Decreased LONP1 expression contributes to DNA damage and meiotic defects in oocytes

Author:

Liu Chuanming12,Xu Manlin12,Guan Yajie12,Li Lilin12,Liu Wenwen12,Guo Bichun12,Sheng Xiaoqiang12,Zhang Yang12,Zhou Jidong12,Zhen Xin12,Yan Guijun12,Sun Haixiang12,Ding Lijun1234ORCID

Affiliation:

1. Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital Nanjing University Medical School Nanjing China

2. Center for Molecular Reproductive Medicine Nanjing University Nanjing China

3. State Key Laboratory of Analytic Chemistry for Life Science Nanjing University Nanjing China

4. Clinical Center for Stem Cell Research The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing China

Abstract

AbstractMeiotic defects in oocytes are the primary reason for decreased female fertility with advanced maternal age. In this study, we revealed that decreased expression of ATP‐dependent Lon peptidase 1 (LONP1) in aged oocytes and oocyte‐specific depletion of LONP1 disrupt oocyte meiotic progression accompanying with mitochondrial dysfunction. In addition, LONP1 downregulation increased oocyte DNA damage. Moreover, we demonstrated that splicing factor proline and glutamine rich directly interacts with LONP1 and mediate the effect of LONP1 depletion on meiotic progression in oocytes. In summary, our data suggest that decreased expression of LONP1 is involved in advanced maternal age‐related meiosis defects and that LONP1 represents a new therapeutic target to improve aged oocyte quality.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Jiangsu Province

Publisher

Wiley

Subject

Cell Biology,Developmental Biology,Genetics

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