Seasonal expressions of VEGF and its receptors VEGFR1 and VEGFR2 in the prostate of the wild ground squirrels (Spermophilus dauricus)

  • Yuchen Yao Laboratory of Animal Physiology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, China.
  • Wenqian Xie Laboratory of Animal Physiology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, China.
  • Di Chen Laboratory of Animal Physiology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, China.
  • Yingying Han Laboratory of Animal Physiology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, China.
  • Zhengrong Yuan Laboratory of Animal Physiology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, China. https://orcid.org/0000-0002-5175-0675
  • Haolin Zhang Laboratory of Animal Physiology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, China.
  • Qiang Weng | qiangweng@bjfu.edu.cn Laboratory of Animal Physiology, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, China.

Abstract

As a vital male accessory reproductive gonad, the prostate requires vascular endothelial growth factors for promoting its growth and development. In this study, we investigated the localizations and expressions of vascular endothelial growth factor (VEGF) and its receptors including VEGF-receptor1 (VEFGR1) and VEGF-receptor2 (VEGFR2) in the prostate of the wild ground squirrels during the breeding and the non-breeding seasons. The values of total prostate weight and volume in the breeding season were higher than those in the non-breeding season. Histological observations showed that the exocrine lumens of the prostate expanded in the breeding season and contracted in the non-breeding season. The mRNA expression levels of VEGF and VEGFR2 in the prostate were higher in the breeding season than those in the non-breeding season, but the mRNA expression level of VEGFR1 had no significant change between the breeding and non-breeding seasons. Immunohistochemical results revealed that VEGF, VEGFR1 and VEGFR2 were presented in epithelial and stromal cells during the breeding and non-breeding seasons. In addition, the microvessels of the prostate were widely distributed and the number of microvessels increased obviously in the breeding season, while decreased sharply in the non-breeding season. These results suggested that expression levels of VEGF and VEGFR2 might be correlated with seasonal changes in morphology and functions of the prostate, and VEGF might serve as pivotal regulators to affect seasonal changes in the prostate functions of the wild male ground squirrels via an autocrine/paracrine pathway.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

References

Powers GL, Marker PC. Recent advances in prostate development and links to prostatic diseases. Wiley Interdiscip Rev Syst Biol Med 2013;5:243-56. DOI: https://doi.org/10.1002/wsbm.1208

Cook C, Vezina CM, Allgeier SH, Shaw A, Yu M, Peterson RE, et al. Noggin is required for normal lobe patterning and ductal budding in the mouse prostate. Dev Biol 2007;312:217-30. DOI: https://doi.org/10.1016/j.ydbio.2007.09.038

Wang GC, Zhao D, Spring DJ, DePinho RA. Genetics and biology of prostate cancer. Genes Dev 2018;32:1105-40. DOI: https://doi.org/10.1101/gad.315739.118

Omabe M, Ezeani M. Infection, inflammation and prostate carcinogenesis. Infect Genet Evol 2011;11:1195-8. DOI: https://doi.org/10.1016/j.meegid.2011.03.002

Singh M, Jha R, Melamed J, Shapiro E, Hayward SW, Lee P. Stromal androgen receptor in prostate development and cancer. Am J Pathol 2014;184:2598-607. DOI: https://doi.org/10.1016/j.ajpath.2014.06.022

Hoover P, Naz RK. Do men with prostate abnormalities (prostatitis/benign prostatic hyperplasia/prostate cancer) develop immunity to spermatozoa or seminal plasma? Int J Androl 2012;35:608-15. DOI: https://doi.org/10.1111/j.1365-2605.2011.01246.x

Kumar VL, Majumder PK. Prostate: structure, functions and regulation. Int Urol Nephrol 1995;27:231-43. DOI: https://doi.org/10.1007/BF02564756

Ceci C, Atzori MG, Lacal PM, Graziani G. Role of VEGFs/VEGFR-1 signaling and its inhibition in modulating tumor invasion: Experimental evidence in different metastatic cancer models. Int J Mol Sci 2020;21:1388. DOI: https://doi.org/10.3390/ijms21041388

Langan RC. Benign prostatic hyperplasia. Prim Care. 2019;46:223-32. DOI: https://doi.org/10.1016/j.pop.2019.02.003

Fantone S, Tossetta G, Montironi R, Senzacqua M, Marzioni D, Mazzucchelli R. Ciliary neurotrophic factor (CNTF) and its receptor (CNTFRα) signal through MAPK/ERK pathway in human prostate tissues: a morphological and biomolecular study. Eur J Histochem 2020;64:3147. DOI: https://doi.org/10.4081/ejh.2020.3147

Apte RS, Chen DS, Ferrara N. VEGF in signaling and disease: Beyond discovery and development. Cell 2019;176:1248-64. DOI: https://doi.org/10.1016/j.cell.2019.01.021

Melincovici CS, Boşca AB, Şuşman S, Mărginean M, Mihu C, Istrate M, et al. Vascular endothelial growth factor (VEGF) - key factor in normal and pathological angiogenesis. Rom J Morphol Embryol 2018;59:455-67.

Zhang QY, Qiu SD, Ge L. Studies on expression and location of VEGF protein in rat testis and epididymis. Shi Yan Sheng Wu Xue Bao 2004;37:1-8.

Grivas N, Goussia A, Stefanou D, Giannakis D. Microvascular density and immunohistochemical expression of VEGF, VEGFR-1 and VEGFR-2 in benign prostatic hyperplasia, high-grade prostate intraepithelial neoplasia and prostate cancer. Cent European J Urol 2016;69:63-71.

Movsas TZ, Sigler R, Muthusamy A. Vitreous levels of luteinizing hormone and VEGF are strongly correlated in healthy mammalian eyes. Curr Eye Res 2018;43:1041-4. DOI: https://doi.org/10.1080/02713683.2018.1467932

Movsas TZ, Sigler R, Muthusamy A. Elimination of signaling by the luteinizing hormone receptor reduces ocular VEGF and retinal vascularization during mouse eye development. Curr Eye Res 2018;43:1286-9. DOI: https://doi.org/10.1080/02713683.2018.1495740

Kazi AA, Molitoris KH, Koos RD. Estrogen rapidly activates the PI3K/AKT pathway and hypoxia-inducible factor 1 and induces vascular endothelial growth factor A expression in luminal epithelial cells of the rat uterus. Biol Reprod 2009;81:378-87. DOI: https://doi.org/10.1095/biolreprod.109.076117

Yang M, Wang L, Wang X, Wang XZ, Yang ZQ, Li JX. IL-6 promotes FSH-induced VEGF expression through JAK/STAT3 signaling pathway in bovine granulosa cells. Cell Physiol Biochem 2017;44:293-302. DOI: https://doi.org/10.1159/000484885

Rudolfsson SH, Wikström P, Jonsson A, Collin O, Bergh A. Hormonal regulation and functional role of vascular endothelial growth factor a in the rat testis. Biol Reprod 2004;70:340-7. DOI: https://doi.org/10.1095/biolreprod.103.016816

Hwang GS, Wang SW, Tseng WM, Yu CH, Wang PS. Effect of hypoxia on the release of vascular endothelial growth factor and testosterone in mouse TM3 Leydig cells. Am J Physiol Endocrinol Metab 2007;292:E1763-E1769. DOI: https://doi.org/10.1152/ajpendo.00611.2006

Eisermann K, Fraizer G. The androgen receptor and VEGF: Mechanisms of androgen-regulated angiogenesis in prostate cancer. Cancers (Basel) 2017;9:32. DOI: https://doi.org/10.3390/cancers9040032

Ma T, Yang SL, Jing HY, Cong L, Cao ZX, Liu ZL, et al. Apparent diffusion coefficients in prostate cancer: correlation with molecular markers Ki-67, HIF-1α and VEGF. NMR Biomed 2018;31:nbm.3884. DOI: https://doi.org/10.1002/nbm.3884

Wang Y, Wang ZY, Yu WY, Sheng X, Zhang HL, Han YY, et al. Seasonal expressions of androgen receptor, estrogen receptors and cytochrome P450 aromatase in the uteri of the wild Daurian ground squirrels (Spermophilus dauricus). Eur J Histochem 2018;62:2889. DOI: https://doi.org/10.4081/ejh.2018.2889

Han YY, Zhan JQ, Xu Y, Zhang FW, Yuan ZR, Weng Q. Proliferation and apoptosis processes in the seasonal testicular development of the wild Daurian ground squirrel (Citellus dauricus Brandt, 1844). Reprod Fertil Dev 2017;29:1680-8. DOI: https://doi.org/10.1071/RD16063

Li QL, Zhang FW, Zhang S, Sheng X, Han YY, Weng Q, et al. Seasonal expression of androgen receptor, aromatase, and estrogen receptor alpha and beta in the testis of the wild ground squirrel (Citellus dauricus Brandt). Eur J Histochem 2015;59:2456.

Wang Y, Yao YC, Zhang CJ, Guo YY, Zhang HL, Han YY, et al. Seasonal expressions of COX-1, COX-2 and EP4 in the uteri of the wild Daurian ground squirrels (Spermophilus dauricus). Prostains Other Lipid Mediat 2019;143:106343. DOI: https://doi.org/10.1016/j.prostaglandins.2019.106343

Zhang Y, Wang Y, Huang C, Wang Y, Qi HY, Han YY, et al. Seasonal expression of 5α-reductases and androgen receptor in the prostate of the wild ground squirrel (Spermophilus dauricus). Comp Biochem Physiol A Mol Integr Physiol 2018;226:11-6. DOI: https://doi.org/10.1016/j.cbpa.2018.06.023

Weng JJ, Li B, Sheng X, Zhang HL, Hu X, Zhou J, et al. Seasonal changes in immunoreactivity of vascular endothelial factor and its receptors VEGFR1 and VEGFR2 in the uterus of wild ground squirrels (Citellus dauricus Brandt). J Reprod Dev 2012;58:537-43. DOI: https://doi.org/10.1262/jrd.2012-024

Jiménez R, Burgos M, Barrionuevo FJ. Circannual testis changes in seasonally breeding mammals. Sex Dev 2015;9:205-25. DOI: https://doi.org/10.1159/000439039

Qiang W, Murase T, Tsubota T. Seasonal changes in spermatogenesis and testicular steroidogenesis in wild male raccoon dogs (Nyctereutes procynoides). J Vet Med Sci 2003;65:1087-92. DOI: https://doi.org/10.1292/jvms.65.1087

Tsubota T, Howell-Skalla L, Nitta H, Osawa Y, Mason JI, Meiers PG, et al. Seasonal changes in spermatogenesis and testicular steroidogenesis in the male black bear Ursus americanus. J Reprod Fertil 1997;109:21-7. DOI: https://doi.org/10.1530/jrf.0.1090021

Klonisch T, Schön J, Hombach-Klonisch S, Blottner S. The roe deer as a model for studying seasonal regulation of testis function. Int J Androl 2006;29:122-8. DOI: https://doi.org/10.1111/j.1365-2605.2005.00603.x

Williams CT, Klaassen M, Barnes BM, Buck CL, Arnold W, Giroud S, et al. Seasonal reproductive tactics: annual timing and the capital-to-income breeder continuum. Philos Trans R Soc Lond B Biol Sci 2017;372:20160250. DOI: https://doi.org/10.1098/rstb.2016.0250

Breier G, Damert A, Plate KH, Risau W. Angiogenesis in embryos and ischemic diseases. Thromb Haemost 1997;78:678-83. DOI: https://doi.org/10.1055/s-0038-1657611

Pandya NM, Dhalla NS, Santani DD. Angiogenesis--a new target for future therapy. Vascul Pharmacol 2006;44:265-74. DOI: https://doi.org/10.1016/j.vph.2006.01.005

Ferrer FA, Miller LJ, Andrawis RI, Kurtzman SH, Albertsen PC, Laudone VP, et al. Vascular endothelial growth factor (VEGF) expression in human prostate cancer: in situ and in vitro expression of VEGF by human prostate cancer cells. J Urol 1997;157:2329-33. DOI: https://doi.org/10.1016/S0022-5347(01)64775-X

Woollard DJ, Opeskin K, Coso S, Wu D, Baldwin ME, Williams ED. Differential expression of VEGF ligands and receptors in prostate cancer. Prostate 2013;73:563-72. DOI: https://doi.org/10.1002/pros.22596

Palmieri C. Immunohistochemical expression of angiogenic factors by neoplastic epithelial cells is associated with canine prostatic carcinogenesis. Vet Pathol 2015;52:607-13. DOI: https://doi.org/10.1177/0300985814549951

Chen Z, Yao YC, Shen YY, Zhang A, Zhang Y, Xie W, et al. Seasonal expressions of prostaglandin E synthases and receptors in the prostate of the wild ground squirrel (Spermophilus dauricus). Prostaglandins Other Lipid Mediat 2020;148:106412. DOI: https://doi.org/10.1016/j.prostaglandins.2020.106412

Sampson N, Madersbacher S, Berger P. [Pathophysiologie und Therapie der benignen Prostata-Hyperplasie(Pathophysiology and therapy of benign prostatic hyperplasia)].[Article in German]. Wien Klin Wochenschr 2008;120:390-401. DOI: https://doi.org/10.1007/s00508-008-0986-5

Lissbrant IF, Hammarsten P, Lissbrant E, Ferrara N, Rudolfsson SH, Bergh A. Neutralizing VEGF bioactivity with a soluble chimeric VEGF-receptor protein flt(1-3)IgG inhibits testosterone-stimulated prostate growth in castrated mice. Prostate 2004;58:57-65. DOI: https://doi.org/10.1002/pros.10312

Sinowatz F, Amselgruber W, Plendl J, Kölle S, Neumüller C, Boos G. Effects of hormones on the prostate in adult and aging men and animals. Microsc Res Tech 1995;30:282-92. DOI: https://doi.org/10.1002/jemt.1070300404

Joseph IB, Nelson JB, Denmeade SR, Isaacs JT. Androgens regulate vascular endothelial growth factor content in normal and malignant prostatic tissue. Clin Cancer Res 1997;3:2507-11.

Wang L, Chen ZJ, Wang QT, Cao WF, Jian Y, Wang SX, et al. Expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor in prostate cancer and its significance. Zhonghua Nan Ke Xue 2006;12:57-9.

Lohela M, Bry M, Tammela T, Alitalo K. VEGFs and receptors involved in angiogenesis versus lymphangiogenesis. Curr Opin Cell Biol 2009;21:154-65. DOI: https://doi.org/10.1016/j.ceb.2008.12.012

Published
2021-03-24
Info
Issue
Section
Articles
Ethics Approval
All the procedures on animals were carried out in accordance with the policy on the Care and Use of Animals by the Ethical Committee, Beijing Forestry University and approved by the Department of Agriculture of Hebei province, China (JNZF11/2007).
Supporting Agencies
National Natural Science Foundation of China, Natural Science Foundation of Beijing, Young Scientist Start-up funding of Beijing Forestry University
Keywords:
Prostate, VEGF, VEGFR1, VEGFR2, wild ground squirrel
Statistics
  • Abstract views: 143

  • PDF: 51
  • HTML: 0
How to Cite
Yao, Y., Xie, W., Chen, D., Han, Y., Yuan, Z., Zhang, H., & Weng, Q. (2021). Seasonal expressions of VEGF and its receptors VEGFR1 and VEGFR2 in the prostate of the wild ground squirrels (<em>Spermophilus dauricus</em&gt;). European Journal of Histochemistry, 65(2). https://doi.org/10.4081/ejh.2021.3219