TY - JOUR
T1 - Ubiquitin-activating enzyme E1 inhibitor PYR-41 retards sperm enlargement after fusion to the egg
AU - Yoshida, Keiichi
AU - Kang, Woojin
AU - Nakamura, Akihiro
AU - Kawano, Natsuko
AU - Hanai, Maito
AU - Miyado, Mami
AU - Miyamoto, Yoshitaka
AU - Iwai, Maki
AU - Hamatani, Toshio
AU - Saito, Hidekazu
AU - Miyado, Kenji
AU - Umezawa, Akihiro
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.reprotox.2018.01.001
DO - 10.1016/j.reprotox.2018.01.001
M3 - Article
C2 - 29355596
AN - SCOPUS:85042935197
SN - 0890-6238
VL - 76
SP - 71
EP - 77
JO - Reproductive Toxicology
JF - Reproductive Toxicology
ER -