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

Chuanming Liu; Manlin Xu; Yajie Guan; Lilin Li; Wenwen Liu; Bichun Guo; Xiaoqiang Sheng; Yang Zhang; Jidong Zhou; Xin Zhen; Guijun Yan; Haixiang Sun; Lijun Ding

doi:10.1002/mrd.23694

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

Mol Reprod Dev. 2023 Jun;90(6):358-368. doi: 10.1002/mrd.23694. Epub 2023 Jul 1.

Authors

Chuanming Liu^{1

2}, Manlin Xu^{1

2}, Yajie Guan^{1

2}, Lilin Li^{1

2}, Wenwen Liu^{1

2}, Bichun Guo^{1

2}, Xiaoqiang Sheng^{1

2}, Yang Zhang^{1

2}, Jidong Zhou^{1

2}, Xin Zhen^{1

2}, Guijun Yan^{1

2}, Haixiang Sun^{1

2}, Lijun Ding^{1

2

3

4}

Affiliations

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.

PMID: 37392095
DOI: 10.1002/mrd.23694

Abstract

Meiotic 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.

Keywords: LONP1; SFPQ; meiotic defect; mitochondrial dysfunction; oocyte aging.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
DNA Damage
Female
Meiosis
Mice
Oocytes* / metabolism
Peptide Hydrolases* / metabolism

Substances

Peptide Hydrolases
LONP1 protein, mouse