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By generating a conditional knockout (cKO) of Dicer1 in the proximal part of the mouse epididymis, we studied the role of RNA interference in epididymal functions. The Dicer1 cKO epididymis displayed an altered lipid homeostasis associated with a 0.6\u2010fold reduction in the expression of the gene elongation of very long chain fatty acids\u2010like 2, an enzyme needed for production of long\u2010chain polyunsaturated fatty acids (PUFAs). Furthermore, the expression of several factors involved in cholesterol synthesis was up\u2010regulated. Accordingly, the Dicer1 cKO sperm membrane showed a 0.7\u2010fold decrease in long\u2010chain PUFAs, whereas the amount of cholesterol in acrosome\u2010reacted sperm displayed a 1.7\u2010fold increase. The increased cholesterol:PUFA ratio of the sperm membrane caused breakage of the neck and acrosome region and immotility of sperm. Dicer1 cKO mice sperm also displayed reduced ability to bind to and fertilize the oocyte in vitro. This study thus shows that Dicer1 is critical for lipid synthesis in the epididymis, which directly affects sperm membrane integrity and male fertility.\u2014Bj\u00f6rkgren, I., Gylling, H., Turunen, H., Huhtaniemi, I., Strauss, L., Poutanen, M., Sipil\u00e4, P. Imbalanced lipid homeostasis in the conditional Dicer1 knockout mouse epididymis causes instability of the sperm membrane.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 29, 433\u2010442 (2015).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.14-259382","type":"journal-article","created":{"date-parts":[[2014,11,4]],"date-time":"2014-11-04T01:13:54Z","timestamp":1415063634000},"page":"433-442","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Imbalanced lipid homeostasis in the conditional Dicer1 knockout mouse epididymis causes instability of the sperm membrane"],"prefix":"10.1096","volume":"29","author":[{"given":"Ida","family":"Bj\u00f6rkgren","sequence":"first","affiliation":[{"name":"Department of Physiology Institute of 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