Related Experiment Video
Updated: Nov 24, 2025
Meiotic Spindle Assessment in Mouse Oocytes by siRNA-mediated Silencing
Published on: October 11, 2015
Mitochondria-targeted therapeutics, MitoQ and BGP-15, reverse aging-associated meiotic spindle defects in mouse and
Usama Al-Zubaidi1,2, Deepak Adhikari1, Ozgur Cinar1,3
1Development and Stem Cell Program and Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia.
Study Question:
Do mitochondria-targeted therapies reverse ageing- and oxidative stress-induced spindle defects in oocytes from mice and humans?
Summary Answer:
Exposure to MitoQ or BGP-15 during IVM protected against spindle and chromosomal defects in mouse oocytes exposed to oxidative stress or derived from reproductively aged mice whilst MitoQ promoted nuclear maturation and protected against chromosomal misalignments in human oocytes.
What Is Known Already:
Spindle and chromosomal abnormalities in oocytes are more prevalent with maternal aging, increasing the risk of aneuploidy, miscarriage and genetic disorders such as Down's syndrome. The origin of compromised oocyte function may be founded in mitochondrial dysfunction and increased reactive oxygen species (ROS).
Study Design, Size, Duration:
Oocytes from young and old mice were treated with MitoQ and/or BGP-15 during IVM. To directly induce mitochondrial dysfunction, oocytes were treated with H2O2, and then treated the MitoQ and/or BGP-15. Immature human oocytes were cultured with or without MitoQ. Each experiment was repeated at least three times, and data were analyzed by unpaired-sample t-test or chi-square test.
Participants/Materials, Setting, Methods:
Immature germinal vesicle (GV) stage oocytes from 1-, 12- and 18-month-old mice were obtained from preovulatory ovarian follicles. Oocytes were treated with MitoQ and/or BGP-15 during IVM. GV-stage human oocytes were cultured with or without MitoQ. Mitochondrial membrane potential and mitochondrial ROS were measured by live-cell imaging. Meiotic spindle and chromosome alignments were visualized by immunofluorescent labeling of fixed oocytes and the 3-dimensional images were analyzed by Imaris.
Main Results And The Role Of Chance:
MitoQ or BGP-15 during IVM protects against spindle and chromosomal defects in oocytes exposed to oxidative stress and in oocytes from aged mice (P < 0.001). In human oocytes, the presence of MitoQ during IVM promoted nuclear maturation and had a similar positive effect in protecting against chromosomal misalignments (P < 0.001).
Limitations, Reasons For Caution:
Our study identifies two excellent candidates that may help to improve fertility in older women. However, these potential therapies must be tested for efficacy in clinical IVM systems, and undergo thorough examination of resultant offspring in preclinical models before utilization.
Wider Implications Of The Findings:
Our results using in-vitro systems for oocyte maturation in both mouse and human provide proof of principle that mitochondrially targeted molecules such as MitoQ and BGP-15 may represent a novel therapeutic approach against maternal aging-related spindle and chromosomal abnormalities.
Study Funding/Competing Interest(S):
The project was financially supported by the National Health and Medical Research Council and Australian Research Council, Australia. U.A.-Z. was supported by the Iraqi Higher Education and Scientific Research Ministry PhD scholarship and O.C. was supported by TUBITAK-1059B191601275. M.P.M. consults for MitoQ Inc. and holds patents in mitochondria-targeted therapies. R.L.R. is an inventor on patents relating to the use of BGP-15 to improve gamete quality.
Trial Registration Number:
N/A.
Insights
Mitochondria-targeted therapies like MitoQ and BGP-15 show promise in preventing spindle and chromosomal defects in oocytes. These treatments may improve fertility outcomes for older women by addressing age-related oocyte dysfunction.
Area of Science:
- Reproductive biology
- Mitochondrial medicine
- Oocyte quality and aging
Background:
- Maternal aging increases oocyte abnormalities, risking aneuploidy and genetic disorders.
- Mitochondrial dysfunction and increased reactive oxygen species (ROS) are implicated in compromised oocyte function.
Purpose of the Study:
- To investigate if mitochondria-targeted therapies can reverse age- and oxidative stress-induced spindle defects in mouse and human oocytes.
- To evaluate the efficacy of MitoQ and BGP-15 in improving oocyte quality during in-vitro maturation (IVM).
Main Methods:
- Oocytes from young and aged mice, and immature human oocytes, were treated with MitoQ and/or BGP-15 during IVM.
- Oxidative stress was induced using H2O2 in mouse oocytes.
- Mitochondrial function, spindle/chromosome alignment, and nuclear maturation were assessed.
Main Results:
- MitoQ and BGP-15 protected mouse oocytes from oxidative stress and aging-related defects.
- MitoQ promoted nuclear maturation and protected human oocytes against chromosomal misalignments.
- Significant improvements were observed in both mouse and human oocytes (P < 0.001).
Conclusions:
- Mitochondria-targeted molecules like MitoQ and BGP-15 offer a potential novel therapeutic strategy for maternal aging-related oocyte abnormalities.
- These findings provide proof of principle for using such therapies to enhance fertility in older women.
Related Concept Videos
02:57Meiosis vs. Mitosis
Before the start of mitosis and meiosis I, the cell synthesizes DNA, resulting in two homologous copies of each chromosome. DNA synthesis is...
01:37Mitochondria
03:09Meiosis I
Prophase I is the most extended and complex step of meiosis I characterized by synapsis, chromosome pairing, and recombination of the homologous chromosomes. This process is facilitated by a proteinaceous structure called the...
02:02Meiosis II
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...