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While its use in Europe, Canada and the U.S. has been banned due to its human toxicity, it continues to be used in China and other developing countries as a global pollutant. Herein, using an<jats:italic>in vitro<\/jats:italic>model of Sertoli cell blood-testis barrier (BTB), PFOS was found to induce Sertoli cell injury by perturbing actin cytoskeleton through changes in the spatial expression of actin regulatory proteins. Specifically, PFOS caused mis-localization of Arp3 (actin-related protein 3, a branched actin polymerization protein) and palladin (an actin bundling protein). These disruptive changes thus led to a dis-organization of F-actin across Sertoli cell cytosol, causing truncation of actin microfilament, thereby failing to support the Sertoli cell morphology and adhesion protein complexes (e.g., occludin-ZO-1, CAR-ZO-1, and N-cadherin-\u00df-catenin), through a down-regulation of p-Akt1-S473 and p-Akt2-S474. The use of SC79, an Akt1\/2 activator, was found to block the PFOS-induced Sertoli cell injury by rescuing the PFOS-induced F-actin dis-organization. These findings thus illustrate PFOS exerts its disruptive effects on Sertoli cell function downstream through Akt1\/2. As such, PFOS-induced male reproductive dysfunction can possibly be managed through an intervention on Akt1\/2 expression.<\/jats:p>","DOI":"10.1038\/s41598-017-01016-8","type":"journal-article","created":{"date-parts":[[2017,4,18]],"date-time":"2017-04-18T15:58:12Z","timestamp":1492531092000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Perfluorooctanesulfonate (PFOS)-induced Sertoli cell injury through a disruption of F-actin and microtubule organization is mediated by Akt1\/2"],"prefix":"10.1038","volume":"7","author":[{"given":"Ying","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiqi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wing-yee","family":"Lui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Will M.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolores D.","family":"Mruk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3117-3791","authenticated-orcid":false,"given":"C. 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