title: Sertoli cell is a potential target for perfluorooctane sulfonate-induced reproductive dysfunction in male mice.
abstract: Perfluorooctane sulfonate (PFOS) is associated with male reproductive disorders, but its targets and mechanisms are poorly understood. We used in vitro and in vivo models to explore the roles of Sertoli cells and the blood-testis barrier (BTB) in PFOS-induced male reproductive dysfunction. First, we used primary Sertoli cell to estimate PFOS-induced cytotoxicity, junction proteins expression, and the changes of barrier function. ICR mice were then administered PFOS (0.25-50mg/kg/day) for 4 weeks. Sperm count, ultrastructure and permeability of the Sertoli cell-based BTB, and testicular PFOS were estimated. Furthermore, the expression and localization of proteins related to junctions between Sertoli cells and mitogen-activated protein kinase (MAPK) signaling pathway were evaluated. Apparent decreases in sperm count were found. PFOS significantly increased vacuolization in Sertoli cells in seminiferous tubules and BTB ultrastructural disassembly, which subsequently increased BTB permeability and testicular PFOS levels, which was confirmed by in vitro results that PFOS decreased transepithelial electrical resistance between Sertoli cells. Additionally, PFOS decreased the expression of junction proteins in Sertoli cells, which was further confirmed by in vivo results that PFOS decreased or dislocated junction proteins (i.e., ZO-1, occludin, claudin-11, and connexin-43) and increased proteins related to the MAPK signaling pathway (i.e., Erk and p38), whereas basal ectoplasmic specialization proteins did not change. The results were confirmed by SB203580, a p38 MAPK selective inhibitor. Sertoli cells appear to be a new cellular target for PFOS. Together with disruption of BTB integrity and function, these cells play an important role in PFOS-induced male reproductive toxicity.
authors.affiliation: State Key Lab of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, People's Republic of China.
authors.forename: Lianglin
authors.initials: L
authors.lastname: Qiu
authors.forename: Xuhui
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhang
authors.forename: Yudong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.forename: Minjian
authors.initials: M
authors.lastname: Chen
authors.forename: Zhan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
authors.forename: Shou-Lin
authors.initials: SL
authors.lastname: Wang
mesh_terms: D017738:Alkanesulfonic Acids / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005466:Fluorocarbons / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012708:Sertoli Cells / Q000187:drug effects* / Q000473:pathology; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects; D062725:Tight Junction Proteins / Q000032:analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
chemical_list: D017738:Alkanesulfonic Acids; D005466:Fluorocarbons; D062725:Tight Junction Proteins; C076994:perfluorooctane sulfonic acid; D048051:p38 Mitogen-Activated Protein Kinases
keywords: MAPK signal pathway.; Sertoli cells; blood-testis barrier; male reproductive dysfunction; perfluorooctane sulfonate