title: Association of semen cytokines with reactive oxygen species and histone transition abnormalities.
abstract: OBJECTIVE
  The aim of this study is to investigate the relationships among reactive oxygen species (ROS) elevation, histone transition, and seminal cytokine concentrations.
  
  
  METHODS
  Total levels of ROS in semen samples from 6560 men were measured. From this sample, 118 cases with high ROS and 106 controls were recruited. Basic semen parameters and histone-to-protamine ratios were analyzed, 400 semen cytokine and receptor alterations were assayed by protein chip, and finally 18 cytokines were validated in each sample using a Bio-Plex Cytokine assay.
  
  
  RESULTS
  The results showed that the seminal ROS concentration was associated with abnormalities in the sperm histone transition. Compared with controls, 93 cytokines had significant alterations in the high ROS cases, with 14 of them further verified in individual samples. The concentrations of CXCL5, CXCL16, CXCL8, IL-1b, IL-10, CSF3, CCL3, and TNF-α were significantly correlated with the histone transition ratio. In addition, IL-16 showed significantly different concentrations in controls, normal semen with high ROS levels, and abnormal semen with high ROS levels.
  
  
  CONCLUSIONS
  Semen ROS are associated with abnormalities in sperm histone transition. CXCL5, CXCL8, IL-16, CCL8, CCL22, CCL20, CXCL16, IL-1B, IL-6, IL-7, IL-10, CSF3, CCL3, CCL4, and TNF-α all have elevated concentrations in semen with high ROS levels. These data might help to explain the mechanisms behind the increase in the levels of ROS and seminal cytokines and their relationship with defective spermatogenesis.
authors.affiliation: Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Mo
authors.affiliation: Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
authors.forename: Xingcheng
authors.initials: X
authors.lastname: Gao
authors.affiliation: Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China. guangy23@sina.com.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China. guangy23@sina.com.|, Rm 806, Teaching Building, No.63 Duobao Rd, Guangzhou, 510150, China. guangy23@sina.com.
authors.forename: Bolan
authors.initials: B
authors.lastname: Yu
mesh_terms: D000328:Adult; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007248:Infertility, Male / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011479:Protamines / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013081:Sperm Motility / Q000235:genetics; D013091:Spermatogenesis / Q000235:genetics; D013094:Spermatozoa / Q000378:metabolism / Q000473:pathology
chemical_list: D016207:Cytokines; D006657:Histones; D011479:Protamines; D017382:Reactive Oxygen Species
keywords: Histone-to-protamine transition; ROS; Semen quality; Seminal cytokine