*Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland; Turku Doctoral Programme of Biomedical Sciences, Turku, Finland; Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Department of Medicine, Division of Internal Medicine, University of Helsinki, Helsinki, Finland; Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, London, United Kingdom; Turku Center for Disease Modeling, University of Turku, Turku, Finland; Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; **Department of Physiology, Institute of Biomedicine, University of Helsinki, Helsinki, Finland; and Laboratory Animal Centre, University of Helsinki, Helsinki, Finland.
*Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland; Turku Doctoral Programme of Biomedical Sciences, Turku, Finland; Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Department of Medicine, Division of Internal Medicine, University of Helsinki, Helsinki, Finland; Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, London, United Kingdom; Turku Center for Disease Modeling, University of Turku, Turku, Finland; Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; **Department of Physiology, Institute of Biomedicine, University of Helsinki, Helsinki, Finland; and Laboratory Animal Centre, University of Helsinki, Helsinki, Finland
FASEB J. 2015 Feb;29(2):433-42. doi: 10.1096/fj.14-259382. Epub 2014 Nov 3.
During epididymal sperm maturation, the lipid content of the sperm membrane is modified, which facilitates sperm motility and fertility. However, little is known about the mechanisms regulating the maturation process. 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-fold reduction in the expression of the gene elongation of very long chain fatty acids-like 2, an enzyme needed for production of long-chain polyunsaturated fatty acids (PUFAs). Furthermore, the expression of several factors involved in cholesterol synthesis was up-regulated. Accordingly, the Dicer1 cKO sperm membrane showed a 0.7-fold decrease in long-chain PUFAs, whereas the amount of cholesterol in acrosome-reacted sperm displayed a 1.7-fold 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.
在附睾精子成熟过程中，精子膜的脂质含量发生改变，这有助于精子的运动和生育能力。然而，对于调节成熟过程的机制知之甚少。通过在小鼠附睾的近端生成 Dicer1 的条件性敲除（cKO），我们研究了 RNA 干扰在附睾功能中的作用。Dicer1 cKO 附睾显示出脂质稳态的改变，与长链多不饱和脂肪酸（PUFA）生产所需的酶——延伸非常长链脂肪酸样 2 基因的表达降低了 0.6 倍。此外，参与胆固醇合成的几个因子的表达上调。因此，Dicer1 cKO 精子膜中的长链 PUFAs 减少了 0.7 倍，而顶体反应精子中的胆固醇含量增加了 1.7 倍。精子膜中胆固醇：PUFA 比值的增加导致颈部和顶体区域的断裂以及精子的不动性。Dicer1 cKO 小鼠精子的体外结合和受精能力也降低。因此，本研究表明 Dicer1 对附睾中的脂质合成至关重要，这直接影响精子膜的完整性和男性生育能力。
