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Induction of apoptosis mediated by Fas receptor and activation of caspase-3 in MRL-+/+ or MRL-lpr/lpr murine oocytes

  • Maowu Guo (a1), Eimei Sato (a2), Xiang Li (a2), Etsuko Mori (a1), Shigeru Saito (a3) and Tsuneatsu Mori (a3)...

Abstract

The molecular mechanisms leading to ovarian follicular atresia in the typical pathways of programmed cell death remain to be clarified. Here we have demonstrated that the apoptotic signalling pathway in MRL-+/+ (MRL/+) murine oocytes is through the Fas receptor followed by the activation of caspase-3. In contrast, we found that the aberrant expression and dysfunction of the mutant Fas receptor in MRL-lpr/lpr (MRL/lpr) murine oocytes caused by insertion of the early transposable element (ETn) into the Fas gene were associated with an inability to activate the caspase cascade (especially caspase-3) and to induce nuclear DNA fragmentation. These findings indicate that the induction of apoptosis in MRL/lpr murine oocytes did not occur in the presence of a defective Fas receptor lacking the death domain to trigger the caspase cascade, suggesting a failure to induce ovarian follicular atresia.

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Corresponding author

All correspondence to: Tsuneatsu Mori, MD, PhD, Department of Immunology, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minatoku, Tokyo, 108-0071, Japan. Fax: +81 3 5449 5261. e-mail: ts-mori@ims.u-tokyo.ac.jp

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