P-613 Deletion of the CLPP gene in oocytes exacerbates chemotherapy-induced ovarian damage

Abstract

Abstract Study question We attempted to investigate the role of the Clpp in chemotherapy-induced ovarian damage and the decline of oocyte function Summary answer We clarified that the deletion of Clpp gene in oocytes will aggravate the ovarian damage and the decline of oocyte function caused by chemotherapeutic drugs. What is known already Chemotherapy is extensively used to treat cancers and is often associated with ovarian damage which leads to premature ovarian insufficiency and infertility. Mitochondria have the critical role of producing energy and maintaining normal cellular activities for oocyte maturation and folliculogenesis. Study design, size, duration This study used a mouse model with oocyte-specific deletion of mitochondrial stress response gene Caseinolytic peptidase P (Clpp) to investigate mitochondrial homeostasis in oocytes from mice receiving a chemotherapeutic drug cyclophosphamide (CTX). Participants/materials, setting, methods First, analyze the reproductive phenotype and fertility test of mice, observe the ovarian development, the proportion of follicles at all levels, the spindle of oocytes and the aneuploidy rate of chromosomes at the MII stage, and using multiple mitochondrial function indicator kit to detect mitochondrial function. Then, we modeled 8-week-old mice with a single injection of 100ul 75uM cyclophosphamide. After 14 days, check the above indicators again. the impact of cyclophosphamide modeling will be analyzed. Main results and the role of chance We found the specific deletion of Clpp in oocytes reduced fecundity of the mice at advanced age. The Clpp deletion led to meiotic defects and impaired mitochondrial distribution and function in the MII oocytes. CTX induction further affected oocyte competence in Clpp cKO mice and lead to an exhaustive disruption of blastocytes formation due to the severe effects on mitochondrial distributions and functions. Limitations, reasons for caution We only clarified that the deletion of Clpp gene in oocytes will through affecting the mitochondrial function aggravate the ovarian damage and the decline of oocyte function caused by chemotherapeutic drugs.But the underlying mechanism has not been able to explore further. Wider implications of the findings This is first study specifically on the impact of oocyte specific deletion of Clpp on oocyte competence and early embryo development. At the same time, the role of Clpp gene in the ovary damaged by chemotherapy drugs was further clarified. Trial registration number not applicable