Melatonin enhances the developmental potential of immature oocytes from older reproductive-aged women by improving mitochondrial function
Dandan Yang,
Yaoqin Mu,
Jing Wang,
Weiwei Zou,
Huijuan Zou,
Han Yang,
Chao Zhang,
Yongqi Fan,
Heng Zhang,
Huan Zhang,
Beili Chen,
Zhiguo Zhang
Affiliations
Dandan Yang
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.81Meishan Road, Hefei, 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No.81Meishan Road, Hefei, 230032, Anhui, China
Yaoqin Mu
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
Jing Wang
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.81Meishan Road, Hefei, 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No.81Meishan Road, Hefei, 230032, Anhui, China
Weiwei Zou
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.81Meishan Road, Hefei, 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No.81Meishan Road, Hefei, 230032, Anhui, China
Huijuan Zou
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.81Meishan Road, Hefei, 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No.81Meishan Road, Hefei, 230032, Anhui, China
Han Yang
Obstetrics and Gynaecology Hospital of Fudan University, 413 Zhaozhou Road, Huangpu District, 200000, Shanghai, China
Chao Zhang
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.81Meishan Road, Hefei, 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No.81Meishan Road, Hefei, 230032, Anhui, China
Yongqi Fan
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.81Meishan Road, Hefei, 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No.81Meishan Road, Hefei, 230032, Anhui, China
Heng Zhang
Hefei No 1 High School, 2356 Xizang Road, Hefei, 230032, Anhui, China
Huan Zhang
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.81Meishan Road, Hefei, 230032, Anhui, China
Beili Chen
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.81Meishan Road, Hefei, 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No.81Meishan Road, Hefei, 230032, Anhui, China; Corresponding author. Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.81Meishan Road, Hefei, 230032, Anhui, China.
Zhiguo Zhang
Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.81Meishan Road, Hefei, 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No.81Meishan Road, Hefei, 230032, Anhui, China; Corresponding author. Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No.81Meishan Road, Hefei, 230032, Anhui, China.
Aims: To evaluate whether melatonin (MT) supplementation during in vitro maturation (IVM) of human oocytes can reverse the age-related decline in oocyte quality. Main methods: We enrolled 172 patients aged ≥35 years (older reproductive-aged women) and 83 patients aged <35 years (young women) who underwent in vitro fertilization between 2019 and 2022. We conducted IVM with and without 10 μM MT in immature oocytes of different ages. Oocyte fertilization and embryo development were observed using a stereomicroscope. We assessed the immunofluorescence intensity of mitochondrial function, measured the copy number of mitochondrial DNA (mtDNA), and examined the spindle and chromosome composition in in vitro mature stage II (IVM-MII) oocytes using immunofluorescence and second-generation sequencing. Key findings: MT supplementation significantly improved the redox level in the IVM medium and IVM-MII oocytes in older reproductive-aged women. It also significantly increased the proportion of circular mtDNA and the adenosine triphosphate content in IVM-MII oocytes. In addition, the IVM-MII oocytes obtained with MT supplementation showed a significant improvement in the normal composition of the spindle and chromosomes. Thus, the aged immature oocytes also showed significantly improved maturation and blastocyst formation rates owing to the role of MT. Significance: Supplementation with 10 μM MT in the IVM medium reverses the age-related decline in oocyte quality. Our findings provide a viable solution for enhancing fertility in older reproductive-aged women.
