Melatonin Protects against LPS-Induced Mitochondrial Dyshomeostasis and Ovarian Damage through JNK Signaling Pathway in Mouse Ovary

Ling-Ge Shi ^1,2,3, Si-Min Ding ^1,2, Tong-Kun Guo ⁴

¹Department of Obstetrics and Gynecology, NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
²Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, Hefei, 230032, Anhui, China.
³Anhui Provincial Institute of Translational Medicine, Hefei, 230032, Anhui, China.
⁴Zhejiang lab, 1818 Wenyi Street, Hangzhou, 311500, Zhejiang, China.
⁵Institute of Brain Science, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China.
⁶Department of Medical Service, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China.
⁷Assisted Reproductive Technology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
⁸Joint Laboratory in Reproductive Medicine, Chinese University of Hong Kong-Sichuan University, The Chinese University of Hong Kong, Hong Kong, China.
⁹Zhejiang lab, 1818 Wenyi Street, Hangzhou, 311500, Zhejiang, China. rain2011@zhejianglab.com.
¹⁰Department of Obstetrics and Gynecology, NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. caoyunxia6@126.com.
¹¹Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, Hefei, 230032, Anhui, China. caoyunxia6@126.com.
¹²Anhui Provincial Institute of Translational Medicine, Hefei, 230032, Anhui, China. caoyunxia6@126.com.
¹³Department of Obstetrics and Gynecology, NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. yjl@ustc.edu.cn.
¹⁴Engineering Research Center of Biopreservation and Artificial Organs, Ministry of Education, Hefei, 230032, Anhui, China. yjl@ustc.edu.cn.
¹⁵Anhui Provincial Institute of Translational Medicine, Hefei, 230032, Anhui, China. yjl@ustc.edu.cn.

⁰Department of Obstetrics and Gynecology, NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.

Reproductive Sciences (thousand Oaks, Calif.) +

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August 13, 2025

View abstract on PubMed

Summary

Melatonin (MT) protects against diminished ovarian reserve (DOR) by activating the JNK pathway. This treatment improves mitochondrial function, reduces inflammation and autophagy, and enhances ovarian reserve.

Area Of Science

Reproductive biology
Mitochondrial medicine
Inflammation research

Background

Diminished ovarian reserve (DOR) is linked to mitochondrial dysfunction and inflammation.
Melatonin (MT) shows protective effects against ovarian injury, but its mechanism in LPS-induced DOR is unclear.

Purpose Of The Study

To investigate the effects and mechanisms of melatonin (MT) on lipopolysaccharide (LPS)-induced ovarian reserve dysfunction.
To explore MT's role in counteracting mitochondrial dysfunction and inflammation in DOR.

Main Methods

HE staining and follicle counting in mouse models.
Immunofluorescence, Western blotting, and qPCR to analyze molecular mechanisms.
Assessing reactive oxygen species (ROS) and mitochondrial function in KGN cells.

Main Results

LPS reduced anti-Mullerian hormone (AMH) and GDF9; MT treatment reversed this.
MT alleviated LPS-induced follicular depletion and modulated mitochondrial dynamics proteins (OPA1, DRP1).
LPS increased autophagy and ROS; MT suppressed these and activated the JNK pathway.

Conclusions

Melatonin (MT) restores mitochondrial fusion/fission balance and enhances ovarian reserve.
MT activates the JNK signaling pathway, suppressing inflammation and autophagy.
MT effectively improves overall ovarian function in the context of LPS-induced DOR.

Keywords:

Diminished ovarian reserve Excessive autophagy JNK signaling pathway LPS Melatonin Mitochondrial dyshomeostasis