title: Rescue of perfluorooctanesulfonate (PFOS)-mediated Sertoli cell injury by overexpression of gap junction protein connexin 43.
abstract: Perfluorooctanesulfonate (PFOS) is an environmental toxicant used in developing countries, including China, as a stain repellent for clothing, carpets and draperies, but it has been banned in the U.S. and Canada since the late 2000s. PFOS perturbed the Sertoli cell tight junction (TJ)-permeability barrier, causing disruption of actin microfilaments in cell cytosol, perturbing the localization of cell junction proteins (e.g., occluden-ZO-1, N-cadherin-ß-catenin). These changes destabilized Sertoli cell blood-testis barrier (BTB) integrity. These findings suggest that human exposure to PFOS might induce BTB dysfunction and infertility. Interestingly, PFOS-induced Sertoli cell injury associated with a down-regulation of the gap junction (GJ) protein connexin43 (Cx43). We next investigated if overexpression of Cx43 in Sertoli cells could rescue the PFOS-induced cell injury. Indeed, overexpression of Cx43 in Sertoli cells with an established TJ-barrier blocked the disruption in PFOS-induced GJ-intercellular communication, resulting in the re-organization of actin microfilaments, which rendered them similar to those in control cells. Furthermore, cell adhesion proteins that utilized F-actin for attachment became properly distributed at the cell-cell interface, resealing the disrupted TJ-barrier. In summary, Cx43 is a good target that might be used to manage PFOS-induced reproductive dysfunction.
authors.affiliation: The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, 1230 York Ave, New York 10065, New York, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, 1230 York Ave, New York 10065, New York, USA.
authors.forename: Dolores D
authors.initials: DD
authors.lastname: Mruk
authors.affiliation: The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, 1230 York Ave, New York 10065, New York, USA.
authors.forename: Haiqi
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Biology, Hong Kong Baptist University, Hong Kong, China.
authors.forename: Chris K C
authors.initials: CK
authors.lastname: Wong
authors.affiliation: School of Biological Sciences, The University of Hong Kong, Hong Kong, China.
authors.forename: Will M
authors.initials: WM
authors.lastname: Lee
authors.affiliation: The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, 1230 York Ave, New York 10065, New York, USA.
authors.forename: C Yan
authors.initials: CY
authors.lastname: Cheng
mesh_terms: D017738:Alkanesulfonic Acids / Q000009:adverse effects*; D000818:Animals; D001814:Blood-Testis Barrier / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D018031:Connexin 43 / Q000235:genetics* / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004785:Environmental Pollutants / Q000009:adverse effects*; D005466:Fluorocarbons / Q000009:adverse effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects
chemical_list: D017738:Alkanesulfonic Acids; D018031:Connexin 43; D004785:Environmental Pollutants; D005466:Fluorocarbons; C580592:Gja1 protein, rat; C076994:perfluorooctane sulfonic acid