Ubiquitin-activating enzyme E1 inhibitor PYR-41 retards sperm enlargement after fusion to the egg

Keiichi Yoshida, Woojin Kang, Akihiro Nakamura, Natsuko Kawano, Maito Hanai, Mami Miyado, Yoshitaka Miyamoto, Maki Iwai, Toshio Hamatani, Hidekazu Saito, Kenji Miyado, Akihiro Umezawa

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1 Citation (Scopus)

Abstract

The ubiquitin-proteasome system, which is initiated by a single ubiquitin-activating enzyme E1 (UBE1), is involved in male reproduction via spermatogenesis and function in mammals. Here we explored the influence of UBE1-specific inhibitor, 4[4-(5-nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester (pyrazone-41 or PYR-41) in female reproduction. UBE-1 was detected by immunoblotting and immunocytochemistry in mouse eggs and was localized mainly under the egg plasma membrane. PYR-41 pretreatment suppresses the development of eggs into two-cell embryos. Specifically, pretreatment retarded sperm enlargement and meiotic chromosomal division after sperm-egg fusion. PYR-41 pretreatment disturbed β-catenin, a well-known target protein for ubiquitination, localization under the egg plasma membrane and on spindle microtubules in wild-type eggs. Otherwise, PYR-41 treatment had no effect on the two-cell development of eggs lacking β-catenin. Our results raise the possibility that inhibition of the ubiquitin-proteasome system suppresses sperm enlargement through impaired β-catenin-mediated mechanism.

Original languageEnglish
Pages (from-to)71-77
Number of pages7
JournalReproductive Toxicology
Volume76
DOIs
Publication statusPublished - 2018 Mar 1

Keywords

  • PYR-41
  • Sperm enlargement
  • UBE1
  • Ubiquitin-proteasome system
  • β-catenin

ASJC Scopus subject areas

  • Toxicology

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    Yoshida, K., Kang, W., Nakamura, A., Kawano, N., Hanai, M., Miyado, M., Miyamoto, Y., Iwai, M., Hamatani, T., Saito, H., Miyado, K., & Umezawa, A. (2018). Ubiquitin-activating enzyme E1 inhibitor PYR-41 retards sperm enlargement after fusion to the egg. Reproductive Toxicology, 76, 71-77. https://doi.org/10.1016/j.reprotox.2018.01.001