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Updated: Jul 24, 2025
Author Spotlight: Understanding DNA Damage Response in Mammalian Oocytes and Preimplantation Embryos
Published on: June 23, 2023
Decreased LONP1 expression contributes to DNA damage and meiotic defects in oocytes
Chuanming Liu1,2, Manlin Xu1,2, Yajie Guan1,2
1Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
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.
Insights
Decreased ATP-dependent Lon peptidase 1 (LONP1) in aged oocytes impairs meiosis and increases DNA damage, contributing to reduced female fertility. Restoring LONP1 may improve oocyte quality in advanced maternal age.
Area of Science:
- Reproductive biology
- Molecular genetics
- Cellular aging
Background:
- Meiotic errors in oocytes are a major cause of infertility in women with advanced maternal age.
- The molecular mechanisms underlying age-related oocyte dysfunction are not fully understood.
Purpose of the Study:
- To investigate the role of ATP-dependent Lon peptidase 1 (LONP1) in aged oocytes.
- To explore the impact of LONP1 downregulation on oocyte meiotic progression and mitochondrial function.
- To identify potential therapeutic targets for improving aged oocyte quality.
Main Methods:
- Studied LONP1 expression in aged oocytes.
- Utilized oocyte-specific LONP1 depletion models.
- Assessed meiotic progression, mitochondrial function, and DNA damage.
- Investigated interactions between LONP1 and splicing factors.
Main Results:
- Reduced LONP1 expression was observed in aged oocytes.
- Oocyte-specific LONP1 depletion disrupted meiosis and caused mitochondrial dysfunction.
- LONP1 downregulation led to increased DNA damage in oocytes.
- Splicing factor proline and glutamine rich was found to interact with LONP1, mediating its effects on meiosis.
Conclusions:
- Decreased LONP1 expression is implicated in the meiotic defects associated with advanced maternal age.
- LONP1 plays a crucial role in maintaining oocyte meiotic progression and quality.
- LONP1 represents a potential therapeutic target for enhancing aged oocyte quality and improving female fertility.
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