Backgroud: abnormalities or defects in oocyte meiosis can result in decreased oocyte quality, reduced ovarian reserve, and female diseases. However, the mechanisms of oocyte meiosis remain largely unknown, especially epigenetic regulation. Here, we explored the role of EZH1/2 (histone methyltransferase of H3K27) in mouse oocyte meiosis by inhibiting its activity and deleting its gene.
Results: with embryonic ovary cultured in vitro, EZH1/2 was demonstrated to be essential for oocyte development during meiosis prophase I in mice. Activity inhibition or gene knockout of EZH1/2 resulted in cell apoptosis and a reduction in oocyte numbers within embryonic ovaries. By observing the expression of some meiotic marker protein (γ-H2AX, diplotene stage marker MSY2 and synapsis complex protein SCP1), we found that function deficiency of EZH1/2 resulted in failure of DNA double-strand breaks (DSBs) repair and break of meiotic progression in fetal mouse ovaries. Moreover, Ezh1/2 deficiency led to the suppression of ATM (Ataxia Telangiectasia Mutated kinase) phosphorylation and a decrease in the expression of key DNA repair proteins Hormad1, Mre11, Rad50, and Nbs1 in fetal mouse ovaries, underscoring the enzyme's pivotal role in initiating DNA repair. RNA-seq analysis revealed that Ezh1/2-deletion induced abnormal expression of multiple genes involved into several function of oocyte development in embryonic ovaries. Knockout of Ezh1/2 in ovaries also affected the levels of H3K9me3 and H4K20me2, as well as the expression of their target genes L3mbtl4 and Fbxo44.
Conclusions: our study demonstrated that EZH1/2 plays a role in the DSBs repair in oocyte meiosis prophase I via multiple mechanisms and offers new insights into the physiological regulatory role of histone modification in fetal oocyte guardianship and female fertility.
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http://dx.doi.org/10.1186/s40659-024-00564-4 | DOI Listing |
Sci Rep
January 2025
The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, No. 26 Heping Road, Harbin, 150040, Heilongjiang, China.
Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder affecting women of childbearing age, and we aimed to reveal its underlying molecular mechanisms. Gene expression profiles from GSE138518 and GSE155489, and single-cell RNA sequencing (scRNA-seq) data from PRJNA600740 were collected and subjected to bioinformatics analysis to identify the complex molecular mechanisms of PCOS. The expression of genes was detected by RT-qPCR.
View Article and Find Full Text PDFJ Obstet Gynaecol Res
January 2025
Reproductive Sciences and Technology Research Center, Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Objective: To evaluate the efficacy of a microfluidic culture system supplemented with follicular fluid meiosis-activating sterol (FF-MAS) on the maturation of immature oocytes in patients with polycystic ovarian syndrome (PCOS).
Methods: A total of 438 germinal vesicle oocytes from 163 PCOS patients were included. Oocytes were divided into five groups: (1) cultured in static drops without FF-MAS, (2) cultured in static drops with FF-MAS, (3) cultured in a microfluidic device without FF-MAS, (4) cultured in a microfluidic device with FF-MAS for the first 2 h, and (5) cultured in a microfluidic device with FF-MAS for 24 h.
Reproduction
January 2025
D Cohen, Fundación IBYME. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)., Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.
Artificial oocyte activation (AOA) with Ca2+ ionophores is an experimental procedure that benefits patients who fail to obtain fertilized eggs. However, the impact of non-physiological Ca2+ increases on cellular events involved in egg-embryo transition and early development remains poorly understood. Using the mouse model, this study compares common Ca2+ ionophore protocols applied in clinical practice - one or two exposures to A23187 or a single exposure to ionomycin - focusing on embryonic development and cellular events associated with egg activation.
View Article and Find Full Text PDFClin Transl Med
January 2025
State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China.
Background: Numerous pathogenic variants causing human oocyte maturation arrest have been reported on the primate-specific TUBB8 gene. The main etiology is the dramatic reduction of tubulin α/β dimer, but still large numbers of variants remain unexplained.
Methods: Using microinjection mRNA and genome engineering to reintroduce the conserved pathogenic missense variants into oocytes or in generating TUBB8 variant knock-in mouse models, we investigated that the human deleterious variants alter microtubule nucleation and spindle assembly during meiosis.
bioRxiv
January 2025
MCB Graduate Program, Cell Biology, and Biochemistry, Brown University, 70 Ship St., Box G-E4, Providence, RI 02903, USA.
Female reproductive senescence results from the regulated depletion of a finite pool of oocytes called the ovarian reserve. This pool of oocytes is initially established during fetal development, but the oocytes that comprise it must remain quiescent for decades until they are activated during maturation in adulthood. In order for developmentally competent oocytes to populate the ovarian reserve they must successfully initiate both meiosis and oogenesis.
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