrallantoic placentas.

Research Hypothesis and Method

  • The researchers began their study with a hypothesis that the development of new blood vessels, or angiogenesis, was compromised in the placenta in cases of hydrallantois.
  • To investigate this, they evaluated capillary density in the chorioallantois membrane using immunohistochemistry for Von Willebrand Factor, which is involved in blood clotting.
  • They also compared the gene expression related to angiogenesis in equine hydrallantois placentas with that in age-matched, normal placentas.

Key Findings

  • The researchers found that in the hydrallantoic samples, edema or swelling due to excess fluid buildup was the primary pathological finding.
  • Moreover, the capillary density was significantly lower in these hydrallantoic samples compared to normal placentas.
  • This reduction in the blood vessel count was linked to abnormal expression of certain genes tied to angiogenesis and hypoxia (low oxygen levels), such as VEGF, VEGFR1, VEGFR2, ANGPT1, eNOS, and HIF1A.

Implication of the Findings

  • The researchers concluded that the lower capillary density and the irregular gene expression contributes to tissue hypoxia and fluid buildup.
  • They found a lower expression of genes associated with steroidogenic enzyme (CYP19A1) and estrogen receptor signaling (ESR2) in the hydrallantoic placenta.
  • Based on the collected data, they speculated that the formation of edema was due to the disrupted development of blood vessels and hypoxia in the hydrallantoic placenta.
  • This edema further exacerbates hypoxia, which in turn increases blood vessel permeability. This sequence of events triggers a gradual rise in the volume of interstitial fluid and results in a lack of sufficient transplacental exchange rate. Consequently, fluid accumulation occurs in the allantoic cavity, making conditions like hydrallantois increasingly likely.

Cite This Article

APA
Dini P, Carossino M, Loynachan AT, El-Sheikh Ali H, Wolfsdorf KE, Scoggin KE, Daels P, Ball BA. (2020). Equine hydrallantois is associated with impaired angiogenesis in the placenta. Placenta, 93, 101-112. https://doi.org/10.1016/j.placenta.2020.03.001

Publication

ISSN: 1532-3102
NlmUniqueID: 8006349
Country: Netherlands
Language: English
Volume: 93
Pages: 101-112
PII: S0143-4004(20)30081-3

Researcher Affiliations

Dini, Pouya
  • Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium; Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
Carossino, Mariano
  • Louisiana Animal Disease Diagnostic Laboratory and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
Loynachan, Alan T
  • Veterinary Diagnostic Laboratory, 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.
Wolfsdorf, Karen E
  • Hagyard Equine Medical Institute, Lexington, KY, USA.
Scoggin, Kirsten E
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.
Daels, Peter
  • 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. Electronic address: b.a.ball@uky.edu.

MeSH Terms

  • Allantois / metabolism
  • Allantois / pathology
  • Animals
  • Female
  • Horse Diseases / genetics
  • Horse Diseases / pathology
  • Horse Diseases / physiopathology
  • Horses
  • Microvascular Density
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / physiopathology
  • Placenta / blood supply
  • Placenta / metabolism
  • Placenta / pathology
  • Placenta / physiopathology
  • Placenta Diseases / genetics
  • Placenta Diseases / pathology
  • Placenta Diseases / physiopathology
  • Placenta Diseases / veterinary
  • Polyhydramnios / etiology
  • Polyhydramnios / pathology
  • Polyhydramnios / physiopathology
  • Polyhydramnios / veterinary
  • Pregnancy
  • Pregnancy, Animal
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-1 / genetics
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Conflict of Interest Statement

Declaration of competing interest The authors declare that they have no competing interests.

Citations

This article has been cited 6 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. Ellero N, Lanci A, Baldassarro VA, Alastra G, Mariella J, Cescatti M, Giardino L, Castagnetti C. Study on NGF and VEGF during the Equine Perinatal Period-Part 1: Healthy Foals Born from Normal Pregnancy and Parturition. Vet Sci 2022 Aug 23;9(9).
    doi: 10.3390/vetsci9090451pubmed: 36136667google scholar: lookup
  3. Wang N, Shi D, Li N, Qi H. Clinical value of serum VEGF and sFlt-1 in pernicious placenta previa. Ann Med 2021 Dec;53(1):2041-2049.
    doi: 10.1080/07853890.2021.1999492pubmed: 34927512google scholar: lookup
  4. 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
  5. El-Sheikh Ali H, Loux SC, Kennedy L, Scoggin KE, Dini P, Fedorka CE, Kalbfleisch TS, Esteller-Vico A, Horohov DW, Erol E, Carter CN, Smith JL, Ball BA. Transcriptomic analysis of equine chorioallantois reveals immune networks and molecular mechanisms involved in nocardioform placentitis. Vet Res 2021 Jul 8;52(1):103.
    doi: 10.1186/s13567-021-00972-4pubmed: 34238364google scholar: lookup
  6. Dini P, Kalbfleisch T, Uribe-Salazar JM, Carossino M, Ali HE, Loux SC, Esteller-Vico A, Norris JK, Anand L, Scoggin KE, Rodriguez Lopez CM, Breen J, Bailey E, Daels P, Ball BA. Parental bias in expression and interaction of genes in the equine placenta. Proc Natl Acad Sci U S A 2021 Apr 20;118(16).
    doi: 10.1073/pnas.2006474118pubmed: 33853939google scholar: lookup