Journal of Isfahan Medical School

Journal of Isfahan Medical School

The Survey of Angiogenesis and Myometrial Thickness of Preimplantation Mouse Uterine in Natural Cycle in those Received Human Menopausal Gonadotropin-Human Chorionic Gonadotropin (HMG–HCG) and Sildenafil Citrate

Document Type : Original Article (s)

Authors
Gholamreza Dashti 1
Ariubarzan Farhadi 2
Mohammad Javad Saeedi-Borujeni 3
Bahman Rashidi 1
1 Associate Professor, Department of Anatomical Sciences and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
2 Student of Medicine, Student Research Committee, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
3 PhD Candidate, Department of Anatomical Sciences and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Abstract
Background: Uterus myometrium contractions play crucial role in break or successful embryo implantation. Furthermore, efficient myometrial angiogenesis is important event for supplying endometrium blood. Recently, many studies were performed for investigating the effects of sildenafil citrate (SC) on female fertility. This study aimed was to assess the changes in myometrial thickness and associated angiogenesis after injections of sildenafil citrate in superovulated mice.Methods: Thirty adult female mice and ten adult male mice were purchased. The female mice were divided into three equal groups of control without any intervention, gonadotropin receiving human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG), and gonadotropin and sildenafil citrate receiving human menopausal gonadotropin, and human chorionic gonadotropin and sildenafil citrate administration. After mating, animals were deeply anesthetized and the uterus was rapidly removed for histology and immunohistochemistry process to identify cluster of differentiation 31 (CD31).Findings: In gonadotropin + sildenafil citrate group, the thickness of myometrium was significantly thicker than control and gonadotropin groups (P < 0.05 for both). The results of immunohistochemistry survey for myometrium CD31 demonstrated that administrated sildenafil citrate did not induce any angiogenesis associated alteration in gonadotropin + sildenafil citrate group (P > 0.05).Conclusion: It may finally conclude that administration of sildenafil citrate does not cause remarkable alterations in myometrial angiogenesis; but increases the thickness of myometrium. Although for realistic decision about the sildenafil citrate effects on aforementioned parameters, more molecular investigations and longer drug consumption periods are necessary.
Keywords
Sildenafil citrate
Myometrium
Angiogenesis
  1. Nguyen TT, Shynlova O, Lye SJ. Matrix metalloproteinase expression in the rat myometrium during pregnancy, term labor, and postpartum. Biol Reprod 2016; 95(1): 24.
  2. Mandala M, Osol G. Physiological remodelling of the maternal uterine circulation during pregnancy. Basic Clin Pharmacol Toxicol 2012; 110(1): 12-8.
  3. Osol G, Moore LG. Maternal uterine vascular remodeling during pregnancy. Microcirculation 2014; 21(1): 38-47.
  4. Osol G, Mandala M. Maternal uterine vascular remodeling during pregnancy. Physiology (Bethesda) 2009; 24: 58-71.
  5. Rashidi B, Soleimani Rad JI, Roshangar L, Alizadeh MR. Evaluation of pinopodes expression on the mouse endometrium immediately before implantation by treatment with HMG/HCG and sildenafil citrate administration. Iran J Basic Med Sci 2012; 15(5): 1091-6.
  6. Rashidi B, Soleimani Rad J, Roshangar L. Comparison of morphological and morphometrical characteristics in the glandular epithelium of mouse endometrium in preimplantation period after administration HMG-HCG, progesterone and sildenafil citrate. J Isfahan Med Sch 2010; 28(112): 656-64. [In Persian].
  7. Sher G, Fisch JD. Vaginal sildenafil (Viagra): A preliminary report of a novel method to improve uterine artery blood flow and endometrial development in patients undergoing IVF. Hum Reprod 2000; 15(4): 806-9.
  8. Arikan DC, Bakan V, Kurutas EB, Sayar H, Coskun A. Protective effect of tadalafil on ischemia/reperfusion injury of rat ovary. J Pediatr Surg 2010; 45(11): 2203-9.
  9. Celik M, Aksoy AN, Aksoy H, Aksoy Y, Halici Z. Sildenafil reduces ischemia-reperfusion injury in rat ovary: Biochemical and histopathological evaluation. Gynecol Obstet Invest 2014; 78(3): 162-7.
  10. Fetih AN, Habib DM, Abdelaal II, Hussein M, Fetih GN, Othman ER. Adding sildenafil vaginal gel to clomiphene citrate in infertile women with prior clomiphene citrate failure due to thin endometrium: A prospective self-controlled clinical trial. Facts Views Vis Obgyn 2017; 9(1): 21-7.
  11. Lopez-Tello J, Arias-Alvarez M, Jimenez-Martinez MA, Barbero-Fernandez A, Garcia-Garcia RM, Rodriguez M, et al. The effects of sildenafil citrate on feto? placental development and haemodynamics in a rabbit model of intrauterine growth restriction. Reprod Fertil Dev 2016. [Epub ahead of print].
  12. Rashidi B, Malekzadeh M, Goodarzi M, Masoudifar A, Mirzaei H. Green tea and its anti-angiogenesis effects. Biomed Pharmacother 2017; 89: 949-56.
  13. Weis SM, Cheresh DA. Tumor angiogenesis: Molecular pathways and therapeutic targets. Nat Med 2011; 17(11): 1359-70.
  14. Petit I, Jin D, Rafii S. The SDF-1-CXCR4 signaling pathway: A molecular hub modulating neo-angiogenesis. Trends Immunol 2007; 28(7): 299-307.
  15. Caporali A, Martello A, Miscianinov V, Maselli D, Vono R, Spinetti G. Contribution of pericyte paracrine regulation of the endothelium to angiogenesis. Pharmacol Ther 2017; 171: 56-64.
  16. Tas A, Atasoy N, Ozbek H, Aslan L, Yuksel H, Dagoglu CG. Effects of sildenafil citrate (Viagra) in the early phase of healing process in open wounds induced experimentally in dogs. Acta Vet Brno 2003; 72: 273-7.
  17. Vidavalur R, Penumathsa SV, Zhan L, Thirunavukkarasu M, Maulik N. Sildenafil induces angiogenic response in human coronary arteriolar endothelial cells through the expression of thioredoxin, hemeoxygenase and vascular endothelial growth factor. Vascul Pharmacol 2006; 45(2): 91-5.
  18. Dehghani Firouzabadi R, Davar R, Hojjat F, Mahdavi M. Effect of sildenafil citrate on endometrial preparation and outcome of frozen-thawed embryo transfer cycles: A randomized clinical trial. Iran J Reprod Med 2013; 11(2): 151-8.
  19. Pyriochou A, Zhou Z, Koika V, Petrou C, Cordopatis P, Sessa WC, et al. The phosphodiesterase 5 inhibitor sildenafil stimulates angiogenesis through a protein kinase G/MAPK pathway. J Cell Physiol 2007; 211(1): 197-204.
  20. Gnainsky Y, Granot I, Aldo PB, Barash A, Or Y, Schechtman E, et al. Local injury of the endometrium induces an inflammatory response that promotes successful implantation. Fertil Steril 2010; 94(6): 2030-6.
  21. Boivin J, Bunting L, Collins JA, Nygren KG. International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care. Hum Reprod 2007; 22(6): 1506-12.
  22. Larsen U. Research on infertility: Which definition should we use? Fertil Steril 2005; 83(4): 846-52.
  23. Philippov OS, Radionchenko AA, Bolotova VP, Voronovskaya NI, Potemkina TV. Estimation of the prevalence and causes of infertility in western Siberia. Bull World Health Organ 1998; 76(2): 183-7.
  24. Safarinejad MR. Infertility among couples in a population-based study in Iran: Prevalence and associated risk factors. Int J Androl 2008; 31(3): 303-14.
  25. McWilliams GD, Frattarelli JL. Changes in measured endometrial thickness predict in vitro fertilization success. Fertil Steril 2007; 88(1): 74-81.
  26. Bulletti C, de ZD. Uterine contractility and embryo implantation. Curr Opin Obstet Gynecol 2006; 18(4): 473-84.
  27. Khairy M, Dhillon RK, Chu J, Rajkhowa M, Coomarasamy A. The effect of peri-implantation administration of uterine relaxing agents in assisted reproduction treatment cycles: a systematic review and meta-analysis. Reprod Biomed Online 2016; 32(4): 362-76.
  28. Saeedi Borujeni MJ, Hami J, Haghir H, Rastin M, Sazegar G. Evaluation of Bax and Bcl-2 proteins expression in the rat hippocampus due to childhood febrile seizure. Iran J Child Neurol 2016; 10(1): 53-60.
  29. Dekel N, Gnainsky Y, Granot I, Racicot K, Mor G. The role of inflammation for a successful implantation. Am J Reprod Immunol 2014; 72(2): 141-7.
  30. Karizbodagh MP, Rashidi B, Sahebkar A, Masoudifar A, Mirzaei H. Implantation Window and Angiogenesis. J Cell Biochem 2017; 118(12): 4141-51.
  31. Chen X, Man GCW, Liu Y, Wu F, Huang J, Li TC, et al. Physiological and pathological angiogenesis in endometrium at the time of embryo implantation. Am J Reprod Immunol 2017; 78(2).
  32. Ledee N, Petitbarat M, Chevrier L, Vitoux D, Vezmar K, Rahmati M, et al. The uterine immune profile may help women with repeated unexplained embryo implantation failure after in vitro fertilization. Am J Reprod Immunol 2016; 75(3): 388-401.
  33. Taskin MI, Yay A, Adali E, Balcioglu E, Inceboz U. Protective effects of sildenafil citrate administration on cisplatin-induced ovarian damage in rats. Gynecol Endocrinol 2015; 31(4): 272-7.
  34. Takasaki A, Tamura H, Miwa I, Taketani T, Shimamura K, Sugino N. Endometrial growth and uterine blood flow: A pilot study for improving endometrial thickness in the patients with a thin endometrium. Fertil Steril 2010; 93(6): 1851-8.
  35. Mangal S, Mehirishi S. To study and compare the effect of vaginal sildenafil and estradiol valerate on endometrial thickness, blood flow and pregnancy rates in infertile women undergoing intrauterine insemination. Int J Reprod Contracept Obstet Gynecol 2016; 5(7): 2274-7.
  36. Khan RN, Hamoud H, Warren A, Wong LF, Arulkumaran S. Relaxant action of sildenafil citrate (Viagra) on human myometrium of pregnancy. Am J Obstet Gynecol 2004; 191(1): 315-21.
  37. Farrer-Brown G, Beilby JO, Tarbit MH. The blood supply of the uterus. 1. Arterial vasculature. J Obstet Gynaecol Br Commonw 1970; 77(8): 673-81.
  38. Rashidi B, Rad JS, Rad LR. Immunohistochemical (Ki-67) study of endometrial maturation in mice after use of phosphodiesterase type 5 inhibitor. Adv Biomed Res 2015; 4: 154.
Journal of Isfahan Medical School
Volume 35, Issue 447 - Serial Number 447
July and August 2017
Pages 1217-1224

  • Receive Date 05 September 2017
  • Accept Date 06 April 2022