NDLI: Depletion of selenoprotein GPx4 in spermatocytes causes male infertility in mice.

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Depletion of selenoprotein GPx4 in spermatocytes causes male infertility in mice.

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Depletion of selenoprotein GPx4 in spermatocytes causes male infertility in mice.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Suzuki, Toshiyuki Suzuki, Jyunko Tajima, Yoko Naito, Shinsaku Konishi, Kumiko Minami, Shintaro Hakkaku, Nao Iwamoto, Ryo Shioda, Seiji Ishizaka, Kazuhiro Imai, Hirotaka Ichinose, Shizuko Arata, Satoru Nishimura, Masuhiro Nakagawa, Yasuhito
Description	Author Affiliation: Imai H ( School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. imaih@pharm.kitasato-u.ac.jp)
Abstract	Phospholipid hydroperoxide glutathione peroxidase (GPx4) is an intracellular antioxidant enzyme that directly reduces peroxidized phospholipids. GPx4 is strongly expressed in the mitochondria of testis and spermatozoa. We previously found a significant decrease in the expression of GPx4 in spermatozoa from 30% of infertile human males diagnosed with oligoasthenozoospermia (Imai, H., Suzuki, K., Ishizaka, K., Ichinose, S., Oshima, H., Okayasu, I., Emoto, K., Umeda, M., and Nakagawa, Y. (2001) Biol. Reprod. 64, 674-683). To clarify whether defective GPx4 in spermatocytes causes male infertility, we established spermatocyte-specific GPx4 knock-out mice using a Cre-loxP system. All the spermatocyte-specific GPx4 knock-out male mice were found to be infertile despite normal plug formation after mating and displayed a significant decrease in the number of spermatozoa. Isolated epididymal GPx4-null spermatozoa could not fertilize oocytes in vitro. These spermatozoa showed significant reductions of forward motility and the mitochondrial membrane potential. These impairments were accompanied by the structural abnormality, such as a hairpin-like flagella bend at the midpiece and swelling of mitochondria in the spermatozoa. These results demonstrate that the depletion of GPx4 in spermatocytes causes severe abnormalities in spermatozoa. This may be one of the causes of male infertility in mice and humans.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	47
Volume Number	284
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2009-11-20
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Glutathione Peroxidase Metabolism Infertility, Male Enzymology Spermatocytes Animals Epididymis Fertilization In Vitro Membrane Potentials Mice Mice, Inbred C57BL Mice, Knockout Mitochondria Reactive Oxygen Species Time Factors Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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