Related Experiment Video
Updated: Sep 10, 2025
Xenopus laevis as a Model to Identify Translation Impairment
Published on: September 27, 2015
Mevalonate metabolites boost aged oocyte quality through prenylation of small GTPases
Chuanming Liu1,2,3, Huidan Zhang1,2,3, Jialian Mao4
1Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Abstract:
Declining oocyte quality is the major contributor to female subfertility in aged mammals. Currently, there are no effective interventions to ameliorate aged oocyte quality. Here we found that oocytes at metaphase I from the cumulus-oocyte complexes of aged mice showed reduced cortical F-actin and lower levels of mevalonate (MVA) pathway metabolites, including MVA, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate. We further showed that MVA supplementation improved FPP levels, cortical F-actin and the quality of aged oocytes. Mechanistically, we found that MVA supplementation induced granulosa cells to synthesize FPP, which was subsequently transferred to aged oocytes. Transported FPP increased the prenylation of small GTPases, including CDC42 and RAC1, and promoted membrane localization of CDC42-N-WASP-Arp2/3 and RAC1-WAVE2-Arp2/3 complexes, promoting cortical F-actin reassembly and reducing aneuploidy of aged oocytes. We also identified a natural chemical compound, 8-isopentenyl flavone, with an isopentenyl side chain from Epimedium brevicornu Maxim, which could increase CDC42 and RAC1 prenylation, improving the cortical F-actin and the competence of aged oocytes, and ameliorating reproductive outcomes in aged female mice. Collectively, increasing the prenylation of small GTPases via MVA metabolites or 8-isopentenyl flavone provides a therapeutic approach for boosting female fertility during reproductive aging.
Insights
Supplementing mevalonate (MVA) or using 8-isopentenyl flavone can restore aged oocyte quality by enhancing actin structure and GTPase prenylation, offering a potential fertility treatment.
Area of Science:
- Reproductive Biology
- Cellular and Molecular Biology
- Gerontology
Background:
- Female reproductive aging is characterized by declining oocyte quality, leading to subfertility.
- Current interventions to improve aged oocyte quality are lacking.
- Aged mouse oocytes exhibit reduced cortical F-actin and lower mevalonate (MVA) pathway metabolites.
Purpose of the Study:
- To investigate the role of MVA pathway metabolites in aged oocyte quality.
- To identify interventions that can ameliorate age-related decline in oocyte quality.
- To explore the therapeutic potential of natural compounds for reproductive aging.
Main Methods:
- Analysis of cortical F-actin and MVA pathway metabolites in aged mouse oocytes.
- Supplementation with MVA and assessment of oocyte quality and F-actin levels.
- Investigation of FPP transfer from granulosa cells to oocytes.
- Evaluation of the effects of 8-isopentenyl flavone on oocyte quality and reproductive outcomes.
Main Results:
- MVA supplementation improved FPP levels, cortical F-actin, and overall aged oocyte quality.
- MVA supplementation induced granulosa cells to synthesize FPP, which was transferred to oocytes, enhancing GTPase prenylation (CDC42, RAC1) and cortical F-actin.
- 8-isopentenyl flavone increased GTPase prenylation and cortical F-actin, improving oocyte competence and reproductive outcomes in aged mice.
- These interventions reduced aneuploidy in aged oocytes.
Conclusions:
- Enhancing mevalonate pathway metabolites or using 8-isopentenyl flavone can restore aged oocyte quality.
- Increasing small GTPase prenylation via MVA metabolites or 8-isopentenyl flavone is a promising therapeutic strategy for reproductive aging.
- This approach offers a novel therapeutic avenue for boosting female fertility during reproductive aging.
Related Concept Videos
02:07Oogenesis
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...
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,...
01:37Mitochondria
01:39Mitochondrial Precursor Proteins
Most of the mitochondrial...