Peripubertal requirement of Tsg101 in maintaining the integrity of membranous structures in mouse oocytes

Abstract

Objective: As a component of Endosomal Sorting Complex Required for Transport (ESCRT) complex I, the tumor susceptibility gene 101 (Tsg101) carries out multiple functions. In this work, we report that oocyte-specific deletion of tumor susceptibility gene 101 (Tsg101) leads to age-dependent oocyte demise in mice. Materials and Method: Tsg101 floxed mice (Tsg101 f/f ) were bred with Zp3 cre transgenic mice to examine oocyte-specific roles of Tsg101. Multiple cellular and molecular biological approaches were taken to examine what leads to oocyte demise in the absence of Tsg101. Results: The death of oocytes from Zp3 cre /Tsg101 f/f (Tsg101 d/d thereafter) mice showed a strong correlation with sexual maturation, as gonadotropin-releasing hormone antagonist injections improved the survival rate of oocytes from 5-week-old Tsg101 d/d mice. Maturation of oocytes from prepubertal Tsg101 d/d mice proceeded normally, but was largely abnormal in oocytes from peripubertal Tsg101 d/d mice, showing shrinkage or rupture. Endolysosomal structures in oocytes from peripubertal Tsg101 d/d mice showed abnormalities, with aberrant patterns of early and late endosomal markers and a high accumulation of lysosomes. Dying oocytes showed plasma membrane blebs and leakage. Blockage of endocytosis in oocytes at 4 C Hyejin Shin and Dayoung Park contributed equally to this study.

Exosomes: Diagnostic and Therapeutic Implications in Cancer

“…ESCRT consists of four complexes: ESCRT-0, -I, -II, and -III. The components of ESCRT include apoptosis-linked gene 2-interacting protein X (ALIX), tumor susceptibility gene 101 (TSG101), and vacuolar protein sorting-associated protein 4 (VPS4) [ 34 , 35 , 36 ]. Clathrin, which is recruited by ESCRT-0, is necessary for sorting membrane cargo, recruiting lipid modifiers, and efficient ILV formation [ 37 ].…”