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Lutein modulates transcription dysregulation of adhesion molecules and spermatogenesis transcription factors induced by testicular ischemia reperfusion injury: it could be SAFE

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Abstract

Testicular ischemia reperfusion injury (tIRI) is considered as the underlying mechanism of testicular torsion, which can cause male infertility. tIRI-induced damage was investigated by assessing the gene expression of spermatogenesis master transcription factors (TFs) and that of major adhesion molecules of the blood-testis barrier. The effect of lutein, a hydroxyl carotenoid, in alleviating tIRI-induced damage was also studied. Male Sprague-Dawley rats were divided into three groups: sham, unilateral tIRI, and tIRI + lutein (0.2 mg/kg). tIRI was induced by occlusion of the testicular artery for 1 h, followed by 4 h of reperfusion. Lutein was injected 15 min after the start of ischemia. Histological analysis and real-time polymerase chain reaction revealed significant decreases in tissue biopsy scores, reduced seminiferous tubule diameters, and downregulated the mRNA expression of the TFs cAMP-responsive element modulator (CREM), TATA box-binding protein-related factor 2 (TRF2), and regulatory factor X 2 (RFX2) compared with the sham group. Lutein treatment reversed these effects. The mRNA expression of the adhesion molecules N-cadherin, nectin-2, claudin-11, occludin, and connexin-43 was significantly downregulated during tIRI, but this change was prevented by lutein treatment. In addition, lutein normalized the tIRI-induced increase in total antioxidant capacity, increased malondialdehyde (MDA) levels, augmented number of TdT-mediated dUTP-X nick-end labeling (TUNEL)-positive nuclei, and activated caspase-8 pathway. The components of survivor activating factor enhancement (SAFE) were also activated during tIRI. Increased tissue expression of TNF-α and its receptor, TNFR1, was accompanied by increased phosphorylation of Janus kinase (JAK) and STAT3, which was prevented by lutein treatment. Our findings suggested that tIRI-induced spermatogenic damage may involve modulation of the SAFE pathway and could benefit from lutein treatment.

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References

  • Aktaş BK, Bulut S, Bulut S, Baykam MM, Ozden C, Senes M, Yücel D, Memiş A (2010) The effects of N-acetylcysteine on testicular damage in experimental testicular ischemia/reperfusion injury. Pediatr Surg Int 26:293–298

    Article  PubMed  Google Scholar 

  • Al-Maghrebi M, Kehinde EO, Anim JT (2010) Long term testicular ischemia-reperfusion injury-induced apoptosis: involvement of survivin down-regulation. Biochem Biophys Res Commun 395:342–347

    Article  CAS  PubMed  Google Scholar 

  • Al-Maghrebi M, Renno WM, Al-Ajmi N (2012) Epigallocatechin-3-gallate inhibits apoptosis and protects testicular seminiferous tubules from ischemia/reperfusion-induced inflammation. Biochem Biophys Res Commun 420:434–439

    Article  CAS  PubMed  Google Scholar 

  • Almeida J, Conley AJ, Ball BA (2013) Expression of anti-Müllerian hormone, CDKN1B, connexin 43, androgen receptor and steroidogenic enzymes in the equine cryptorchid testis. Equine Vet J 45:538–545

    Article  CAS  PubMed  Google Scholar 

  • Altavilla D, Romeo C, Squadrito F (2012) Molecular pathways involved in the early and late damage induced by testis ischemia: evidence for a rational pharmacological modulation. Curr Med Chem 19:1219–1224

    Article  CAS  PubMed  Google Scholar 

  • Andersson A-M, Edvardsen K, Skakkebaek NE (1994) Expression and localization of N- and E-cadherin in the human testis and epididymis. Int J Androl 17:174–180

    Article  CAS  PubMed  Google Scholar 

  • Batias C, Siffroi JP, Fenichel P, Pointis G, Segretain D (2000) Connexin43 gene expression and regulation in the rodent seminiferous epithelium. J Histochem Cytochem 48:793–805

    Article  CAS  PubMed  Google Scholar 

  • Blank ML, O’Neill PO, Steigman CK, Cobb LM, Wilde RA, Havenstein PJ, Chaudry IH (1993) Reperfusion injury following testicular torsion and detorsion in prepubertal rats. Urol Res 21:389–393

    Article  CAS  PubMed  Google Scholar 

  • Bouchard MJ, Dong Y, McDermott BM Jr, Lam DH, Brown KR, Shelanski M, Bellvé AR, Racaniello VR (2000) Defects in nuclear and cytoskeletal morphology and mitochondrial localization in spermatozoa of mice lacking nectin-2, a component of cell-cell adherens junctions. Mol Cell Biol 20:2865–2873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Byers SW, Jegou B, MacCalman C, Blaschuk OW (1993) Sertoli cell adhesion molecules and the collective organization of the testis. In: Russell LD, Griswold MD (eds) The Sertoli cell. Cache River, Clearwater, FL, pp 461–476

    Google Scholar 

  • Carette D, Weider K, Gilleron J, Giese S, Dompierre J, Bergmann M, Brehm R, Denizot JP, Segretain D, Pointis G (2010) Major involvement of connexin 43 in seminiferous epithelial junction dynamics and male fertility. Dev Biol 346:54–67

    Article  CAS  PubMed  Google Scholar 

  • Cheng CY, Mruk DD (2009) An intracellular trafficking pathway in the seminiferous epithelium regulating spermatogenesis: a biochemical and molecular perspective. Crit Rev Biochem Mol Biol 44:245–263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chew BP, Park JS (2004) Carotenoid action on the immune response. J Nutr 134:257S–261S

    CAS  PubMed  Google Scholar 

  • Chiba K, Kondo Y, Yamaguchi K, Miyake H, Fujisawa M (2012) Inhibition of claudin-11 and occludin expression in rat Sertoli cells by mono-(2-ethylhexyl) phthalate through p44/42 mitogen-activated protein kinase pathway. J Androl 33:368–374

    Article  CAS  PubMed  Google Scholar 

  • Contuk G, Orun O, Demiralp-Ekşioğlu E, Ercan F (2012) Morphological alterations and distribution of occludin in rat testes after bilateral vasectomy. Acta Histochem 114:244–251

    Article  CAS  PubMed  Google Scholar 

  • Defamie N, Berthaut I, Mograbi B, Chevallier D, Dadoune JP, Fenichel P, Segretain D, Pointis G (2003) Impaired gap junction connexin43 in Sertoli cells of patients with secretory azoospermia: a marker of undifferentiated Sertoli cells. Lab Invest 83:449–456

    Article  CAS  PubMed  Google Scholar 

  • Derycke LD, Bracke ME (2004) N-cadherin in the spotlight of cell cell adhesion, differentiation, embryogenesis, invasion and signalling. Int J Dev Biol 48:463–476

    Article  CAS  PubMed  Google Scholar 

  • Deuchar GA, Opie LH, Lecour S (2007) TNFalpha is required to confer protection in an in vivo model of classical ischaemic preconditioning. Life Sci 80:1686–1691

    Article  CAS  PubMed  Google Scholar 

  • Fernandez-Sevilla JM, Fernandez FGA, Grima EM (2010) Biotechnological production of lutein and its applications. Appl Micro Biotechnol 86:27–40

    Article  CAS  Google Scholar 

  • Filho DW, Torres MA, Bordin AL, Crezcynski-Pasa TB, Boveris A (2004) Spermatic cord torsion, reactive oxygen and nitrogen species and ischemia-reperfusion injury. Mol Aspects Med 25:199–210

    Article  PubMed  Google Scholar 

  • Fimia GM, Morlon A, Macho B, De Cesare D, Sassone-Corsi P (2001) Transcriptional cascades during spermatogenesis: pivotal role of CREM and ACT. Mol Cell Endocrinol 179:17–23

    Article  CAS  PubMed  Google Scholar 

  • Foulkes NS, Mellstrom B, Benusiglio E et al (1992) Developmental switch of CREM function during spermatogenesis: from antagonist to activator. Nature 355:80–84

    Article  CAS  PubMed  Google Scholar 

  • Gerber J, Weider K, Hambruch N, Brehm R (2014) Loss of connexin43 (Cx43) in Sertoli cells leads to spatio-temporal alterations in occludin expression. Histol Histopathol 29:935–94

    CAS  PubMed  Google Scholar 

  • Goodwin LO, Karabinus DS, Pergolizzi RG (2000) Presence of N-cadherin transcripts in mature spermatozoa. Mol Hum Reprod 6:487–497

    Article  CAS  PubMed  Google Scholar 

  • Gow A, Southwood CM, Li JS, Pariali M, Riordan GP, Brodie SE, Danias J, Bronstein JM, Kachar B, Lazzarini RA (1999) CNS myelin and Sertoli cell tight junction strands are absent in Osp/claudin-11 null mice. Cell 99:649–659

    Article  CAS  PubMed  Google Scholar 

  • Hales DB, Diemer T, Hales KH (1999) Role of cytokines in testicular function. Endocrine 10:201–217

    Article  CAS  PubMed  Google Scholar 

  • Hao WY, Shao CH, Feng YL, Hu JT, Li Q, Wang HQ, Wang PT (2013) Hypoxia reduces the proliferation and occludin expression of primary sertoli cells. Zhonghua Nan Ke Xue 19:29–34

    CAS  PubMed  Google Scholar 

  • Harikumar KB, Nimita CV, Preethi KC, Kuttan R, Shankaranarayana ML, Deshpande J (2008) Toxicity profile of lutein and lutein ester isolated from marigold flowers (Tagetes erecta). Int J Toxicol 27:1–9

    Article  CAS  PubMed  Google Scholar 

  • Haverfield JT, Meachem SJ, O'Bryan MK, McLachlan RI, Stanton PG (2013) Claudin-11 and connexin-43 display altered spatial patterns of organization in men with primary seminiferous tubule failure compared with controls. Fertil Steril 100:658–666

    Article  CAS  PubMed  Google Scholar 

  • Hermo L, Pelletier RM, Cyr DG, Smith CE (2010) Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 4: intercellular bridges, mitochondria, nuclear envelope, apoptosis, ubiquitination, membrane/voltage-gated channels, methylation/acetylation, and transcription factors. Microsc Res Tech 73:364–408

    CAS  PubMed  Google Scholar 

  • Johnsen SG (1970) Testicular biopsy score count—a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormones 1:2–2

    Article  CAS  PubMed  Google Scholar 

  • Johnston DS, Wright WW, Dicandeloro P, Wilson E, Kopf GS, Jelinsky SA (2008) Stage-specific gene expression is a fundamental characteristic of rat spermatogenic cells and Sertoli cells. Proc Natl Acad Sci U S A 105:8315–8320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karaguzel E, Kadihasanoglu M, Kutlu O (2014) Mechanisms of testicular torsion and potential protective agents. Nat Rev Urol 11:391–399

    Article  CAS  PubMed  Google Scholar 

  • Kijlstra A, Tian Y, Kelly ER, Berendschot TT (2012) Lutein: more than just a filter for blue light. Prog Retin Eye Res 31:303–315

    Article  CAS  PubMed  Google Scholar 

  • Kim JH, Na HJ, Kim CK, Kim JY, Ha KS, Lee H, Chung HT, Kwon HJ, Kwon YG, Kim YM (2008) The non-provitarnin A carotenoid, lutein, inhibits NF-kappa B-dependent gene expression through redox-based regulation of the phosphatidylinositol 3-kinase/PTEN/Akt and NF-kappa B-inducing kinase pathways: role of H2O2 in NF-kappa B activation. Free Radic Biol Med 45:885–896

    Article  CAS  PubMed  Google Scholar 

  • Kimmins S, Kotaja N, Davidson I, Sassone-Corsi P (2004) Testis-specific transcription mechanisms promoting male germ-cell differentiation. Reproduction 128:5–12

    Article  CAS  PubMed  Google Scholar 

  • Kistler WS, Baas D, Lemeille S, Paschaki M, Seguin-Estevez Q, Barras E, Ma W, Duteyrat JL, Morlé L, Durand B, Reith W (2015) RFX2 is a major transcriptional regulator of spermiogenesis. PLoS Genet 11:e1005368–1005396

    Article  PubMed  PubMed Central  Google Scholar 

  • Krinsky NI, Landrum JT, Bone RA (2003) Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye. Annu Rev Nutr 23:171–201

    Article  CAS  PubMed  Google Scholar 

  • Lachance C, Leclerc P (2011) Mediators of the Jak/STAT signaling pathway in human spermatozoa. Biol Reprod 85:1222–12231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lachance C, Goupil S, Leclerc P (2013) Stattic V, a STAT3 inhibitor, affects human spermatozoa through regulation of mitochondrial activity. J Cell Physiol 228:704–713

    Article  CAS  PubMed  Google Scholar 

  • Lecour S, Suleman N, Deuchar GA, Somers S, Lacerda L, Huisamen B, Opie LH (2005) Pharmacological preconditioning with tumor necrosis factor-alpha activates signal transducer and activator of transcription-3 at reperfusion without involving classic prosurvival kinases (Akt and extracellular signal-regulated kinase). Circulation 112:3911–3918

    Article  CAS  PubMed  Google Scholar 

  • Lecour S (2009) Multiple protective pathways against reperfusion injury: a SAFE path without Aktion? J Mol Cell Cardiol 46:607–609

    Article  CAS  PubMed  Google Scholar 

  • Li SY, Fu ZJ, Ma H, Jang WC, So KF, Wong D, Lo ACY (2009) Effect of lutein on retinal neurons and oxidative stress in a model of acute retinal ischemia/reperfusion. Invest Ophthalmol Vis Sci 50:836–843

    Article  PubMed  Google Scholar 

  • Li SY, Yang D, Fu ZJ, Woo T, Wong D, Lo AC (2012) Lutein enhances survival and reduces neuronal damage in a mouse model of ischemic stroke. Neurobiol Dis 45:624–632

    Article  CAS  PubMed  Google Scholar 

  • Liu ZG, Qi ZC, Liu WL, Wang WZ (2015) Lutein protects against ischemia/reperfusion injury in rat kidneys. Mol Med Rep 11:2179–2184

    CAS  PubMed  Google Scholar 

  • Lui WY, Lee WM (2006) Regulation of junction dynamics in the testis—transcriptional and post-translational regulations of cell junction proteins. Mol Cell Endocrinol 16:25–35

    Article  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25:402–408

    Article  CAS  PubMed  Google Scholar 

  • Lysiak JJ, Nguyen QAT, Kirby JL, Turner TT (2003) Ischemia-reperfusion of the murine testis stimulates the expression of proinflammatory cytokines and activation of c-jun N-terminal kinase in a pathway to E-selectin expression. Biol Reprod 69:202–210

    Article  CAS  PubMed  Google Scholar 

  • Mangels AR, Holden JM, Beecher GR, Forman MR, Lanza E (1993) Carotenoid content of fruits and vegetables: an evaluation of analytic data. J Am Diet Assoc 93:284–296

    Article  CAS  PubMed  Google Scholar 

  • Mann DL (2003) Stress-activated cytokines and the heart: from adaptation to maladaptation. Annu Rev Physiol 65:81–101

    Article  CAS  PubMed  Google Scholar 

  • Martianov I, Fimia GM, Dierich A, Parvinen M, Sassone-Corsi P, Davidson I (2001) Late arrest of spermiogenesis and germ cell apoptosis in mice lacking the TBP-like TLF/TRF2 gene. Mol Cell 7:509–515

    Article  CAS  PubMed  Google Scholar 

  • Mazaud-Guittot S, Meugnier E, Pesenti S, Wu X, Vidal H, Gow A, Le Magueresse-Battistoni B (2010) Claudin 11 deficiency in mice results in loss of the Sertoli cell epithelial phenotype in the testis. Biol Reprod 82:202–213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mehraein F, Negahdar F (2011) Morphometric evaluation of seminiferous tubules in aged mice testes after melatonin administration. Cell J 13:1–4

    CAS  PubMed  PubMed Central  Google Scholar 

  • Meinhardt A, Bacher M, Metz C, Bucala R, Wreford N, Lan H, Atkins R, Hedger M (1998) Local regulation of macrophage subsets in the adult rat testis: examination of the roles of the seminiferous tubules, testosterone, and macrophage-migration inhibitory factor. Biol Reprod 59:371–378

    Article  CAS  PubMed  Google Scholar 

  • Morita K, Sasaki H, Fujimoto K, Furuse M, Tsukita S (1991) Claudin-11/OSP-based tight junctions of myelin sheaths in brain and Sertoli cells in testis. J Cell Biol 145:579–588

    Article  Google Scholar 

  • Mueller S, Rosenquist TA, Takai Y, Bronson RA, Wimmer E (2003) Loss of nectin-2 at Sertoli-spermatid junctions leads to male infertility and correlates with severe spermatozoan head and midpiece malformation, impaired binding to the zona pellucida, and oocyte penetration. Biol Reprod 69:1330–1340

    Article  CAS  PubMed  Google Scholar 

  • Murphy K, Carvajal L, Medico L, Pepling M (2005) Expression of Stat3 in germ cells of developing and adult mouse ovaries and testes. Gene Expr Patterns 5:475–482

    Article  CAS  PubMed  Google Scholar 

  • Nah WH, Lee JE, Park HJ, Park NC, Gye MC (2011) Claudin-11 expression increased in spermatogenic defect in human testes. Fertil Steril 95:385–388

    Article  CAS  PubMed  Google Scholar 

  • Nakata H, Wakayama T, Takai Y, Iseki S (2015) Quantitative analysis of the cellular composition in seminiferous tubules in normal and genetically modified infertile mice. J Histochem Cytochem 63:99–113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nantel F, Monaco L, Foulkes NS, Masquilier D, LeMeur M, Henriksen K, Dietrich A, Parvinen M, Sassone-Corsi P (1996) Spermtogenesis deficiency and germ cell apoptosis in CREM-mutant mice. Nature 380:159–162

    Article  CAS  PubMed  Google Scholar 

  • Newton SC, Blaschuk OW, Millette CF (1993) N-cadherin mediates Sertoli cell-spermatogenic cell adhesion. Dev Dynam 197:1–13

    Article  CAS  Google Scholar 

  • Ogura W, Itagaki S, Kurokawa T, Noda T, Hirano T, Mizuno S, Iseki K (2006) Protective effect of lutein on ischemia-reperfusion injury in rat small intestine. Biol Pharm Bull 29:1764–1766

    Article  CAS  PubMed  Google Scholar 

  • Ojima F, Sakamoto H, Ishiguro Y, Terao J (1993) Consumption of carotenoids in photosensitized oxidation of human plasma and plasma low-density lipoprotein. Free Radic Biol Med 15:377–384

    Article  CAS  PubMed  Google Scholar 

  • Ozaki-Kuroda K, Nakanishi H, Ohta H, Tanaka H, Kurihara H, Mueller S, Irie K, Ikeda W, Sakai T, Wimmer E, Nishimune Y, Takai Y (2002) Nectin couples cell-cell adhesion and the actin scaffold at heterotypic testicular junctions. Curr Biol 12:1145–1150

    Article  CAS  PubMed  Google Scholar 

  • Paul C, Robaire B (2013) Impaired function of the blood-testis barrier during aging is preceded by a decline in cell adhesion proteins and GTPases. PLoS ONE 8:e84354–e84363

    Article  PubMed  PubMed Central  Google Scholar 

  • Pentikainen V, Erkkila K, Suomalainen L, Otala M, Pentikainen MO, Parvinen M, Dunkel L (2001) TNFa down-regulates the Fas ligand and inhibits germ cell apoptosis in the human testis. J Clin Endocrinol Metab 86:4480–4488

    CAS  PubMed  Google Scholar 

  • Ribaya-Mercado JD, Blumberg JB (2004) Lutein and zeaxanthin and their potential roles in disease prevention. J Am Coll Nutr 23:567S–587S

    Article  CAS  PubMed  Google Scholar 

  • Saitou M, Furuse M, Sasaki H, Schulzke JD, Fromm M, Takano H, Noda T, Tsukita S (2000) Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol Biol Cell 11:4131–4142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sassone-Corsi P (2000) CREM: a master-switch regulating the balance between differentiation and apoptosis in male germ cells. Mol Reprod Dev 56:228–229

    Article  CAS  PubMed  Google Scholar 

  • Siu MKY, Lee WM, Cheng CY (2003) The interplay of collagen IV, tumor necrosis factor-a, gelatinase B (matrix metalloprotease-9), and tissue inhibitor of metalloproteases-1 in the basal lamina regulates Sertoli cell-tight junction dynamics in the rat testis. Endocrinology 144:371–387

    Article  CAS  PubMed  Google Scholar 

  • Sommerburg O, Keunen JE, Bird AC, van Kuijk FJ (1998) Fruits and vegetables that are sources for lutein and zeaxanthin: the macular pigment in human eyes. Br J Ophthalmol 82:907–910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Subczynski WK, Wisniewska A, Widomska J (2010) Location of macular xanthophylls in the most vulnerable regions of photoreceptor outer-segment membranes. Arch Biochem Biophys 27:61–66

    Article  Google Scholar 

  • Suescun MO, Rival C, Theas MS, Calandra RS, Lustig L (2003) Involvement of tumor necrosis factor-alpha in the pathogenesis of autoimmune orchitis in rats. Biol Reprod 68:2114–2121

    Article  CAS  PubMed  Google Scholar 

  • Suleman N, Somers S, Smith R, Opie LH, Lecour SC (2008) Dual activation of STAT-3 and Akt is required during the trigger phase of ischaemic preconditioning. Cardiovasc Res 79:127–133

    Article  CAS  PubMed  Google Scholar 

  • Takai Y, Nakanishi H (2003) Nectin and afadin: novel organizers of intercellular junctions. J Cell Sci 116:17–27

    Article  CAS  PubMed  Google Scholar 

  • Takehashi M, Kanatsu-Shinohara M, Miki H, Lee J, Kazuki Y, Inoue K, Ogonuki N, Toyokuni S, Oshimura M, Ogura A, Shinohara T (2007) Production of knockout mice by gene targeting in multipotent germline stem cells. Dev Biol 312:344–352

    Article  CAS  PubMed  Google Scholar 

  • ves-Rodrigues A, Shao A (2004) The science behind lutein. Toxicol Lett 150:57–83

    Article  Google Scholar 

  • Warren DW, Pasupuleti V, Lu Y, Platter BW, Horton R (1990) Tumor necrosis factor and interleukin-1 stimulate testosterone secretion in adult male rat Leydig cells in vitro. J Androl 11:353–360

    CAS  PubMed  Google Scholar 

  • Wei SM, Yan ZZ, Zhou J (2008) Role of cAMP-responsive element modulator tau (CREMtau) in ipsilateral testicular injury after unilateral testicular torsion-detorsion. Fertil Steril 89:1737–1742

    Article  CAS  PubMed  Google Scholar 

  • Wong CH, Cheng CY (2005) The blood–testis barrier: its biology, regulation, and physiological role in spermatogenesis. Curr Top Dev Biol 71:263–296

    Article  CAS  PubMed  Google Scholar 

  • Wong EW, Cheng CY (2011) Impacts of environmental toxicants on male reproductive dysfunction. Trends Pharmacol Sci 32:290–299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Woo TT, Li SY, Lai WW, Wong D, Lo AC (2013) Neuroprotective effects of lutein in a rat model of retinal detachment. Graefes Arch Clin Exp Ophthalmol 251:41–51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • York JP, Drago JR (1985) Torsion and contralateral testicle. J Urol 133:294–297

    CAS  PubMed  Google Scholar 

  • Yule TD, Tung KSK (1993) Experimental autoimmune orchitis induced by testis and sperm antigen-specific T cell clones: an important pathogenic cytokine is tumor necrosis factor. Endocrinology 133:1098–1107

    CAS  PubMed  Google Scholar 

  • Zhang D, Penttila TL, Morris PL, Teichmann M, Roeder RG (2001) Spermiogenesis deficiency in mice lacking the TRF2 gene. Science 292:1153–1155

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Wong CH, Xia W, Mruk DD, Lee NPY, Lee WM, Cheng CY (2005) Regulation of Sertoli–germ cell adherens junction dynamics via changes in protein-protein interactions of the N-cadherin-b-catenin protein complex which are possibly mediated by c-Src and MTMR2: an in vivo study using an androgen suppression model. Endocrinology 146:1268–1284

    Article  CAS  PubMed  Google Scholar 

  • Zhang S, Zeng Y, Qu J, Luo Y, Wang X, Li W (2013a) Endogenous EGF maintains Sertoli germ cell anchoring junction integrity and is required for early recovery from acute testicular ischemia/reperfusion injury. Reproduction 145:177–189

    Article  CAS  PubMed  Google Scholar 

  • Zhang WX, Qin JC, Wang R, Wang L, Zhang J (2013b) Radiation-induced oxidative stress and claudin-11 mRNA expression in the testis. Zhonghua Nan Ke Xue 19:306–310

    CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by Kuwait University Research Grant SRU02/13. The authors thank Shabeeba Pattillath and Preethi George for their excellent technical support. The authors HFA, MSB, and INQ have contributed equally to the study.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Medicine-Kuwait University, P.O. Box: 24923, Safat, 13110, Jabriyah, Kuwait

    May Al-Maghrebi, Hoda F. Al-Somali, Marina S. Botras & Iman N. Qadhi

  2. Department of Anatomy, Faculty of Medicine-Kuwait University, Jabriyah, Kuwait

    Waleed M. Renno

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  1. May Al-Maghrebi
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  3. Hoda F. Al-Somali
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Correspondence to May Al-Maghrebi.

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Animal maintenance was conducted in strict accordance with the recommendations of Kuwait University’s guidelines for experimental animals for their well-being and care. The ethical use of animals at Kuwait University is in accordance with the norms of the International Council for Laboratory Animal Sciences (ICLAS).

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Al-Maghrebi, M., Renno, W.M., Al-Somali, H.F. et al. Lutein modulates transcription dysregulation of adhesion molecules and spermatogenesis transcription factors induced by testicular ischemia reperfusion injury: it could be SAFE. Naunyn-Schmiedeberg's Arch Pharmacol 389, 539–551 (2016). https://doi.org/10.1007/s00210-016-1223-9

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