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Biomolecules2025; 15(8); 1135; doi: 10.3390/biom15081135

Gestation-Stage Related Changes in the IGF System Components in the Equine Placenta.

Abstract: The insulin-like growth factor (IGF) system regulates implantation, placental development, and angiogenesis in eutherian mammals. However, little is known about the changes in this system in equine placenta (chorioallantois; CA) and the endometrium (EN) during pregnancy, or the relationship to vascular endothelial growth factor () expression. The current study investigated the expression of the IGF system components, namely the ligands ( and ), their receptors (, , and ), and their binding proteins ( and s) in equine CA at 45 days, 4, 6, 10, and 11 months of gestational age (GA) and immediately postpartum (PP), and in equine EN at 4, 6, 10, and 11 months GA. IGF1 immunolocalization and serum concentrations were also evaluated across gestation. mRNA expression in CA increased from day 45 to peak at 6 months and then gradually declined to reach a nadir in PP samples. This profile correlated positively with the expression profile (r = 0.62, = 0.001). In contrast, expression in CA was not correlated with ( = 0.14). Interestingly, mRNA was more abundant in equine CA than ( < 0.05) throughout gestation. Among the IGFBPs investigated in CA, the expression of and was highly abundant ( < 0.05) at day 45 compared to other GAs. Conversely, mRNA expression for and was more abundant ( < 0.05) in PP than at all investigated GAs. Immunohistochemistry revealed that IGF1 is localized in the equine chorionic epithelium (cytoplasm and nucleus). IGF1 serum concentrations peaked at 9 months and declined to their lowest levels PP. In conclusion, this study demonstrates a positive correlation between and expression in equine CA during gestation, suggesting that the IGF system plays a crucial role in placental angiogenesis by regulating .
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Publication Date: 2025-08-06 PubMed ID: 40867581PubMed Central: PMC12384007DOI: 10.3390/biom15081135Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This study examined how the components of the insulin-like growth factor (IGF) system change in the horse placenta and endometrium throughout pregnancy.
  • It explored the relationship between IGF system expression and vascular endothelial growth factor (VEGF), suggesting the IGF system’s important role in placental blood vessel formation during gestation.

Background and Significance

  • The IGF system includes growth factors IGF1 and IGF2, their receptors (IGF1R, IGF2R, insulin receptor – INSR), and binding proteins (IGFBPs).
  • This system is known to regulate key reproductive processes such as embryo implantation, placental development, and angiogenesis (formation of new blood vessels) in mammals.
  • Understanding IGF system dynamics in the equine placenta (chorioallantois, CA) and endometrium (EN) is important because little data existed prior on how this system changes with gestational age in horses.
  • VEGF is a well-known factor involved in placental blood vessel growth; investigating its relationship with IGF components provides insights into placental angiogenesis regulation.

Study Design and Methods

  • Sample collection:
    • Equine chorioallantois tissues collected at 45 days, 4 months, 6 months, 10 months, 11 months of gestation, and immediately postpartum (PP).
    • Equine endometrial tissues collected at 4, 6, 10, and 11 months of gestation.
  • Investigated molecular components:
    • IGF ligands: IGF1 and IGF2
    • Receptors: IGF1R, IGF2R, and INSR
    • Binding proteins: several IGFBPs, notably IGFBP1, IGFBP2, IGFBP4, and IGFBP5
  • Techniques used:
    • Quantitative mRNA expression analysis
    • Immunohistochemistry for protein localization of IGF1 within tissues
    • Measurement of IGF1 concentration in maternal serum throughout pregnancy
    • Correlation studies between IGF system components and VEGF (vascular endothelial growth factor) expression

Key Findings

  • IGF2 expression pattern in chorioallantois (CA):
    • mRNA expression increased from day 45 post-fertilization, peaked by 6 months gestation, then declined steadily until lowest levels immediately postpartum.
    • This expression profile positively correlated with the mRNA expression of VEGF (correlation coefficient r = 0.62, p = 0.001), supporting a link between IGF2 and placental angiogenesis.
  • IGF1 in chorioallantois:
    • IGF1 mRNA was consistently more abundant than IGF2 throughout gestation (statistically significant, p < 0.05).
    • IGF1 protein localized specifically in the chorionic epithelium cells’ cytoplasm and nucleus, indicating its functional relevance in this tissue.
    • Serum IGF1 concentrations peaked at 9 months gestation and fell to lowest levels after birth, indicating systemic regulation of IGF1 linked to pregnancy stage.
  • IGF receptors and binding proteins in the placenta:
    • The study highlights differential expression of receptors but focuses mainly on IGFBPs.
    • IGFBP1 and IGFBP2 had high expression at early gestation (day 45), suggesting a role in early placental development or implantation.
    • IGFBP4 and IGFBP5 mRNA levels were significantly higher postpartum than at any gestational age examined, implying roles perhaps in placental regression or remodeling after birth.
  • Correlation of IGF system components with VEGF:
    • Positive correlation between IGF2 and VEGF expression suggests IGF2’s involvement in stimulating placental blood vessel formation.
    • No significant correlation between IGF1 and VEGF, indicating different regulatory roles for the two IGFs.

Conclusions and Implications

  • The IGF system in the equine placenta changes dynamically throughout pregnancy, with distinct patterns for IGF1, IGF2, binding proteins, and receptors.
  • IGF2 expression closely links to VEGF, indicating that IGF2 likely supports placental angiogenesis in horses.
  • IGF1’s localization and serum profile suggest it also plays important but potentially different roles in pregnancy maintenance and fetal development.
  • These insights improve understanding of equine placental biology, which could have implications for managing equine pregnancy health and diagnosing gestational disorders.
  • The study provides a foundation for future research on therapeutic targets related to placental growth and function in horses and potentially other mammals.

Cite This Article

APA
Scoggin KE, Adlan F, Fedorka CE, Rakha SI, Stout TAE, Troedsson MHT, Ali HE. (2025). Gestation-Stage Related Changes in the IGF System Components in the Equine Placenta. Biomolecules, 15(8), 1135. https://doi.org/10.3390/biom15081135

Publication

Biomolecules
ISSN: 2218-273X
NlmUniqueID: 101596414
Country: Switzerland
Language: English
Volume: 15
Issue: 8
PII: 1135

Researcher Affiliations

Scoggin, Kirsten E
  • Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
Adlan, Fatma
  • Department of Theriogenology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.
Fedorka, Carleigh E
  • Department of Animal Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Rakha, Shimaa I
  • Department of Theriogenology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.
Stout, Tom A E
  • Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
Troedsson, Mats H T
  • Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
Ali, Hossam El-Sheikh
  • Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.

MeSH Terms

  • Animals
  • Female
  • Horses
  • Pregnancy
  • Placenta / metabolism
  • Insulin-Like Growth Factor II / metabolism
  • Insulin-Like Growth Factor II / genetics
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Gestational Age
  • Endometrium / metabolism
  • Insulin-Like Growth Factor Binding Proteins / metabolism
  • Insulin-Like Growth Factor Binding Proteins / genetics

Conflict of Interest Statement

The authors declare no conflicts of interest.

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