title: Lutein modulates transcription dysregulation of adhesion molecules and spermatogenesis transcription factors induced by testicular ischemia reperfusion injury: it could be SAFE.
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.
authors.affiliation: Department of Biochemistry, Faculty of Medicine-Kuwait University, P.O. Box: 24923, Safat, 13110, Jabriyah, Kuwait. malmaghrebi@hsc.edu.kw.
authors.forename: May
authors.identifier: http://orcid.org/0000-0001-8927-0485
authors.initials: M
authors.lastname: Al-Maghrebi
authors.affiliation: Department of Anatomy, Faculty of Medicine-Kuwait University, Jabriyah, Kuwait.
authors.forename: Waleed M
authors.initials: WM
authors.lastname: Renno
authors.affiliation: Department of Biochemistry, Faculty of Medicine-Kuwait University, P.O. Box: 24923, Safat, 13110, Jabriyah, Kuwait.
authors.forename: Hoda F
authors.initials: HF
authors.lastname: Al-Somali
authors.affiliation: Department of Biochemistry, Faculty of Medicine-Kuwait University, P.O. Box: 24923, Safat, 13110, Jabriyah, Kuwait.
authors.forename: Marina S
authors.initials: MS
authors.lastname: Botras
authors.affiliation: Department of Biochemistry, Faculty of Medicine-Kuwait University, P.O. Box: 24923, Safat, 13110, Jabriyah, Kuwait.
authors.forename: Iman N
authors.initials: IN
authors.lastname: Qadhi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D053613:Janus Kinase 1 / Q000378:metabolism; D014975:Lutein / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; C506237:Tnfrsf1a protein, rat; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D053613:Janus Kinase 1; D053148:Caspase 3; D053181:Caspase 8; D014975:Lutein
keywords: Adhesion molecules; Apoptosis; Lutein; Spermatogenesis; Testicular ischemia reperfusion injury; Transcription factors