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Bushen Tiaojing decoction ameliorates meiotic impairment to improve oocyte quality during aging through blocking the
1Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei Collaborative Innovation Center of Integrated Traditional and Western Medicine on Reproductive Disease, Institute of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China.
Abstract:
The decline in oocyte quality is a key factor contributing to the age-related deterioration of female fertility. In women of advanced maternal age, impaired oocyte development is primarily manifested as meiotic abnormalities. An important underlying pathological mechanism is mitochondrial dysfunction, which is often associated with iron overload during aging. Previous studies have suggested that the traditional Chinese medicine formula Bushen Tiaojing Decoction (BSTJD) may improve oocyte quality; however, its specific protective effects in women of advanced maternal age and the related mechanisms remain unclear. This study aimed to investigate whether BSTJD ameliorates meiotic defects in oocytes from aged mice by inhibiting aging-related iron overload. We established both naturally aged and FeSO4-induced iron overload mouse models, followed by BSTJD intervention. In vitro experiments, oocytes from aged mice were cultured and treated with BSTJD-containing serum or adenovirus infection. The results indicated that BSTJD may improve oocyte quality under advanced maternal age conditions by inhibiting iron overload and enhancing mitochondrial function. BSTJD suppressed iron overload-induced reactive oxygen species accumulation, thereby downregulating p53 and p21 expression, promoting CDK1 expression, and reducing ESPL1 expression. Through this regulatory mechanism, BSTJD prevented premature cleavage of chromosomal cohesin by ESPL1, thereby supporting the normal completion of meiosis in aged oocytes and reducing the occurrence of spindle abnormalities and aneuploidy. This study suggests that BSTJD may improve oocyte quality in aged mice by inhibiting iron overload and its downstream p53/CDK1/ESPL1 signaling pathway. This work provides experimental evidence for the clinical application of BSTJD and offers a potential target for intervention strategies aimed at improving oocyte quality decline in women of advanced maternal age.
Insights
Bushen Tiaojing Decoction (BSTJD) improves oocyte quality in aged mice by reducing iron overload and enhancing mitochondrial function. This traditional Chinese medicine protects against meiotic abnormalities, offering potential fertility treatments for advanced maternal age.
Area of Science:
- Reproductive biology
- Gerontology
- Pharmacology
Background:
- Oocyte quality decline is a major cause of age-related infertility.
- Mitochondrial dysfunction and iron overload are key pathological mechanisms in aged oocytes.
- Traditional Chinese medicine, Bushen Tiaojing Decoction (BSTJD), shows potential for improving oocyte quality.
Purpose of the Study:
- To investigate if BSTJD ameliorates meiotic defects in aged mouse oocytes by inhibiting iron overload.
- To elucidate the underlying molecular mechanisms of BSTJD's protective effects.
Main Methods:
- Established naturally aged and iron overload mouse models.
- Administered BSTJD intervention and performed in vitro oocyte culture with BSTJD-treated serum.
- Utilized adenovirus infection for gene manipulation and analyzed meiotic progression, spindle morphology, and aneuploidy.
Main Results:
- BSTJD improved oocyte quality in aged mice by inhibiting iron overload and enhancing mitochondrial function.
- BSTJD suppressed reactive oxygen species (ROS) accumulation, downregulated p53/p21, promoted CDK1, and reduced ESPL1 expression.
- BSTJD prevented premature cleavage of chromosomal cohesin, reducing spindle abnormalities and aneuploidy in aged oocytes.
Conclusions:
- BSTJD improves oocyte quality in aged mice by inhibiting iron overload and modulating the p53/CDK1/ESPL1 signaling pathway.
- BSTJD offers a potential therapeutic strategy for improving oocyte quality and addressing age-related infertility in women.
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