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Kastamonu Medical Journal

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Original Article
Immunohistochemical investigation of the effects of different doses of some endocrine-disrupting chemicals on receptorinteracting serine/threonine-protein kinase 1 (RIPK1) levels in the testis
Abstract
Aims: The reproductive toxicity of endocrine-disrupting chemicals (EDCs) is well known, but the underlying mechanism remains unclear. Receptor-interacting serine/threonine protein kinase 1 (RIPK1) mainly mediates cell death and inflammation. It is crucial to both necroptosis and apoptosis. Therefore, in this study, we aimed to investigate the changes in RIPK1 expression levels immunohistochemically in the adverse mechanism of EDCs on spermatogenic cells.
Methods: Forty-two Wistar Albino male rats (10 weeks old, 250±50 g) were assigned into seven groups. Bisphenol A (BPA), 4-Nonylphenol (NP), and their mixtures at low 25 mg/kg doses and high 100 mg/kg doses were used. The control group received corn oil via gastric tube. At the end of the 21 days of the experimental protocol, the testis tissues were extracted and immersed in Bouin's solution. Five µm sections were taken from the tissue and stained immunohistochemically with an anti-RIPK1 antibody. Histo (H)-score was calculated by determining the intensity of immunoreactivity in the sections.
Results: The results showed that the mixed dose group and all high-dose group round spermatids had excessive RIPK1 immunoreactivities compared to the control group and individually low-dose group of both (p<0.01). This result might be responsible for poor sperm quality, motility disruptions, or other reproductive consequences.
Conclusion: In conclusion, RIPK1 overactivation may be essential in pathophysiological conditions caused by EDC exposure at high doses and their mixture. Further studies are now needed to evaluate RIPK1 overactivation in testis tissues.

Keywords : Apoptosis, endocrine-disrupting chemicals, necroptosis, RIPK1

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1. Amaro AA, Esposito AI, Mirisola V, et al. Endocrine disruptor agentnonyl phenol exerts an estrogen-like transcriptional activity on estrogenreceptor positive breast cancer cells. Curr Med Chem. 2014;21(5):630-640.doi:10.2174/09298673113209990169
2. Bai N, Abuduaini R, Wang S, Zhang M, Zhu X, Zhao Y. Nonylphenolbiodegradation characterizations and bacterial composition analysis of aneffective consortium NP-M2. Environ Pollut. Jan 2017;220(Pt A):95-104.doi:10.1016/j.envpol.2016.09.027
3. Brouard V, Drouault M, Elie N, et al. Effects of bisphenol A and estradiolin adult rat testis after prepubertal and pubertal exposure. Reprod Toxicol.2022;111:211-224. doi:10.1016/j.reprotox.2022.06.004
4. Li X, Ying GG, Su HC, Yang XB, Wang L. Simultaneous determinationand assessment of 4-nonylphenol, bisphenol A and triclosan in tap water,bottled water and baby bottles. Environ Int. Aug 2010;36(6):557-562.doi:10.1016/j.envint.2010.04.009
5. Acir IH, Guenther K. Endocrine-disrupting metabolites of alkylphenolethoxylates - A critical review of analytical methods, environmentaloccurrences, toxicity, and regulation. Sci Total Environ. 2018;635:1530-1546. doi:10.1016/j.scitotenv.2018.04.079
6. Soares A, Guieysse B, Jefferson B, Cartmell E, Lester JN. Nonylphenolin the environment: a critical review on occurrence, fate, toxicity andtreatment in wastewaters. Environ Int. 2008;34(7):1033-49. doi:10.1016/j.envint.2008.01.004
7. Ijaz MU, Tahir A, Samad A, Anwar H. Nobiletin ameliorates nonylphenol-induced testicular damage by improving biochemical, steroidogenic,hormonal, spermatogenic, apoptotic and histological profile. Hum ExpToxicol. 2021;40(3):403-416. doi:10.1177/0960327120950007
8. Ma Y, Liu H, Wu J, et al. The adverse health effects of bisphenol A andrelated toxicity mechanisms. Environ Res. 2019;176:108575. doi:10.1016/j.envres.2019.108575
9. Minguez-Alarcon L, Gaskins AJ, Chiu YH, et al. Urinary bisphenol Aconcentrations and association with in vitro fertilization outcomes amongwomen from a fertility clinic. Hum Reprod. Sep 2015;30(9):2120-2028.doi:10.1093/humrep/dev183
10. Tarafdar A, Sirohi R, Balakumaran PA, et al. The hazardous threat ofBisphenol A: Toxicity, detection and remediation. J Hazard Mater.2022;423(Pt A):127097. doi:10.1016/j.jhazmat.2021.127097
11. Olukole SG, Lanipekun DO, Ola-Davies EO, Oke BO. Melatonin attenuatesbisphenol A-induced toxicity of the adrenal gland of Wistar rats. EnvironSci Pollut Res Int. 2019;26(6):5971-5982. doi:10.1007/s11356-018-4024-5
12. Nakamura D, Yanagiba Y, Duan Z, et al. Bisphenol A may cause testosteronereduction by adversely affecting both testis and pituitary systemssimilar to estradiol. Toxicol Lett. 2010;194(1-2):16-25. doi:10.1016/j.toxlet.2010.02.002
13. Kazemi S, Bahramifar N, Moghadamnia AA, Jorsarae SG. Detection ofbisphenol a and nonylphenol in rat&rsquo;s blood serum, tissue and impacton reproductive system. Electron Physician. 2016;8(8):2772-2780.doi:10.19082/2772
14. Li YJ, Song TB, Cai YY, et al. Bisphenol A exposure induces apoptosis andupregulation of Fas/FasL and caspase-3 expression in the testes of mice.Toxicol Sci. 2009;108(2):427-36. doi:10.1093/toxsci/kfp024
15. Li D, Meng L, Xu T, et al. RIPK1-RIPK3-MLKL-dependent necrosispromotes the aging of mouse male reproductive system. Elife.2017;6:e27692. doi:10.7554/eLife.27692
16. Melebary SJ, AlGhamdi MS, Elhalwagy MEA, Alsolmy SA, Bin DohaishAJA. Disturbance in some fertility biomarkers induced and changesin testis architecture by chronic exposure to various dosages of each ofnonylphenol or bisphenol a and their mix. Life (Basel). 2022;12(10):1555.doi:10.3390/life12101555
17. Tatar M, Tufekci KK, Uslu S, &Ouml;ner J. Expression of ADAMTS 1-4-8 andplacental growth factor in ovary and oviduct during pregnancy in thefirst trimester. Anat Histol Embryol. 2023;52(4):619-626. doi:10.1111/ahe.12922
18. Tufekci KK, Bakirhan EG, Terzi F. A maternal high-fat diet causes anxiety-related behaviors by altering neuropeptide y1 receptor and hippocampalvolumes in rat offspring: the potential effect of n-acetylcysteine.Mol Neurobiol. 2023;60(3):1499-1514. doi:10.1007/s12035-022-03158-x
19. Toyama Y, Suzuki-Toyota F, Maekawa M, Ito C, Toshimori K. Adverseeffects of bisphenol A to spermiogenesis in mice and rats. Arch HistolCytol. 2004;67(4):373-381. doi:10.1679/aohc.67.373
20. Zhang J, Liu J, Ren L, et al. PM(2.5) induces male reproductive toxicity viamitochondrial dysfunction, DNA damage and RIPK1 mediated apoptoticsignaling pathway. Sci Total Environ. 2018;634:1435-1444. doi:10.1016/j.scitotenv.2018.03.383
21. Ying F, Ding C, Ge R, et al. Comparative evaluation of nonylphenol isomerson steroidogenesis of rat Leydig Cells. Toxicol In Vitro. 2012;26(7):1114-1121. doi:10.1016/j.tiv.2012.06.016
22. Salian S, Doshi T, Vanage G. Impairment in protein expression profile oftesticular steroid receptor coregulators in male rat offspring perinatallyexposed to Bisphenol A. Life Sci. 2009;85(1-2):11-18. doi:10.1016/j.lfs.2009.04.005
23. Al-Griw MA, Alghazeer RO, Salama NM, et al. Paternal bisphenol Aexposure induces testis and sperm pathologies in mice offspring: Possiblydue to oxidative stress? Saudi J Biol Sci. 2021;28(1):948-955. doi:10.1016/j.sjbs.2020.11.003
24. Kalb AC, Kalb AL, Cardoso TF, et al. Maternal transfer of bisphenol aduring nursing causes sperm impairment in male offspring. Arch EnvironContam Toxicol. 2016;70(4):793-801. doi:10.1007/s00244-015-0199-7
25. Vijaykumar T, Singh D, Vanage GR, Dhumal RV, Dighe VD. BisphenolA-induced ultrastructural changes in the testes of common marmoset.Indian J Med Res. Jul 2017;146(1):126-137. doi:10.4103/ijmr.IJMR_927_15
26. Ayazgok B, Tuylu Kucukkilinc T. Low-dose bisphenol A induces RIPK1-mediated necroptosis in SH-SY5Y cells: Effects on TNF-alpha andacetylcholinesterase. J Biochem Mol Toxicol. 2018:e22233. doi:10.1002/jbt.22233
27. Sun TC, Li DM, Yu H, et al. Bilateral varicocele leads to ferroptosis,pyroptosis and necroptosis of human spermatozoa and affects semenquality in infertile men. Front Cell Dev Biol. 2023;11:1091438. doi:10.3389/fcell.2023.1091438
28. Yuan L, Liang P, Qu Y, et al. Protective effect of astaxanthin against SnS(2)nanoflowers induced testes toxicity by suppressing RIPK1-RIPK3-MLKLsignaling in mice. Food Chem Toxicol. Nov 2020;145:111736. doi:10.1016/j.fct.2020.111736
29. Moriwaki K, Chan FK. Regulation of RIPK3- and RHIM-dependentNecroptosis by the Proteasome. J Biol Chem. 2016;291(11):5948-5959.doi:10.1074/jbc.M115.700997
Article available in :
Volume 3, Issue 3, 2023
Page : 165-169
https://doi.org/10.51271/KMJ-0119
Article Information
Received : 22 Ağu 2023
Accepted : 11 Eyl 2023
Published : 22 Eyl 2023
Corresponding Author :

Kıymet Kübra Tüfekci: Kastamonu University, Faculty of Medicine, Histology and Embryology Department

[email protected]
Citation : Tüfekci KK. Immunohistochemical investigation of the effects of different doses of some endocrine-disrupting chemicals on receptor- interacting serine/threonine-protein kinase 1 (RIPK1) levels in the testis. Kastamonu Med J. 2023;3(3):165-169.

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