Angiogenesis and vascular endothelial growth factor expression in the equine corpus luteum.
Abstract: Precise pharmacological control of the corpus luteum is important in the manipulation of the oestrous cycle in mares. Angiogenesis plays a key role in the growth and regression of the corpus luteum; therefore, influencing the vasculature of the corpus luteum may offer a novel method for controlling its lifespan. In the present study, changes in angiogenesis and vascular expression of endothelial growth factor (VEGF) were evaluated throughout the luteal phase and after PGF(2alpha)-induced luteolysis. Corpora lutea were collected from mares in the early luteal phase (days 3-4), mid-luteal phase (day 10), early regression (day 14), late regression (day 17), and at 12 and 36 h after administration of PGF(2alpha) on day 10 of the oestrous cycle. Immunohistochemistry was used to localize Von Willebrand factor and Ki67 in endothelial and proliferating cells, respectively. VEGF mRNA and protein were localized by in situ hybridization and immunohistochemistry. The proliferation index of endothelial cells was intense in the early luteal phase. The early and mid-luteal phases were characterized by a dense network of capillaries. The microvasculature started to regress by day 14. After administration of PGF(2alpha), vasodilation was observed after 12 h, but after 36 h, luteal degeneration was accompanied by a significant decrease in vascularity. VEGF mRNA and protein were expressed mainly in the luteal cells during the early and mid-luteal phases and expression declined at early regression (day 14). However, immunostaining for VEGF protein was high in late luteal regression (day 17) and 36 h after PGF(2alpha) administration. These findings indicate a close temporal association between VEGF expression and angiogenesis in the equine corpus luteum during its functional lifespan.
Publication Date: 2003-02-13 PubMed ID: 12578540
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research investigated changes in angiogenesis and vascular expression of the growth factor in a horse’s corpus luteum, examining its role in the ovulation cycle and its potential for pharmaceutical control.
Understanding the Research
- The study was focused on the corpus luteum, an important element in the female reproductive cycle. When a female ovulates, the follicle that releases the egg transforms into the corpus luteum, which then produces progesterone. This hormone is essential for the maintenance of pregnancy in the early stages.
- The researchers hypothesized that controlling vasculature within the corpus luteum could provide a new method for manipulating its lifespan. The lifespan of the corpus luteum is of interest because it directly affects the length and duration of a female’s ovulation cycle, and therefore her fertility.?
The Research Method
- Scientists extracted corpora lutea from female horses at various stages of the ovulation cycle: early luteal (days 3-4), mid-luteal (day 10), early regression (day 14), late regression (day 17), and at 12 and 36 hours following administration of a substance known as PGF(2alpha), which induces luteolysis, or breakdown of the corpus luteum.?
- They then used immunohistochemistry to locate Von Willebrand factor and Ki67 in endothelial and proliferating cells, and to track the localization of VEGF mRNA and protein.
The Results
- The researchers found that endothelial cell proliferation was at its highest during the early luteal phase, recognized by a dense network of capillaries. By day 14, the microvasculature had started to regress.?
- Upon administration of PGF(2alpha), vasodilation (widening of blood vessels) was observed after 12 hours and after 36 hours, luteal degeneration was observed alongside a significant decrease in vascularity.
- VEGF mRNA and protein were mainly expressed in the luteal cells during the early and mid-luteal phases. However, the expression declined during early regression (day 14). VEGF protein immunostaining was high in late luteal regression (day 17) and 36 hours after xadministration of PGF(2alpha).
The Implications
- The findings of this study suggest a close association between expression of VEGF and angiogenesis within the corpus luteum during its functional lifespan. Potentially, manipulation of this angiogenesis could therefore permit a degree of control over the lifespan of the corpus luteum, which would be valuable in fertility treatments.
- This study provides a basis from which further research could develop new pharmaceutical methods of controlling the ovulation cycle in horses, and may have implications for human fertility as well.
Cite This Article
APA
Al-zi'abi MO, Watson ED, Fraser HM.
(2003).
Angiogenesis and vascular endothelial growth factor expression in the equine corpus luteum.
Reproduction, 125(2), 259-270.
Publication
Researcher Affiliations
- Department of Veterinary Clinical Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.
MeSH Terms
- Animals
- Biomarkers / analysis
- Capillaries
- Cell Division
- Corpus Luteum / blood supply
- Corpus Luteum / chemistry
- Corpus Luteum / physiology
- Dinoprost / pharmacology
- Endothelial Growth Factors / analysis
- Endothelial Growth Factors / genetics
- Endothelium, Vascular / cytology
- Endothelium, Vascular / metabolism
- Female
- Horses / physiology
- Immunohistochemistry
- In Situ Hybridization
- Intercellular Signaling Peptides and Proteins / analysis
- Intercellular Signaling Peptides and Proteins / genetics
- Ki-67 Antigen / analysis
- Luteal Phase / metabolism
- Lymphokines / analysis
- Lymphokines / genetics
- Neovascularization, Physiologic
- RNA, Messenger / analysis
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
- von Willebrand Factor / analysis
Citations
This article has been cited 9 times.- Billhaq DH, Lee S. The Role of the Guanosine Nucleotide-Binding Protein in the Corpus Luteum.. Animals (Basel) 2021 May 24;11(6).
- Billhaq DH, Lee S. A potential function of RLIP76 in the ovarian corpus luteum.. J Ovarian Res 2019 Apr 18;12(1):34.
- Kakuta H, Iguchi T, Sato T. The Involvement of Granulosa Cells in the Regulation by Gonadotropins of Cyp17a1 in Theca Cells.. In Vivo 2018 Nov-Dec;32(6):1387-1401.
- Hułas-Stasiak M, Dobrowolski P, Pawlikowska-Pawlęga B, Tomaszewska E, Muszyński S. The effects of dexamethasone administered during pregnancy on the postpartum spiny mouse ovary.. PLoS One 2017;12(8):e0183528.
- Alves KA, Alves BG, Gastal GD, de Tarso SG, Gastal MO, Figueiredo JR, Gambarini ML, Gastal EL. The Mare Model to Study the Effects of Ovarian Dynamics on Preantral Follicle Features.. PLoS One 2016;11(2):e0149693.
- Yoshioka S, Abe H, Sakumoto R, Okuda K. Proliferation of luteal steroidogenic cells in cattle.. PLoS One 2013;8(12):e84186.
- Galvão AM, Ferreira-Dias G, Skarzynski DJ. Cytokines and angiogenesis in the corpus luteum.. Mediators Inflamm 2013;2013:420186.
- Ribeiro LA, Turba ME, Zannoni A, Bacci ML, Forni M. Gelatinases, endonuclease and Vascular Endothelial Growth Factor during development and regression of swine luteal tissue.. BMC Dev Biol 2006 Nov 30;6:58.
- Fraser HM, Wulff C. Angiogenesis in the corpus luteum.. Reprod Biol Endocrinol 2003 Nov 10;1:88.
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