Research Article
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Year 2024, Volume: 41 Issue: 1, 160 - 165, 29.03.2024

Oğuzhan Kuşcu Fikret Altındağ Rahmi Aslan Murat Çetin Rağbetli

Abstract

References

  • Aygün D, Kaplan S, Odaci E, Onger ME, Altunkaynak ME. Toxicity of non-steroidal anti-inflammatory drugs: a review of melatonin and diclofenac sodium association. Histol Histopathol 2012;27:417–436.
  • Antonucci R, Zaffanello M, Puxeddu E, Porcella A, Cuzzolin L, Pilloni MD, Fanos . Use of non-steroidal anti-inflammatory drugs in pregnancy: impact on the fetus and newborn, Curr Drug Metab 2012;13:474–490.
  • Özbudak H, Ünal AZ, Sabuncuoğlu S. Gebelikte Non-Steroidal Antiinflamatuvar İlaçların Kullanımın Değerlendirilmesi. Marmara Pharm J 2016;20:64–71.
  • Bailey J, Knight A, Balcombe J. The Future of Teratology research is in vitro. Biogenic Amines 2005;19:97–145.
  • Rossitto M, Marchive C, Pruvost A, Sellem E, Ghettas A, Badiou S, Sutra T, Poulat F, Philibert P, Boizet-Bonhoure B. Intergenerational effects on mouse sperm quality after in utero exposure to acetaminophen and ibuprofen. FASEB J 2019;33:339–357.
  • Stanfield KM, Khan KN. Localization of COX-2 in the male reproductive tract during sexual maturation. Inflammopharmacology 2003;11:259–266.
  • Cheuk BL, Leung PS, Lo AC, Wong PY. Androgen control of cyclooxygenase expression in the rat epididymis. Biol Reprod 2000;63:775–780.
  • Ragbetli MC, Ozyurt B, Aslan H, Odaci E, Gokcimen A, Sahin B, Kaplan S. Effect of prenatal exposure to diclofenac sodium on Purkinje cell numbers in rat cerebellum: a stereological study. Brain Res 2007;1174:130–135.
  • F. Gevrek, M. Kara, M.Ç. Rağbetli, H. Aslan, Effects of prenatally exposed diclofenac sodium on rat heart tissue: a stereological and histological study, Turk J Med Sci. 45 (2015) 474–480.
  • Altındağ F, Rağbetli MÇ. The effect of maternal treatment with diclofenac sodium and thymoquinone on testicular parameters in rat offspring. Rev Int Androl 2021;19:34–40.
  • Mülazımoğlu SB, İde T, Aslan S. Ratlarda Üreme JCAM 2012:39–44.
  • Altındağ F, Özdek U. Synergistic effects of sinapic acid and ellagic acid ameliorate streptozotocin-induced diabetic nephropathy by inhibiting apoptosis, DNA damage, and structural deterioration in rats. Hum Exp Toxicol 2021;40:290–299.
  • Ayengin K, Alp HH, Huyut Z, Yıldırım S, Altındag F, Avci V. The effects of CoQ10 supplement on matrix metalloproteinases, oxidative DNA damage and pro-inflammatory cytokines in testicular ischaemia/reperfusion injury in rats. Andrologia 2021;53:e13839.
  • Mayhew TM, Gundersen HJ. If you assume, you can make an ass out of u and me: a decade of the disector for stereological counting of particles in 3D space. J Anat 1996;188:1–15.
  • Zhu X, Yao Y, Yang J, Zhengxie J, Li X, Hu S, Zhang A, Dong J, Zhang C, Gan G. COX-2-PGE2 signaling pathway contributes to hippocampal neuronal injury and cognitive impairment in PTZ-kindled epilepsy mice. Int Immunopharmacol 2020;87:106801.
  • Neeraja S, Sreenath AS, Reddy R, Reddanna P. Expression of cyclooxygenase-2 in rat testis. Reprod Biomed Online 2003;6:302–309.
  • McKanna JA, Zhang MZ, Wang JL, Cheng H, Harris RC. Constitutive expression of cyclooxygenase-2 in rat vas deferens. Am J Physiol 1998;275:R227–R233.
  • Wong PY, Chan HC, Leung PS, Chung YW, Wong YL, Lee WM, Ng V, Dun NJ. Regulation of anion secretion by cyclo-oxygenase and prostanoids in cultured epididymal epithelia from the rat. J Physiol 1999;514;809–820.
  • Lazarus M, Munday CJ, Eguchi N, Matsumoto S, Killian GJ, Kubata BK, Urade Y. Immunohistochemical localization of microsomal PGE synthase-1 and cyclooxygenases in male mouse reproductive organs. Endocrinology 2002;143:2410–2419.
  • Fouchécourt S, Métayer S, Locatelli A, Dacheux F, Dacheux JL. Stallion epididymal fluid proteome: qualitative and quantitative characterization; secretion and dynamic changes of major proteins. Biol Reprod 2000;62:1790–1803.
  • Schell C, Frungieri MB, Albrecht M, Gonzalez-Calvar MI, Köhn FM, Calandra RS, Mayerhofer A. prostaglandin D2 system in the human testis. Fertil Steril 2007;88:233–236.
  • Ibtisham F, Chen J, Niu N, Wang Z, Wu J, Xiao M, An L. Effect of Aspirin on Reproductive Profile of Male Rat An-Overview. IJSR 2016;5: 5–12.
  • Gravel A, Wilson JM, Pedro DF, Vijayan MM. Non-steroidal anti-inflammatory drugs disturb the osmoregulatory, metabolic and cortisol responses associated with seawater exposure in rainbow trout. Comp Biochem Physiol C Toxicol Pharmacol 2009;149:481–490.
  • Ben Maamar M, Lesné L, Hennig K, Desdoits-Lethimonier C, KilcoyneCKR, Coiffec I, Rolland AD, Chevrier C, Kristensen DM, Lavoué V, Antignac JP, Le Bizec B, Dejucq-Rainsford N, Mitchell RT, Mazaud-Guittot S, Jégou B. Ibuprofen results in alterations of human fetal testis development. Sci Rep 2017;7:44184.
  • Balin PDS, Jorge BC, Leite ARR, Borges CS, Oba E, Silva EJR, de Barros AL, Horta-Júnior JAC, Arena AC. Maternal exposure to ibuprofen can affect the programming of the hypothalamus of the male offspring. Regul Toxicol Pharmacol 2020;111:104576.
  • Kristensen DM, Hass U, Lesné L, Lottrup G, Jacobsen PR, Desdoits-Lethimonier C, Boberg J, Petersen JH, Toppari J, Jensen TK, Brunak S, Skakkebaek NE, Nellemann C, Main KM, Jégou B, Leffers H. Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat. Hum Reprod 2011;26:235–244.
  • Ji K, LiuX, Lee S, Kang S, Kho Y, Giesy JP, Choi K. Effects of non-steroidal anti-inflammatory drugs on hormones and genes of the hypothalamic-pituitary-gonad axis, and reproduction of zebrafish. J Hazard Mater 2013; 254–255 :242–251.
  • Adeyemi WJ, Omoniyi JA, Olayiwola A, Ibrahim M, Ogunyemi O, Olayaki LA. Elevated reproductive toxicity effects of diclofenac after withdrawal: Investigation of the therapeutic role of melatonin. Toxicol Rep 2019;6:571–577.
  • Kristensen DM, Desdoits-Lethimonier C, Mackey AL, Dalgaard MD, De Masi F, Munkbøl CH, Styrishave B, Antignac JP, Le Bizec B, Platel C, Hay-Schmidt A, Jensen TK, Lesné L, Mazaud-Guittot S, Kristiansen K, Brunak S, Kjaer M, Juul A, Jégou B. Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism. Proc Natl Acad Sci U S A 2018;115:E715–E724.
  • Niu X, de Graaf IA, van der Bij HA, Groothuis GM. Precision cut intestinal slices are an appropriate ex vivo model to study NSAID-induced intestinal toxicity in rats. Toxicol In Vitro 2014;28:1296–1305.
  • Robaire B, Hinton BT, Orgebin-Crist MC. The epididymis, In Knobil and Neill's physiology of reproduction. New York: Elsevier 2006:1071–1148.
  • Turner TT. De Graaf's thread: the human epididymis. J Androl 2008;29:237–250.
  • Haidl G, Duan YG, Chen SJ, Kohn FM, Schuppe HC, Allam JP. The role of mast cells in male infertility. Expert Rev Clin Immunol 2011;7:627–634.
  • Zhang P, Wang ZL, Yang ZH, Su XJ, Wang XH. A novel rat model of seminal vesiculitis. Asian J Androl 2019;21:360–364.
  • Seshadri S, Bates M, Vince G, Jones DI. Cytokine expression in the seminal plasma and its effects on fertilisation rates in an IVF cycle. Andrologia 2011;43:378–386.

Effects of diclofenac sodium exposure during pregnancy on COX-2 expression in the ductus epididymis and ductus deferens of the offspring rat

Year 2024, Volume: 41 Issue: 1, 160 - 165, 29.03.2024

Oğuzhan Kuşcu Fikret Altındağ Rahmi Aslan Murat Çetin Rağbetli

Abstract

The present study aimed to investigate the effects of diclofenac sodium application during pregnancy on COX-2 expression in the ductus epididymis (DE) and ductus deferens (DD) of the offspring rat. 8 adult Wistar Albino non-pregnant female rats and two breeding male rats were utilized. Rats determined to be pregnant were separated into two categories as sham (S) and diclofenac sodium (DS). It was injected into the S group with 1 ml/kg/day saline for 10 days, and it was injected into the DS group with 6.1 mg/kg/day DS. 7 male offspring were used in each group. DS decreased the serum testosterone levels and incresed the number of mast. DS induced fibrotic thickening. Offspring of S group had moderate COX-2 in the caput epididymis (CPE) and severe COX-2 in the cauda epididymis (CE), while those in the DS group had weak COX-2 in the CPE and moderate COX-2 in the CE. There was no COX-2 expression in the vas deferens and corpus epididymis (COE) of the offspring rats in the S and DS groups. TNF-α expression was not observed in the S and DS groups. It was observed that moderate IL-10 expression in the CPE and CE, and weak IL-10 expression in the vas deferens and COE in the S and DS groups. The findings of our study reveal that DS administration during pregnancy can cause the downregulation of COX-2 expression in the DE and DD of offspring rats and therefore may have adverse effects on the male reproductive system.

Keywords

COX-2 Diclofenac sodium Ductus epididymis Rat Vas deferens.

References

  • Aygün D, Kaplan S, Odaci E, Onger ME, Altunkaynak ME. Toxicity of non-steroidal anti-inflammatory drugs: a review of melatonin and diclofenac sodium association. Histol Histopathol 2012;27:417–436.
  • Antonucci R, Zaffanello M, Puxeddu E, Porcella A, Cuzzolin L, Pilloni MD, Fanos . Use of non-steroidal anti-inflammatory drugs in pregnancy: impact on the fetus and newborn, Curr Drug Metab 2012;13:474–490.
  • Özbudak H, Ünal AZ, Sabuncuoğlu S. Gebelikte Non-Steroidal Antiinflamatuvar İlaçların Kullanımın Değerlendirilmesi. Marmara Pharm J 2016;20:64–71.
  • Bailey J, Knight A, Balcombe J. The Future of Teratology research is in vitro. Biogenic Amines 2005;19:97–145.
  • Rossitto M, Marchive C, Pruvost A, Sellem E, Ghettas A, Badiou S, Sutra T, Poulat F, Philibert P, Boizet-Bonhoure B. Intergenerational effects on mouse sperm quality after in utero exposure to acetaminophen and ibuprofen. FASEB J 2019;33:339–357.
  • Stanfield KM, Khan KN. Localization of COX-2 in the male reproductive tract during sexual maturation. Inflammopharmacology 2003;11:259–266.
  • Cheuk BL, Leung PS, Lo AC, Wong PY. Androgen control of cyclooxygenase expression in the rat epididymis. Biol Reprod 2000;63:775–780.
  • Ragbetli MC, Ozyurt B, Aslan H, Odaci E, Gokcimen A, Sahin B, Kaplan S. Effect of prenatal exposure to diclofenac sodium on Purkinje cell numbers in rat cerebellum: a stereological study. Brain Res 2007;1174:130–135.
  • F. Gevrek, M. Kara, M.Ç. Rağbetli, H. Aslan, Effects of prenatally exposed diclofenac sodium on rat heart tissue: a stereological and histological study, Turk J Med Sci. 45 (2015) 474–480.
  • Altındağ F, Rağbetli MÇ. The effect of maternal treatment with diclofenac sodium and thymoquinone on testicular parameters in rat offspring. Rev Int Androl 2021;19:34–40.
  • Mülazımoğlu SB, İde T, Aslan S. Ratlarda Üreme JCAM 2012:39–44.
  • Altındağ F, Özdek U. Synergistic effects of sinapic acid and ellagic acid ameliorate streptozotocin-induced diabetic nephropathy by inhibiting apoptosis, DNA damage, and structural deterioration in rats. Hum Exp Toxicol 2021;40:290–299.
  • Ayengin K, Alp HH, Huyut Z, Yıldırım S, Altındag F, Avci V. The effects of CoQ10 supplement on matrix metalloproteinases, oxidative DNA damage and pro-inflammatory cytokines in testicular ischaemia/reperfusion injury in rats. Andrologia 2021;53:e13839.
  • Mayhew TM, Gundersen HJ. If you assume, you can make an ass out of u and me: a decade of the disector for stereological counting of particles in 3D space. J Anat 1996;188:1–15.
  • Zhu X, Yao Y, Yang J, Zhengxie J, Li X, Hu S, Zhang A, Dong J, Zhang C, Gan G. COX-2-PGE2 signaling pathway contributes to hippocampal neuronal injury and cognitive impairment in PTZ-kindled epilepsy mice. Int Immunopharmacol 2020;87:106801.
  • Neeraja S, Sreenath AS, Reddy R, Reddanna P. Expression of cyclooxygenase-2 in rat testis. Reprod Biomed Online 2003;6:302–309.
  • McKanna JA, Zhang MZ, Wang JL, Cheng H, Harris RC. Constitutive expression of cyclooxygenase-2 in rat vas deferens. Am J Physiol 1998;275:R227–R233.
  • Wong PY, Chan HC, Leung PS, Chung YW, Wong YL, Lee WM, Ng V, Dun NJ. Regulation of anion secretion by cyclo-oxygenase and prostanoids in cultured epididymal epithelia from the rat. J Physiol 1999;514;809–820.
  • Lazarus M, Munday CJ, Eguchi N, Matsumoto S, Killian GJ, Kubata BK, Urade Y. Immunohistochemical localization of microsomal PGE synthase-1 and cyclooxygenases in male mouse reproductive organs. Endocrinology 2002;143:2410–2419.
  • Fouchécourt S, Métayer S, Locatelli A, Dacheux F, Dacheux JL. Stallion epididymal fluid proteome: qualitative and quantitative characterization; secretion and dynamic changes of major proteins. Biol Reprod 2000;62:1790–1803.
  • Schell C, Frungieri MB, Albrecht M, Gonzalez-Calvar MI, Köhn FM, Calandra RS, Mayerhofer A. prostaglandin D2 system in the human testis. Fertil Steril 2007;88:233–236.
  • Ibtisham F, Chen J, Niu N, Wang Z, Wu J, Xiao M, An L. Effect of Aspirin on Reproductive Profile of Male Rat An-Overview. IJSR 2016;5: 5–12.
  • Gravel A, Wilson JM, Pedro DF, Vijayan MM. Non-steroidal anti-inflammatory drugs disturb the osmoregulatory, metabolic and cortisol responses associated with seawater exposure in rainbow trout. Comp Biochem Physiol C Toxicol Pharmacol 2009;149:481–490.
  • Ben Maamar M, Lesné L, Hennig K, Desdoits-Lethimonier C, KilcoyneCKR, Coiffec I, Rolland AD, Chevrier C, Kristensen DM, Lavoué V, Antignac JP, Le Bizec B, Dejucq-Rainsford N, Mitchell RT, Mazaud-Guittot S, Jégou B. Ibuprofen results in alterations of human fetal testis development. Sci Rep 2017;7:44184.
  • Balin PDS, Jorge BC, Leite ARR, Borges CS, Oba E, Silva EJR, de Barros AL, Horta-Júnior JAC, Arena AC. Maternal exposure to ibuprofen can affect the programming of the hypothalamus of the male offspring. Regul Toxicol Pharmacol 2020;111:104576.
  • Kristensen DM, Hass U, Lesné L, Lottrup G, Jacobsen PR, Desdoits-Lethimonier C, Boberg J, Petersen JH, Toppari J, Jensen TK, Brunak S, Skakkebaek NE, Nellemann C, Main KM, Jégou B, Leffers H. Intrauterine exposure to mild analgesics is a risk factor for development of male reproductive disorders in human and rat. Hum Reprod 2011;26:235–244.
  • Ji K, LiuX, Lee S, Kang S, Kho Y, Giesy JP, Choi K. Effects of non-steroidal anti-inflammatory drugs on hormones and genes of the hypothalamic-pituitary-gonad axis, and reproduction of zebrafish. J Hazard Mater 2013; 254–255 :242–251.
  • Adeyemi WJ, Omoniyi JA, Olayiwola A, Ibrahim M, Ogunyemi O, Olayaki LA. Elevated reproductive toxicity effects of diclofenac after withdrawal: Investigation of the therapeutic role of melatonin. Toxicol Rep 2019;6:571–577.
  • Kristensen DM, Desdoits-Lethimonier C, Mackey AL, Dalgaard MD, De Masi F, Munkbøl CH, Styrishave B, Antignac JP, Le Bizec B, Platel C, Hay-Schmidt A, Jensen TK, Lesné L, Mazaud-Guittot S, Kristiansen K, Brunak S, Kjaer M, Juul A, Jégou B. Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism. Proc Natl Acad Sci U S A 2018;115:E715–E724.
  • Niu X, de Graaf IA, van der Bij HA, Groothuis GM. Precision cut intestinal slices are an appropriate ex vivo model to study NSAID-induced intestinal toxicity in rats. Toxicol In Vitro 2014;28:1296–1305.
  • Robaire B, Hinton BT, Orgebin-Crist MC. The epididymis, In Knobil and Neill's physiology of reproduction. New York: Elsevier 2006:1071–1148.
  • Turner TT. De Graaf's thread: the human epididymis. J Androl 2008;29:237–250.
  • Haidl G, Duan YG, Chen SJ, Kohn FM, Schuppe HC, Allam JP. The role of mast cells in male infertility. Expert Rev Clin Immunol 2011;7:627–634.
  • Zhang P, Wang ZL, Yang ZH, Su XJ, Wang XH. A novel rat model of seminal vesiculitis. Asian J Androl 2019;21:360–364.
  • Seshadri S, Bates M, Vince G, Jones DI. Cytokine expression in the seminal plasma and its effects on fertilisation rates in an IVF cycle. Andrologia 2011;43:378–386.
There are 35 citations in total.

Details

Primary Language English
Subjects Histology and Embryology
Journal Section Research Article
Authors

Oğuzhan Kuşcu 0000-0003-0150-1715

Fikret Altındağ 0000-0002-4074-5168

Rahmi Aslan 0000-0002-4563-0386

Murat Çetin Rağbetli 0000-0002-8189-264X

Publication Date March 29, 2024
Submission Date February 22, 2024
Acceptance Date March 21, 2024
Published in Issue Year 2024 Volume: 41 Issue: 1

Cite

APA Kuşcu, O., Altındağ, F., Aslan, R., Rağbetli, M. Ç. (2024). Effects of diclofenac sodium exposure during pregnancy on COX-2 expression in the ductus epididymis and ductus deferens of the offspring rat. Journal of Experimental and Clinical Medicine, 41(1), 160-165.
AMA Kuşcu O, Altındağ F, Aslan R, Rağbetli MÇ. Effects of diclofenac sodium exposure during pregnancy on COX-2 expression in the ductus epididymis and ductus deferens of the offspring rat. J. Exp. Clin. Med. March 2024;41(1):160-165.
Chicago Kuşcu, Oğuzhan, Fikret Altındağ, Rahmi Aslan, and Murat Çetin Rağbetli. “Effects of Diclofenac Sodium Exposure During Pregnancy on COX-2 Expression in the Ductus Epididymis and Ductus Deferens of the Offspring Rat”. Journal of Experimental and Clinical Medicine 41, no. 1 (March 2024): 160-65.
EndNote Kuşcu O, Altındağ F, Aslan R, Rağbetli MÇ (March 1, 2024) Effects of diclofenac sodium exposure during pregnancy on COX-2 expression in the ductus epididymis and ductus deferens of the offspring rat. Journal of Experimental and Clinical Medicine 41 1 160–165.
IEEE O. Kuşcu, F. Altındağ, R. Aslan, and M. Ç. Rağbetli, “Effects of diclofenac sodium exposure during pregnancy on COX-2 expression in the ductus epididymis and ductus deferens of the offspring rat”, J. Exp. Clin. Med., vol. 41, no. 1, pp. 160–165, 2024.
ISNAD Kuşcu, Oğuzhan et al. “Effects of Diclofenac Sodium Exposure During Pregnancy on COX-2 Expression in the Ductus Epididymis and Ductus Deferens of the Offspring Rat”. Journal of Experimental and Clinical Medicine 41/1 (March 2024), 160-165.
JAMA Kuşcu O, Altındağ F, Aslan R, Rağbetli MÇ. Effects of diclofenac sodium exposure during pregnancy on COX-2 expression in the ductus epididymis and ductus deferens of the offspring rat. J. Exp. Clin. Med. 2024;41:160–165.
MLA Kuşcu, Oğuzhan et al. “Effects of Diclofenac Sodium Exposure During Pregnancy on COX-2 Expression in the Ductus Epididymis and Ductus Deferens of the Offspring Rat”. Journal of Experimental and Clinical Medicine, vol. 41, no. 1, 2024, pp. 160-5.
Vancouver Kuşcu O, Altındağ F, Aslan R, Rağbetli MÇ. Effects of diclofenac sodium exposure during pregnancy on COX-2 expression in the ductus epididymis and ductus deferens of the offspring rat. J. Exp. Clin. Med. 2024;41(1):160-5.
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