Volume 26, Issue 1 (1-2022)                   ibj 2022, 26(1): 44-52 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Kondratska O, Grushka N, Pavlovych S, Krasutska N, Tsyhankov S, Yanchii R. Effects of Poly (ADP-ribose) Polymerase Inhibition on DNA Integrity and Gene Expression in Ovarian Follicular Cells in Mice with Endotoxemia. ibj. 2022; 26 (1) :44-52
URL: http://ibj.pasteur.ac.ir/article-1-3493-en.html
Background: A mouse model of lipopolysaccharide (LPS)-induced inflammation was used to investigate the effect of pharmacological inhibition of nuclear enzyme PARP-1 on oocyte maturation, apoptotic and necrotic death, as well as DNA integrity of follicular cells. Also, the relative expression of cumulus genes (HAS2, COX2, and GREM1) associated with oocyte developmental competence was assessed. Methods: Mice were treated with the PARP-1 inhibitor, 4-HQN, one hour before LPS administration. After 24 h, oocyte in vitro maturation was detected. Granulosa cell DNA damage was determined by the alkaline comet assay. Live, necrotic and apoptotic cells were identified using double vital staining by fluorescent dyes, Hoechst 33342 and propidium iodide. The expression levels of cumulus genes were assessed using reverse transcriptase PCR. Results: The administration of 4-HQN to LPS-treated mice ameliorated oocyte meiotic maturation and exerted a significant cytoprotective effect. 4-HQN attenuated LPS-induced DNA damage and favored cell survival by decreasing necrosis and apoptosis in granulosa cells. Exposure to 4-HQN increased mRNA expression levels for HAS2, COX2, and GREM1 in cumulus cells. Conclusion: The obtained results indicate the involvement of PARP-1 in the pathogenesis of ovarian dysfunction caused by LPS. We suppose that this enzyme can be an attractive target for the therapy of inflammatory disorders in ovary. The protective action of PARP-1 inhibition could at least partly be associated with the reduction of necrotic death of follicular cells and also in other cells. However, the detailed mechanisms of the favorable effect of PARP inhibitors on endotoxin-induced ovarian disorders need to be further explored.
Type of Study: Full Length | Subject: Related Fields

1. Bidne KL, Dickson MJ, Ross JW, Baumgard LH, Keating AF. Disruption of female reproductive function by endotoxins. Reproduction 2018; 155(4): R169-R181. [DOI:10.1530/REP-17-0406]
2. Shepel E, Grushka N, Makogon N, Sribna V,
3. Pavlovych S, Yanchii R. Changes in DNA integrity and gene expression in ovarian follicular cells
4. of lipopolysaccharide-treated female mice. Pharmacological reports 2018; 70(6): 1146-1149. [DOI:10.1016/j.pharep.2018.06.005]
5. Shimizu T, Watanabe K, Anayama N, Miyazaki K. Effect of lipopolysaccharide on circadian clock genes Per2 and Bmal1 in mouse ovary. The journal of physiological sciences 2017; 67(5): 623-628. [DOI:10.1007/s12576-017-0532-1]
6. Shimizu T, Miyauchi K, Shirasuna K, Bollwein H, Magata F, Murayama C, Miyamoto A. Effects of lipopolysaccharide (LPS) and peptidoglycan (PGN) on estradiol production in bovine granulosa cells from small and large follicles. Toxicology in vitro 2012; 26(7): 1134-1142. [DOI:10.1016/j.tiv.2012.06.014]
7. Magata F, Horiuchi M, Miyamoto A, Shimizu T. Lipopolysaccharide (LPS) inhibits steroid production in theca cells of bovine follicles in vitro: distinct effect of LPS on theca cell function in pre- and post-selection follicles. The journal of reproduction and development 2014; 60(4): 280-287. [DOI:10.1262/jrd.2013-124]
8. Magata F, Shimizu T. Effect of lipopolysaccharide on developmental competence of oocytes. Reproductive toxicology 2017; 71: 1-7. [DOI:10.1016/j.reprotox.2017.04.001]
9. Zhao SJ, Pang YW, Zhao XM, Du WH, Hao HS, Zhu HB. Effects of lipopolysaccharide on maturation of bovine oocyte in vitro and its possible mechanisms. Oncotarget 2017; 8(3): 4656-4667. [DOI:10.18632/oncotarget.13965]
10. Tremellen K, Syedi N, Tan S, Pearce K. Metabolic endotoxaemia-a potential novel link between ovarian inflammation and impaired progesterone production. Gynecological endocrinology 2015; 31(4): 309-312. [DOI:10.3109/09513590.2014.994602]
11. Wang G, Huang X, Li Y, Guo K, Ning P, Zhang Y. PARP-1 inhibitor, DPQ, attenuates LPS-induced acute lung injury through inhibiting NF-κB-mediated inflammatory response. PloS one 2013; 8(11): e79757. [DOI:10.1371/journal.pone.0079757]
12. Sethi GS, Dharwal V, Naura AS. Poly(ADP-ribose) polymerase-1 in lung inflammatory disorders: a review. Frontiers in immunology 2017; 8: 1172. [DOI:10.3389/fimmu.2017.01172]
13. Pazzaglia S, Pioli C. Multifaceted role of PARP-1 in DNA repair and inflammation: pathological and therapeutic implications in cancer and non-cancer diseases. Cells 2019; 9(1): 41. [DOI:10.3390/cells9010041]
14. Ba X, Garg NJ. Signaling mechanism of poly(ADP-ribose) polymerase-1 (PARP-1) in inflammatory diseases. The American journal of pathology 2011; 178(3): 946-955. [DOI:10.1016/j.ajpath.2010.12.004]
15. Makogon N, Voznesenskaya T, Bryzgina T, Sukhina V, Grushka N, Alexeyeva I. Poly(ADP-ribose) polymerase inhibitor, 3-aminobenzamide, protects against experimental immune ovarian failure in mice. Reproductive biology 2010; 10(3): 215-226. [DOI:10.1016/S1642-431X(12)60041-2]
16. Jog NR, Dinnall JA, Gallucci S, Madaio MP, Caricchio R. Poly(ADP-ribose) polymerase-1 regulates the progression of autoimmune nephritis in males by inducing necrotic cell death and modulating inflammation. Journal of immunology 2009; 182(11): 7297-7306. [DOI:10.4049/jimmunol.0803565]
17. Gonzalez-Rey E, Martínez-Romero R, O'Valle F, Aguilar-Quesada R, Conde C, Delgado M, Oliver FJ. Therapeutic effect of a poly(ADP-ribose) polymerase-1 inhibitor on experimental arthritis by downregulating inflammation and Th1 response. PloS one 2007; 2(10): e1071. [DOI:10.1371/journal.pone.0001071]
18. Fehr AR, Singh SA, Kerr CM, Mukai S, Higashi H, Aikawa M. The impact of PARPs and ADP-ribosylation on inflammation and host-pathogen interactions. Genes and development 2020; 34(5-6): 341-359. [DOI:10.1101/gad.334425.119]
19. García S, Conde C. The role of poly(ADP-ribose) polymerase-1 in rheumatoid arthritis. Mediators of inflammation 2015; 2015: 837250. [DOI:10.1155/2015/837250]
20. Szabo C, Martins V, Liaudet L. Poly(ADP-ribose) polymerase inhibition in acute lung injury. A reemerging concept. American journal of respiratory cell and molecular biology 2020; 63(5): 571-590. [DOI:10.1165/rcmb.2020-0188TR]
21. Veres B, Radnai B, Gallyas F Jr, Varbiro G, Berente Z, Osz E, Sumegi B. Regulation of kinase cascades and transcription factors by a poly(ADP-ribose) polymerase-1 inhibitor, 4-hydroxyquinazoline, in lipopoly-saccharide-induced inflammation in mice. The journal of pharmacology and experimental therapeutics 2004; 310(1): 247-255. [DOI:10.1124/jpet.104.065151]
22. Shimizu S, Eguchi Y, Kamiike W, Akao Y, Kosaka H, Hasegawa J, Matsuda H, Tsujimoto Y. Involvement of ICE family proteases in apoptosis induced by reoxygenation of hypoxic hepatocytes. The American journal of physiology 1996; 271(6 Pt 1): G949-958. [DOI:10.1152/ajpgi.1996.271.6.G949]
23. Collins AR. The comet assay for DNA damage and repair: principles, applications, and limitations. Molecular biotechnology 2004; 26(3): 249-261. [DOI:10.1385/MB:26:3:249]
24. Alvarado Rincón JA, Gindri PC, Mion B, Giuliana de Ávila F, Barbosa AA, Maffi AS, Pradieé J, Mondadori RG, Corrêa MN, Ligia Margareth Cantarelli P, Schneider A. Early embryonic development of bovine oocytes challenged with LPS in vitro or in vivo. Reproduction 2019; 158(5): 453-463. [DOI:10.1530/REP-19-0316]
25. Wang G, Huang X, Li Y, Guo K, Ning P, Zhang Y. PARP-1 inhibitor, DPQ, attenuates LPS-induced acute lung injury through inhibiting NF-κB-mediated inflammatory response. PloS one 2013; 8(11): e79757. [DOI:10.1371/journal.pone.0079757]
26. Brady PN, Goel A, Johnson MA. Poly(ADP-ribose) polymerases in host-pathogen interactions, inflammation, and immunity. Microbiology and molecular biology reviews. 2018; 83(1): e00038-18. [DOI:10.1128/MMBR.00038-18]
27. Sriram CS, Jangra A, Gurjar SS, Hussain MI, Borah P, Lahkar M, Mohan P, Bezbaruah BK. Poly (ADP-ribose) polymerase-1 inhibitor, 3-aminobenzamide pretreatment ameliorates lipopolysaccharide-induced neurobehavioral and neurochemical anomalies in mice. Pharmacology, biochemistry, and behavior 2015; 133: 83-91. [DOI:10.1016/j.pbb.2015.03.022]
28. Zhang JN, Ma Y, Wei XY, Liu KY, Wang H, Han H, Cui Y, Zhang MX, Qin WD. Remifentanil protects against lipopolysaccharide-induced inflammation through PARP-1/NF-κB signaling pathway. Mediators of inflammation 2019; 2019: 3013716. [DOI:10.1155/2019/3013716]
29. Grushka N, Pavlovych S, Kondratska O, Pilkevich N, Yanchii R. The effect of poly(ADP-ribose) polymerase inhibition on morpho-functional state of immunocytes under the condition of experimental endotoxemia in mice. World journal of pharmacy and pharmaceutical sciences 2019; 8(8): 161-173.
30. Henning RJ, Bourgeois M, Harbison RD. Poly(ADP-ribose) polymerase (PARP) and PARP inhibitors: mechanisms of action and role in cardiovascular disorders. Cardiovascular toxicology 2018; 18(6): 493-506. [DOI:10.1007/s12012-018-9462-2]
31. Wardi J, Ernst O, Lilja A, Aeed H, Katz S, Ben-Nachum I, Ben-Dror I, Katz D, Bernadsky O, Kandhikonda R, Avni Y, Fraser IDC, Weinstain R, Biro A, Zor T. 3-Aminobenzamide prevents concanavalin A-induced acute hepatitis by an anti-inflammatory and anti-oxidative mechanism. Digestive diseases and sciences 2018; 63(12): 3382-3397. [DOI:10.1007/s10620-018-5267-1]
32. Dhali A, Javvaji PK, Kolte AP, Francis JR, Roy SC, Sejian V. Temporal expression of cumulus cell marker genes during in vitro maturation and oocyte developmental competence. Journal of assisted reproduction and genetics 2017;34(11): 1493-1500. [DOI:10.1007/s10815-017-0998-z]
33. McKenzie LJ, Pangas SA, Carson SA, Kovanci E, Cisneros P, Buster JE, Amato P, Matzuk MM. Human cumulus granulosa cell gene expression: a predictor of fertilization and embryo selection in women undergoing IVF. Human reproduction 2004; 19(12): 2869-2874. [DOI:10.1093/humrep/deh535]
34. Scarica C, Cimadomo D, Dovere L. Giancani A, Stoppa M, Capalbo A, Ubaldi FM, Rienzi L, Canipari R. An integrated investigation of oocyte developmental competence: expression of key genes in human cumulus cells, morphokinetics of early divisions, blastulation, and euploidy. Journal of assisted reproduction and genetics 2019; 36(5): 875-887. [DOI:10.1007/s10815-019-01410-3]
35. Cillo F, Brevini TA, Antonini S, Paffoni A, Ragni G, Gandolfi F. Association between human oocyte developmental competence and expression levels of some cumulus genes. Reproduction 2007; 134(5): 645-650. [DOI:10.1530/REP-07-0182]
36. Anderson RA, Sciorio R, Kinnell H, Bayne RA, Thong KJ, de Sousa PA, Pickering S. Cumulus gene expression as a predictor of human oocyte fertilisation, embryo development and competence to establish a pregnancy. Reproduction 2009; 138(4): 629-637. [DOI:10.1530/REP-09-0144]
37. Gebhardt KM, Feil DK, Dunning KR, Lane M, Russell DL. Human cumulus cell gene expression as a biomarker of pregnancy outcome after single embryo transfer. Fertility and sterility 2011; 96(1): 47-52. [DOI:10.1016/j.fertnstert.2011.04.033]
38. Ezzati M, Roshangar L, Soleimani Rad J, Karimian N. Evaluating the effect of melatonin on HAS2, and PGR expression, as well as cumulus expansion, and fertility potential in mice. Cell journal 2018; 20(1): 108-112.
39. Boruszewska D, Kowalczyk-Zieba I, Suwik K, Staszkiewicz-Chodor J, Jaworska J, Lukaszuk K, Woclawek-Potocka I. Prostaglandin E2 affects in vitro maturation of bovine oocytes. Reproductive biology and endocrinology 2020; 18(1): 40. [DOI:10.1186/s12958-020-00598-9]
40. Kim T, Kim Y, Lucien F, Zhao Y, Enninga EA. Decreased gremlin 1 expression in women with body mass index ≥35 kg/m2 is mediated by interleukin 10 and interleukin 1β in the follicular fluid. F and S science 2020; 1(1): 16-26. [DOI:10.1016/j.xfss.2020.06.003]
41. Bhardwaj R, Ansari MM, Pandey S, Parmar MS, Chandra V, Kumar GS, Sharma GT. GREM1, EGFR, and HAS2; the oocyte competence markers for improved buffalo embryo production in vitro. Theriogenology 2016; 86(8): 2004-2011. [DOI:10.1016/j.theriogenology.2016.06.019]
42. Sun X, Xiu F, Pan B, Li Y, Haskins JT, Shen W, Li J. Antimicrobial peptide expression in swine granulosa cells in response to lipopolysaccharide. Theriogenology 2018; 119: 80-90. [DOI:10.1016/j.theriogenology.2018.06.011]
43. Piersanti RL, Santos JEP, Sheldon IM, Bromfield JJ. Lipopolysaccharide and tumor necrosis factor-alpha alter gene expression of oocytes and cumulus cells during bovine in vitro maturation. Molecular reproduction and development 2019; 86(12): 1909-1920. [DOI:10.1002/mrd.23288]
44. Kapoor K, Singla E, Sahu B, Naura AS. PARP inhibitor, olaparib ameliorates acute lung and kidney injury upon intratracheal administration of LPS in mice. Molecular and cellular biochemistry 2015; 400(1-2): 153-162. [DOI:10.1007/s11010-014-2271-4]
45. Shepel E, Grushka N, Makogon N, Voznesenskaya T, Yanchii R. Inhibition of poly (ADP-ribose) polymerase (PARP) protects against experimental immune complex-induced ovarian failure in mice. International journal of health sciences and research 2016; 6(11): 103-108.

Add your comments about this article : Your username or Email:

Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2022 CC BY-NC 4.0 | Iranian Biomedical Journal

Designed & Developed by : Yektaweb