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Updated: Nov 3, 2025
Defining the Program of Maternal mRNA Translation during In vitro Maturation using a Single Oocyte Reporter Assay
Published on: June 16, 2021
Transcriptomic study of the mechanism by which the Kai Yu Zhong Yu recipe improves oocyte quality in a stressed mouse
Xiaoli Zhao1, Ruihong Ma1, Xiaoyu Zhang1
1Reproductive Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, And National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China.
Ethnopharmacological Relevance:
The Kai Yu Zhong Yu recipe (KYZY) is a classic herbal formula in traditional Chinese medicine (TCM) that has been used to treat infertility associated with psychological stress for more than three hundred years.
Aim Of The Study:
Psychological stress has major impacts on fertility, with variable outcomes depending on the nature, strength, and duration of the stress. Stress can directly disturb ovulation, oocyte quality, maturation, and embryo development. The aim of this study is to investigate the molecular mechanism by which KYZY improves oocyte developmental potential under psychological stress.
Materials And Methods:
ICR female mice aged 4-5 weeks were randomly divided into five groups: control, stressed in the chronic unpredictable stress model (CUSM), and stressed plus KYZY treatment at 38.2 g/kg (KYZYH), 19.1 g/kg (KYZYM), or 9.6 g/kg (KYZYL). Ovary function was assessed by measuring serum levels of estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and anti-Müllerian hormone (AMH). Oocyte quality was evaluated in terms of reactive oxygen species (ROS) levels, apoptotic DNA fragmentation, and mitochondria distribution. We used RNA sequencing (RNAseq) to identify differentially expressed genes (DEGs) between groups and then further analyzed the DEGs for gene ontology (GO) term enrichment and protein-protein interactions.
Results:
Mice in the stressed group had reduced serum E2, LH, and FSH as well as increased ROS levels, increased apoptosis, and disturbed mitochondria distribution in oocytes. Treatment with KYZY at all three doses reversed or ameliorated these negative effects of stress. DEG analysis identified 187 common genes between the two comparisons (stressed vs. control and KYZYM vs. stressed), 33 of which were annotated with six gene ontology (GO)'s biological process (BP) terms: cell differentiation, apoptosis, ATP synthesis, protein homo-oligomerization, neuron migration, and negative regulation of peptidase activity. Protein-protein interaction network analysis of DEGs identified key hub genes. Notably, the genes Atp5o and Cyc1 were both involved in the ATP synthesis and among the top three hub genes, suggesting that regulation of oocyte mitochondrial electron transport and ATP synthesis is important in the response to stress and also is a possible mechanism of action for KYZY.
Conclusions:
KYZY was effective in ameliorating the adverse effects of stress on oocyte competence, possibly by targeting the mitochondrial respiratory chain and ATP synthase.
