Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

The Influence of Platelet-Derived Growth Factors on the Proliferation of Germinal Epithelium After Local Irradiation with Electrons

Authors
Demyashkin Grigory A 1
Vadyukhin Matvey A 2
Shekin Vladimir I 2
1 I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; A. Tsyb Medical Radiological Research Centre, Ministry of Health of Russian Federation, Obninsk, Russia
2 I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
10.18502/jri.v24i2.12494
Abstract
Background: At present, the damage of male reproductive function caused by electron irradiation, as well as the development of methods for its correction are the relevant topics for further research. In fact, the effect of leukocyte-poor platelet-rich plasma (LP-PRP) growth factors are poorly investigated on different aspects of male fertility. Methods: In this study, Wistar rats were divided into four groups; I) control which were injected with saline; II and III) groups (n=65) whose testes were locally irradiated with electrons to a dose of 2 Gy (linear accelerator "NOVAC-11"); III) the group (n=30) which received LP-PRP for 11 weeks after irradiation; and IV)‌ animals (n=30) which received only LP-PRP (conditional control). The testes were studied by histological, immunohistochemical (IHC), western blotting, and TUNEL methods using Ki-67, Bcl-2, and p53. Comparison between groups was performed and p<0.01 was set as the level of significance. Results: The results showed a decrease in the expression levels of Ki-67 and Bcl-2 besides an increase in p53-positive cells by the end of the experiment (p<0.01). After injection of LP-PRP, a gradual restoration of the proliferative activity of gametes was noted, which was confirmed by an increase in the proportion of Ki-67- and Bcl-2-positive germ cells (46.4±2.3, p<0.01 and 23.5±1.1, respectively, p<0.01). Conclusion: Ki-67 expression and TUNEL analysis in the testes revealed a modulation of the proliferative-apoptotic balance towards apoptosis of germ cells after 2 Gy local electron irradiation. A tendency to restore the proliferative-apoptotic balance was noted after LP-PRP injections as indicated by increase in Ki-67-positive germ cells.
Keywords
Cell cycle
Electrons
Growth Factors
Infertility
platelet
Rich Plasma
spermatogenesis
Vander Borght M, Wyns C. Fertility and infertility: definition and epidemiology. Clin Biochem. 2018; 62:2-10.
Meistrich ML. Effects of chemotherapy and radiotherapy on spermatogenesis in humans. Fertil Steril. 2013;100(5):1180-6.
Sineath RC, Mehta A. Preservation of fertility in testis cancer management. Urol Clin North Am. 2019;46(3):341-51.
Qu N, Itoh M, Sakabe K. Effects of chemotherapy and radiotherapy on spermatogenesis: the role of testicular immunology. Int J Mol Sci.2019;20(4):957.
Abd El Tawab AM, Shahin NN, AbdelMohsen MM. Protective effect of Satureja montana extract on cyclophosphamide-induced testicular injury in rats. Chem Biol Interact. 2014;224:196-205.
Everts P, Onishi K, Jayaram P, Lana JF, Mautner K. Platelet-rich plasma: new performance understandings and therapeutic considerations in 2020. Int J Mol Sci. 2020;21(20):7794.
Garcia K, Wichmann A, Su TT. Cell cycle regulation. Fly (Austin). 2007;1(2):125-31.
Dehghani F, Sotoude N, Bordbar H, Panjeshahin MR, Karbalay-Doust S. The use of platelet-rich plasma (PRP) to improve structural impairment of rat testis induced by busulfan. Platelets. 2019;30 (4):513-20.
Guo M, Hay BA. Cell proliferation and apoptosis. Curr Opin Cell Biol. 1999;11(6):745-52.
Zhao WP, Wang HW, Liu J, Tan PP, Luo XL, Zhu SQ, et al. Positive PCNA and Ki-67 expression in the testis correlates with spermatogenesis dysfunction in fluoride-treated rats. Biol Trace Elem Res. 2018;186(2):489-97.
Bagheri H, Salajegheh A, Javadi A, Amini P, Shekarchi B, Shabeeb D, et al. Radioprotective effects of zinc and selenium on mice spermatogenesis. J Biomed Phys Eng. 2020;10(6):707-12.
Wang Q, Zhou Y, Wang X, Evers BM. Glycogen synthase kinase-3 is a negative regulator of extracellular signal-regulated kinase. Oncogene. 2006;25(1):43-50.
Morel C, Carlson SM, White FM, Davis RJ. Mcl-1 integrates the opposing actions of signaling pathways that mediate survival and apoptosis. Mol Cell Biol. 2009;29(14):3845-52.
Reisz JA, Bansal N, Qian J, Zhao W, Furdui CM. Effects of ionizing radiation on biological molecules--mechanisms of damage and emerging methods of detection. Antioxid Redox Signal. 2014;21 (2):260-92.
Demyashkin GA, Borovaya TG, Andreeva YY, Nedorubov AA, Stepanova YY, Vadyukhin MA, et al. An experimental approach to comprehend the influence of platelet rich growth factors on spermatogenesis. Int J Radiat Biol. 2022;98(8):1330-43.
Maria-Angeliki G, Alexandros-Efstratios K, Dimitris R, Konstantinos K. Platelet-rich plasma as a potential treatment for noncicatricial alopecias. Int J Trichology. 2015;7(2):54-63.
Kutluhan MA, Özsoy E, Şahin A, Ürkmez A, Topaktaş R, Toprak T, et al. Effects of platelet-rich plasma on spermatogenesis and hormone production in an experimental testicular torsion model. Andrology. 2021;9(1):407-13.
Vergara SP, Lizama C, Brouwer-Visser J, Moreno RD. Expression of BCL-2 family genes in germ cells undergoing apoptosis during the first wave of spermatogenesis in the rat. Andrologia. 2011;43 (4):242-7.
Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, et al. Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. Cell Death Differ. 2018;25(3):486-541.
Journal of Reproduction & Infertility
Volume 24, Issue 2
Spring 2023
Pages 94-100