CC BY 4.0 · Rev Bras Ginecol Obstet 2022; 44(02): 161-168
DOI: 10.1055/s-0041-1741451
Original Article
Basic and Translational Science/In vitro fertilization

Protective Effects of Platelet-rich plasma for in vitro Fertilization of Rats with Ovarian Failure Induced by Cyclophosphamide

Efeitos protetores do plasma rico em plaquetas para fertilização in vitro de ratos com falência ovariana induzida por ciclofosfamida
1   Department of Histology and Embryology and Artificial Reproductive Techniques, Faculty of Medicine, Sakarya University, Sakarya, Turkey
,
2   Department of Obstetrics and Gynecology and Artificial Reproductive Techniques, Faculty of Medicine, Sakarya University, Sakarya, Turkey
,
3   Department of Obstetrics and Gynecology, Private Tatvan Can Hospital, Bitlis, Turkey
,
4   Department of Physiology, Faculty of Medicine, Sakarya University, Sakarya, Turkey
,
5   Specialist of Gynecological Oncology, Department of Obstetrics and Gynecology Faculty of Medicine, Sakarya University, Sakarya, Turkey
› Institutsangaben

Abstract

Objective Premature ovarian insufficiency (POI) contributes significantly to female infertility. Cyclophosphamide (CYC has adverse effects on folliculogenesis. Platelet-rich plasma (PRP) is an autologous product rich in many growth factors. We evaluated the protective effect of PRP on in vitro fertilization in female rats with CYC-induced ovarian damage.

Methods Twenty-eight adult female Sprague-Dawley rats were randomly divided into four groups. Group 1 (control-sodium chloride 0.9%; 1 mL/kg, single-dose intraperitoneal [IP] injection); group 2 (CYC), 75 mg/kg, single-dose IP injection and sodium chloride 0.9% (1 mL/kg, single-dose IP injection); group 3 CYC plus PRP, CYC (75 mg/kg, single-dose and PRP (200 μl, single-dose) IP injection); and group 4 (PRP, 200 μl, single-dose IP injection).

Results In the comparisons in terms of M1 and M2 oocytes, it was observed that the CYC group presented a significantly lower amount than the control, CYC/PRP, and PRP groups. (for M1, p = 0.000, p = 0.029, p = 0.025; for M2, p = 0.009, p = 0.004, p = 0.000, respectively). The number of fertilized oocytes and two-celled good quality embryos was found to be statistically significant between the CYC and control groups, CYC + PRP and PRP groups (p = 0.009, p = 0.001, p = 0.000 for oocytes, respectively. For embryos; p = 0.016, p = 0.002, p = 0.000).

Conclusion Platelet-rich plasma can protect the ovarian function against damage caused by CYC, and, in addition, it improves oocyte count and the development of embryos as a result of oocyte stimulation during the IVF procedure.

Resumo

Objetivo A insuficiência ovariana prematura (POI) contribui significativamente para a infertilidade feminina. A ciclofosfamida (CYC) tem efeitos adversos na foliculogênese. O plasma rico em plaquetas (PRP) é um produto autólogo rico em muitos fatores de crescimento. Avaliamos o efeito protetor do PRP na fertilização in vitro em ratas com lesão ovariana induzida por CYC.

Métodos Vinte e oito ratas Sprague-Dawley adultas foram divididas aleatoriamente em quatro grupos. Grupo 1 (controle - cloreto de sódio 0,9%; 1 mL/kg, injeção intraperitoneal [IP] em dose única); grupo 2 (CYC), 75 mg/kg, injeção IP de dose única e cloreto de sódio 0,9% (1 mL/kg, injeção ip de dose única); grupo 3 CYC + PRP, CYC (75 mg/kg, dose única e PRP (200 μl, dose única) injeção IP); e grupo 4 (PRP, 200 μl, injeção IP de dose única).

Resultados Nas comparações em termos de ovócitos M1 e M2, observou-se que o grupo CYC apresentou uma quantidade significativamente menor que os grupos controle, CYC/PRP, e PRP. (Para M1, p = 0,000, p = 0,029, p = 0,025; para M2, p = 0,009, p = 0,004, p = 0,000, respectivamente). O número de oócitos fertilizados e embriões bicelulares de boa qualidade foi considerado estatisticamente significativo entre os grupos CYC e controle, CYC + PRP e grupos PRP (p = 0,009, p = 0,001, p = 0,000 para oócitos, respectivamente. Para embriões, p = 0,016, p = 0,002, p = 0,000).

Conclusão O PRP pode proteger a função ovariana contra os danos causados pelo CYC e, além disso, proporciona melhora na contagem de oócitos e no desenvolvimento de embriões como resultado da estimulação ovariana durante o procedimento de fertilização in vitro.

Contributions

All authors contributed to the design of the study and were involved in the data collection, data analysis and/or interpretation. All authors also contributed to manuscript writing/substantive editing and review and approved the final draft of the manuscript.




Publikationsverlauf

Eingereicht: 14. Januar 2021

Angenommen: 05. Oktober 2021

Artikel online veröffentlicht:
25. Februar 2022

© 2022. Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

 
  • References

  • 1 De Vos M, Devroey P, Fauser BC. Primary ovarian insufficiency. Lancet 2010; 376 (9744): 911-921 DOI: 10.1016/S0140-6736(10)60355-8.
  • 2 Shelling AN. Premature ovarian failure. Reproduction 2010; 140 (05) 633-641 DOI: 10.1530/REP-09-0567.
  • 3 European Society for Human Reproduction and Embryology (ESHRE) Guideline Group on POI, Webber L, Davies M, Anderson R, Bartlett J, Braat D. et al; European Society for Human Reproduction and Embryology (ESHRE) Guideline Group on POI. ESHRE Guideline: management of women with premature ovarian insufficiency. Hum Reprod 2016; 31 (05) 926-937 DOI: 10.1093/humrep/dew027.
  • 4 Chae-Kim JJ, Gavrilova-Jordan L. Premature ovarian insufficiency: procreative management and preventive strategies. Biomedicines 2018; 7 (01) 2 DOI: 10.3390/biomedicines7010002.
  • 5 Christgau M, Moder D, Hiller KA, Dada A, Schmitz G, Schmalz G. Growth factors and cytokines in autologous platelet concentrate and their correlation to periodontal regeneration outcomes. J Clin Periodontol 2006; 33 (11) 837-845 DOI: 10.1111/j.1600-051X.2006.00991.x.
  • 6 Lubkowska A, Dolegowska B, Banfi G. Growth factor content in PRP and their applicability in medicine. J Biol Regul Homeost Agents 2012; 26 (02, Suppl 1): 3S-22S
  • 7 Bakacak M, Bostanci MS, İnanc F, Yaylali A, Serin S, Attar R. et al. Protective effect of platelet rich plasma on experimental ischemia/reperfusion injury in rat ovary. Gynecol Obstet Invest 2016; 81 (03) 225-231 DOI: 10.1159/000440617.
  • 8 Pintat J, Silvestre A, Magalon G, Gadeau AP, Pesquer L, Perozziello A. et al. Intra-articular injection of mesenchymal stem cells and platelet-rich plasma to treat patellofemoral osteoarthritis: preliminary results of a long-term pilot study. J Vasc Interv Radiol 2017; 28 (12) 1708-1713 DOI: 10.1016/j.jvir.2017.08.004.
  • 9 Cieslik-Bielecka A, Bielecki T, Gazdzik TS, Arendt J, Król W, Szczepanski T. Autologous platelets and leukocytes can improve healing of infected high-energy soft tissue injury. Transfus Apheresis Sci 2009; 41 (01) 9-12 DOI: 10.1016/j.transci.2009.05.006.
  • 10 Meirow D, Assad G, Dor J, Rabinovici J. The GnRH antagonist cetrorelix reduces cyclophosphamide-induced ovarian follicular destruction in mice. Hum Reprod 2004; 19 (06) 1294-1299 DOI: 10.1093/humrep/deh257.
  • 11 Soleimani R, Heytens E, Darzynkiewicz Z, Oktay K. Mechanisms of chemotherapy-induced human ovarian aging: double strand DNA breaks and microvascular compromise. Aging (Albany NY) 2011; 3 (08) 782-793 DOI: 10.18632/aging.100363.
  • 12 Dehghani F, Aboutalebi H, Esmaeilpour T, Panjehshahin MR, Bordbar H. Effect of platelet-rich plasma (PRP) on ovarian structures in cyclophosphamide-induced ovarian failure in female rats: a stereological study. Toxicol Mech Methods 2018; 28 (09) 653-659 DOI: 10.1080/15376516.2018.1491662.
  • 13 Mendes FA, Coelho Aguiar JM, Kahn SA, Reis AH, Dubois LG, Romão LF. et al. Connective-Tissue Growth Factor (CTGF/CCN2) induces astrogenesis and fibronectin expression of embryonic neural cells in vitro. PLoS One 2015; 10 (08) e0133689 DOI: 10.1371/journal.pone.0133689.
  • 14 Nagashima T, Kim J, Li Q, Lydon JP, DeMayo FJ, Lyons KM. et al. Connective tissue growth factor is required for normal follicle development and ovulation. Mol Endocrinol 2011; 25 (10) 1740-1759 DOI: 10.1210/me.2011-1045.
  • 15 McNatty KP, Juengel JL, Reader KL, Lun S, Myllymaa S, Lawrence SB. et al. Bone morphogenetic protein 15 and growth differentiation factor 9 co-operate to regulate granulosa cell function. Reproduction 2005; 129 (04) 473-480 DOI: 10.1530/rep.1.0511.
  • 16 Ozcan P, Takmaz T, Tok OE, Islek S, Yigit EN, Ficicioglu C. The protective effect of platelet-rich plasma administrated on ovarian function in female rats with Cy-induced ovarian damage. J Assist Reprod Genet 2020; 37 (04) 865-873 DOI: 10.1007/s10815-020-01689-7.
  • 17 van Kasteren Y. Treatment concepts for premature ovarian failure. J Soc Gynecol Investig 2001; 8 (1, Suppl Proceedings) S58-S59
  • 18 Cakiroglu Y, Saltik A, Yuceturk A, Karaosmanoglu O, Kopuk SY, Scott RT. et al. Effects of intraovarian injection of autologous platelet rich plasma on ovarian reserve and IVF outcome parameters in women with primary ovarian insufficiency. Aging (Albany NY) 2020; 12 (11) 10211-10222 DOI: 10.18632/aging.103403.
  • 19 Hino C, Ueda J, Funakoshi H, Matsumoto S. Defined oocyte collection time is critical for reproducible in vitro fertilization in rats of different strains. Theriogenology 2020; 144: 146-151 DOI: 10.1016/j.theriogenology.2020.01.006.
  • 20 Agca Y, Critser JK. Chapter 7 - Assisted reproductive technologies and genetic modifications in rats. In: Suckow MA, Weisbroth SH, Franklin CL. eds. The laboratory rat. 2nd ed. Burlington: Academic Press; 2006: 165-189
  • 21 Seed J, Chapin RE, Clegg ED, Dostal LA, Foote RH, Hurtt ME. et al; ILSI Risk Science Institute Expert Working Group on Sperm Evaluation. Methods for assessing sperm motility, morphology, and counts in the rat, rabbit, and dog: a consensus report. Reprod Toxicol 1996; 10 (03) 237-244 DOI: 10.1016/0890-6238(96)00028-7.
  • 22 Sirard MA, Florman HM, Leibfried-Rutledge ML, Barnes FL, Sims ML, First NL. Timing of nuclear progression and protein synthesis necessary for meiotic maturation of bovine oocytes. Biol Reprod 1989; 40 (06) 1257-1263 DOI: 10.1095/biolreprod40.6.1257.
  • 23 Ebrahimi M, Akbari Asbagh F. Pathogenesis and causes of premature ovarian failure: an update. Int J Fertil Steril 2011; 5 (02) 54-65
  • 24 Blumenfeld Z. Premature ovarian failure: etiology and possible prevention. Expert Rev Endocrinol Metab 2009; 4 (02) 173-181 DOI: 10.1586/17446651.4.2.173.
  • 25 Liu T, Huang Y, Zhang J, Qin W, Chi H, Chen J. et al. Transplantation of human menstrual blood stem cells to treat premature ovarian failure in mouse model. Stem Cells Dev 2014; 23 (13) 1548-1557 DOI: 10.1089/scd.2013.0371.
  • 26 Sun M, Wang S, Li Y, Yu L, Gu F, Wang C. et al. Adipose-derived stem cells improved mouse ovary function after chemotherapy-induced ovary failure. Stem Cell Res Ther 2013; 4 (04) 80 DOI: 10.1186/scrt231.
  • 27 Schmitz JP, Hollinger JO. The biology of platelet-rich plasma. J Oral Maxillofac Surg 2001; 59 (09) 1119-1121 DOI: 10.1053/joms.2001.26801.
  • 28 Borrione P, Gianfrancesco AD, Pereira MT, Pigozzi F. Platelet-rich plasma in muscle healing. Am J Phys Med Rehabil 2010; 89 (10) 854-861 DOI: 10.1097/PHM.0b013e3181f1c1c7.
  • 29 Foster TE, Puskas BL, Mandelbaum BR, Gerhardt MB, Rodeo SA. Platelet-rich plasma: from basic science to clinical applications. Am J Sports Med 2009; 37 (11) 2259-2272 DOI: 10.1177/0363546509349921.
  • 30 Comish PB, Drumond AL, Kinnell HL, Anderson RA, Matin A, Meistrich ML. et al. Fetal cyclophosphamide exposure induces testicular cancer and reduced spermatogenesis and ovarian follicle numbers in mice. PLoS One 2014; 9 (04) e93311 DOI: 10.1371/journal.pone.0093311.
  • 31 Liu HZ, Tao YX, Luo P, Deng CM, Gu YP, Yang L. et al. Preventive effects of a novel polysaccharide from sepia esculenta ink on ovarian failure and its action mechanisms in cyclophosphamide-treated mice. J Agric Food Chem 2016; 64 (28) 5759-5766 DOI: 10.1021/acs.jafc.6b01854.
  • 32 Roness H, Kashi O, Meirow D. Prevention of chemotherapy-induced ovarian damage. Fertil Steril 2016; 105 (01) 20-29 DOI: 10.1016/j.fertnstert.2015.11.043.
  • 33 Uhm SJ, Gupta MK, Yang JH, Chung HJ, Min TS, Lee HT. Epidermal growth factor can be used in lieu of follicle-stimulating hormone for nuclear maturation of porcine oocytes in vitro. Theriogenology 2010; 73 (08) 1024-1036 DOI: 10.1016/j.theriogenology.2009.11.029.
  • 34 Maleki-Hajiagha A, Razavi M, Rouholamin S, Rezaeinejad M, Maroufizadeh S, Sepidarkish M. Intrauterine infusion of autologous platelet-rich plasma in women undergoing assisted reproduction: A systematic review and meta-analysis. J Reprod Immunol 2020; 137: 103078 DOI: 10.1016/j.jri.2019.103078.
  • 35 Molina A, Sánchez J, Sánchez W, Vielma V. Platelet-rich plasma as an adjuvant in the endometrial preparation of patients with refractory endometrium. JBRA Assist Reprod 2018; 22 (01) 42-48 DOI: 10.5935/1518-0557.20180009.
  • 36 Callejo J, Salvador C, González-Nuñez S, Almeida L, Rodriguez L, Marqués L. et al. Live birth in a woman without ovaries after autograft of frozen-thawed ovarian tissue combined with growth factors. J Ovarian Res 2013; 6 (01) 33 DOI: 10.1186/1757-2215-6-33.
  • 37 Sfakianoudis K, Simopoulou M, Nitsos N, Rapani A, Pantou A, Vaxevanoglou T. et al. A case series on platelet-rich plasma revolutionary management of poor responder patients. Gynecol Obstet Invest 2019; 84 (01) 99-106 DOI: 10.1159/000491697.
  • 38 Stojkovska S, Dimitrov G, Stamenkovska N, Hadzi-Lega M, Petanovski Z. Live birth rates in poor responders' group after previous treatment with autologous platelet-rich plasma and low dose ovarian stimulation compared with poor responders used only low dose ovarian stimulation before in vitro fertilization. Open Access Maced J Med Sci 2019; 7 (19) 3184-3188 DOI: 10.3889/oamjms.2019.825.
  • 39 Fabi S, Sundaram H. The potential of topical and injectable growth factors and cytokines for skin rejuvenation. Facial Plast Surg 2014; 30 (02) 157-171 DOI: 10.1055/s-0034-1372423.
  • 40 Herraiz S, Buigues A, Díaz-García C, Romeu M, Martínez S, Gómez-Seguí I. et al. Fertility rescue and ovarian follicle growth promotion by bone marrow stem cell infusion. Fertil Steril 2018; 109 (05) 908-918.e2 DOI: 10.1016/j.fertnstert.2018.01.004.
  • 41 Durlinger AL, Gruijters MJ, Kramer P, Karels B, Kumar TR, Matzuk MM. et al. Anti-Müllerian hormone attenuates the effects of FSH on follicle development in the mouse ovary. Endocrinology 2001; 142 (11) 4891-4899 DOI: 10.1210/endo.142.11.8486.