Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta

Takahisa Nakamura; Ryoji Yao; Takehiko Ogawa; Toru Suzuki; Chizuru Ito; Naoki Tsunekawa; Kimiko Inoue; Rieko Ajima; Takashi Miyasaka; Yutaka Yoshida; Atsuo Ogura; Kiyotaka Toshimori; Toshiaki Noce; Tadashi Yamamoto; Tetsuo Noda

doi:10.1038/ng1344

Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta

Takahisa Nakamura, Ryoji Yao, Takehiko Ogawa, Toru Suzuki, Chizuru Ito, Naoki Tsunekawa, Kimiko Inoue, Rieko Ajima, Takashi Miyasaka, Yutaka Yoshida, Atsuo Ogura, Kiyotaka Toshimori, Toshiaki Noce, Tadashi Yamamoto, Tetsuo Noda

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100 Citations (Scopus)

Abstract

Spermatogenesis is a complex process that involves cooperation of germ cells and testicular somatic cells. Various genetic disorders lead to impaired spermatogenesis, defective sperm function and male infertility. Here we show that Cnot7^-/- males are sterile owing to oligo-astheno-teratozoospermia, suggesting that Cnot7, a CCR4-associated transcriptional cofactor, is essential for spermatogenesis. Maturation of spermatids is unsynchronized and impaired in seminiferous tubules of Cnot7 ^-/- mice. Transplantation of spermatogonial stem cells from male Cnot7^-/- mice to seminiferous tubules of Kit mutant mice (Kit ^W/W-v) restores spermatogenesis, suggesting that the function of testicular somatic cells is damaged in the Cnot7^-/- condition. The testicular phenotypes of Cnot7^-/- mice are similar to those of mice deficient in retinoid X receptor beta (Rxrb). We further show that Cnot7 binds the AF-1 domain of Rxrb and that Rxrb malfunctions in the absence of Cnot7. Therefore, Cnot7 seems to function as a coregulator of Rxrb in testicular somatic cells and is thus involved in spermatogenesis.

Original language	English
Pages (from-to)	528-533
Number of pages	6
Journal	Nature Genetics
Volume	36
Issue number	5
DOIs	https://doi.org/10.1038/ng1344
Publication status	Published - 2004 May
Externally published	Yes

ASJC Scopus subject areas

Genetics

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@article{c6e860fd663847b2af0d36fb6503e6f9,

title = "Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta",

abstract = "Spermatogenesis is a complex process that involves cooperation of germ cells and testicular somatic cells. Various genetic disorders lead to impaired spermatogenesis, defective sperm function and male infertility. Here we show that Cnot7-/- males are sterile owing to oligo-astheno-teratozoospermia, suggesting that Cnot7, a CCR4-associated transcriptional cofactor, is essential for spermatogenesis. Maturation of spermatids is unsynchronized and impaired in seminiferous tubules of Cnot7 -/- mice. Transplantation of spermatogonial stem cells from male Cnot7-/- mice to seminiferous tubules of Kit mutant mice (Kit W/W-v) restores spermatogenesis, suggesting that the function of testicular somatic cells is damaged in the Cnot7-/- condition. The testicular phenotypes of Cnot7-/- mice are similar to those of mice deficient in retinoid X receptor beta (Rxrb). We further show that Cnot7 binds the AF-1 domain of Rxrb and that Rxrb malfunctions in the absence of Cnot7. Therefore, Cnot7 seems to function as a coregulator of Rxrb in testicular somatic cells and is thus involved in spermatogenesis.",

author = "Takahisa Nakamura and Ryoji Yao and Takehiko Ogawa and Toru Suzuki and Chizuru Ito and Naoki Tsunekawa and Kimiko Inoue and Rieko Ajima and Takashi Miyasaka and Yutaka Yoshida and Atsuo Ogura and Kiyotaka Toshimori and Toshiaki Noce and Tadashi Yamamoto and Tetsuo Noda",

note = "Funding Information: We thank J. Yanagisawa, Y. Sugitani, T. Nakazawa, M. Ohsugi, T. Tezuka, K. Semba and M. Noda for discussions; S. Kato for providing expression vectors for nuclear receptors and reporter plasmids containing response elements for nuclear receptors; N. Yanai for providing TTE3 cells; and H. Yamanaka, N. Kusaka, A. Nakamura, M. Yoneda, A. Moriya and F. Suzuki-Toyota for technical support. This work was supported by a Grant for Advanced Cancer Research from the Ministry of Education, Science, Sports, and Culture of Japan and grants from the Organization for Pharmaceutical Safety and Research of Japan, and from the Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists.",

year = "2004",

month = may,

doi = "10.1038/ng1344",

language = "English",

volume = "36",

pages = "528--533",

journal = "Nature Genetics",

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T1 - Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta

AU - Nakamura, Takahisa

AU - Yao, Ryoji

AU - Ogawa, Takehiko

AU - Suzuki, Toru

AU - Ito, Chizuru

AU - Tsunekawa, Naoki

AU - Inoue, Kimiko

AU - Ajima, Rieko

AU - Miyasaka, Takashi

AU - Yoshida, Yutaka

AU - Ogura, Atsuo

AU - Toshimori, Kiyotaka

AU - Noce, Toshiaki

AU - Yamamoto, Tadashi

AU - Noda, Tetsuo

N1 - Funding Information: We thank J. Yanagisawa, Y. Sugitani, T. Nakazawa, M. Ohsugi, T. Tezuka, K. Semba and M. Noda for discussions; S. Kato for providing expression vectors for nuclear receptors and reporter plasmids containing response elements for nuclear receptors; N. Yanai for providing TTE3 cells; and H. Yamanaka, N. Kusaka, A. Nakamura, M. Yoneda, A. Moriya and F. Suzuki-Toyota for technical support. This work was supported by a Grant for Advanced Cancer Research from the Ministry of Education, Science, Sports, and Culture of Japan and grants from the Organization for Pharmaceutical Safety and Research of Japan, and from the Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists.

PY - 2004/5

Y1 - 2004/5

N2 - Spermatogenesis is a complex process that involves cooperation of germ cells and testicular somatic cells. Various genetic disorders lead to impaired spermatogenesis, defective sperm function and male infertility. Here we show that Cnot7-/- males are sterile owing to oligo-astheno-teratozoospermia, suggesting that Cnot7, a CCR4-associated transcriptional cofactor, is essential for spermatogenesis. Maturation of spermatids is unsynchronized and impaired in seminiferous tubules of Cnot7 -/- mice. Transplantation of spermatogonial stem cells from male Cnot7-/- mice to seminiferous tubules of Kit mutant mice (Kit W/W-v) restores spermatogenesis, suggesting that the function of testicular somatic cells is damaged in the Cnot7-/- condition. The testicular phenotypes of Cnot7-/- mice are similar to those of mice deficient in retinoid X receptor beta (Rxrb). We further show that Cnot7 binds the AF-1 domain of Rxrb and that Rxrb malfunctions in the absence of Cnot7. Therefore, Cnot7 seems to function as a coregulator of Rxrb in testicular somatic cells and is thus involved in spermatogenesis.

AB - Spermatogenesis is a complex process that involves cooperation of germ cells and testicular somatic cells. Various genetic disorders lead to impaired spermatogenesis, defective sperm function and male infertility. Here we show that Cnot7-/- males are sterile owing to oligo-astheno-teratozoospermia, suggesting that Cnot7, a CCR4-associated transcriptional cofactor, is essential for spermatogenesis. Maturation of spermatids is unsynchronized and impaired in seminiferous tubules of Cnot7 -/- mice. Transplantation of spermatogonial stem cells from male Cnot7-/- mice to seminiferous tubules of Kit mutant mice (Kit W/W-v) restores spermatogenesis, suggesting that the function of testicular somatic cells is damaged in the Cnot7-/- condition. The testicular phenotypes of Cnot7-/- mice are similar to those of mice deficient in retinoid X receptor beta (Rxrb). We further show that Cnot7 binds the AF-1 domain of Rxrb and that Rxrb malfunctions in the absence of Cnot7. Therefore, Cnot7 seems to function as a coregulator of Rxrb in testicular somatic cells and is thus involved in spermatogenesis.

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DO - 10.1038/ng1344

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Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta

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