PMID- 36821035 OWN - NLM STAT- MEDLINE DCOM- 20230721 LR - 20230722 IS - 1933-7205 (Electronic) IS - 1933-7191 (Linking) VI - 30 IP - 8 DP - 2023 Aug TI - Oxidative Stress and Cell Cycle Arrest in Seminiferous Tubules Nearby Varicose Vessels: New Perspectives from Experimental Varicocele. PG - 2401-2415 LID - 10.1007/s43032-023-01200-4 [doi] AB - Varicocele (VCL) has been shown to induce severe oxidative stress in the testicular tissue resulting in 35% of males with primary infertility. To compare the exacerbating impacts of varicose on oxidative DNA damage and homeostatic antioxidant reactions in the seminiferous tubules (ST), enclosed and far from varicose vessels. Thirty mature Wistar rats were divided into control and VCL-induced groups. To approve VCL, the testicular diameters, volume, and blood circulation were measured using B-mode and Doppler ultrasonography. Next, to confirm oxidative stress (OS), the global homeostatic antioxidant biomarkers were evaluated. Moreover, the OS-induced oxidative DNA damage and homeostatic antioxidant reactions were compared between STs nearby and far from varicose vessels. Finally, to clarify the DNA damage-induced impact on the cell cycle progression, the global and local expressions of Cyclin D1, Cdk4, and p21 were examined. The VCL-induced group exhibited diminished global antioxidant status (marked with TAC, GPX, SOD, and CAT) and UNG and MPG expression levels. Moreover, the cross-sections of the VCL group represented a prominent reduction in the UNG, MPG, Cyclin D1, and cdk4, and upregulation in the p21 expression levels, more prominently in the STs nearby varicose vessels. Concerning severe oxidative DNA damage and intensive molecular changes in the STs nearby the varicose vessels, they can be considered the main cause of oxidative DNA damage in enclosed tubules. Thus, the varicose-mediated oxidative DNA damage negatively impacts the cell cycle progression in the tubules more intensively in the subcapsular area. CI - (c) 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation. FAU - Minas, Aram AU - Minas A AUID- ORCID: 0000-0001-9763-1041 AD - Department of Surgery, Division of Urology, Human Reproduction Section, Universidade Federal de Sao Paulo- UNIFESP, Sao Paulo, Brazil. FAU - Razi, Mazdak AU - Razi M AUID- ORCID: 0000-0002-4309-4831 AD - Department of Basic Science, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran. Mazdak.razi@gmail.com. FAU - Nasr-Esfahani, Mohammad Hossein AU - Nasr-Esfahani MH AUID- ORCID: 0000-0003-1983-3435 AD - Department of Animal Biotechnology, Jahad Daneshgahi Biotechnology Research Institute, Royan Research Institute, Reproductive Medical Research Center, Isfahan, Iran. FAU - Hashemi-Asl, Seyed Mohammad AU - Hashemi-Asl SM AUID- ORCID: 0000-0003-3909-2144 AD - Department of Surgery and Diagnostic Imaging, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran. FAU - Tavalaee, Marziyeh AU - Tavalaee M AUID- ORCID: 0000-0001-9954-964X AD - Department of Animal Biotechnology, Jahad Daneshgahi Biotechnology Research Institute, Royan Research Institute, Reproductive Medical Research Center, Isfahan, Iran. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230223 PL - United States TA - Reprod Sci JT - Reproductive sciences (Thousand Oaks, Calif.) JID - 101291249 RN - 0 (Antioxidants) RN - 136601-57-5 (Cyclin D1) SB - IM MH - Rats MH - Male MH - Humans MH - Animals MH - *Antioxidants/pharmacology MH - *Varicocele/metabolism MH - Cyclin D1/metabolism MH - Rats, Wistar MH - Testis/metabolism MH - Oxidative Stress MH - Seminiferous Tubules/metabolism MH - Cell Cycle Checkpoints OTO - NOTNLM OT - Cell cycle OT - DNA repairmen OT - Oxidative stress OT - Varicocele OT - Varicose vessels EDAT- 2023/02/24 06:00 MHDA- 2023/07/21 06:43 CRDT- 2023/02/23 11:36 PHST- 2022/11/08 00:00 [received] PHST- 2023/02/08 00:00 [accepted] PHST- 2023/07/21 06:43 [medline] PHST- 2023/02/24 06:00 [pubmed] PHST- 2023/02/23 11:36 [entrez] AID - 10.1007/s43032-023-01200-4 [pii] AID - 10.1007/s43032-023-01200-4 [doi] PST - ppublish SO - Reprod Sci. 2023 Aug;30(8):2401-2415. doi: 10.1007/s43032-023-01200-4. Epub 2023 Feb 23.