Inhibition of EED activity enhances cell survival of female germline stem cell and improves the oocytes production during oogenesis in vitro

by Selleckchem | Aug 06 2023

Ovarian organoids, based on female germline stem cells (FGSCs), are nowadays widely applied for reproductive medicine screening and exploring the potential mechanisms during mammalian oogenesis. However, there are still key issues that urgently need to be resolved in ovarian organoid technology, one of which is to establish a culture system that effectively expands FGSCs in vitro, as well as maintaining the unipotentcy of FGSCs to differentiate into oocytes. Here, FGSCs were EED226 treated and processed for examination of proliferation and differentiation in vitro. According to the results, EED226 specifically increased FGSC survival by decreasing the enrichment of H3K27me3 on Oct4 promoter and exon, as well as enhancing OCT4 expression and inhibiting P53 and P63 expression. Notably, we also found that FGSCs with EED226 treatment differentiated into more oocytes during oogenesis in vitro, and the resultant oocytes maintained a low level of P63 versus control at early stage development. These results demonstrated that inhibition of EED activity appeared to promote the survival of FGSCs and markedly inhibited their apoptosis during in vitro differentiation. As a result of our study, we propose an effective culture strategy to culture FGSCs and obtain oocytes in vitro, which provides a new vision for oogenesis in vitro.

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The passage you provided describes a study that investigates the use of EED226, a compound that inhibits the activity of a protein called EED, in the culture of female germline stem cells (FGSCs) for the purpose of oocyte production. The researchers aimed to address the key challenge of expanding FGSCs in vitro while maintaining their ability to differentiate into oocytes.

The results of the study showed that treatment with EED226 had several effects on FGSCs. Firstly, it increased the survival of FGSCs by reducing the enrichment of a histone modification called H3K27me3 on the Oct4 gene promoter and exon regions. This reduction in H3K27me3 levels was associated with enhanced expression of OCT4, a transcription factor important for maintaining stem cell properties. Additionally, the treatment with EED226 inhibited the expression of two other proteins, P53 and P63, which are known to be involved in regulating cell apoptosis.

Importantly, the researchers observed that the FGSCs treated with EED226 had an increased capacity to differentiate into oocytes during in vitro oogenesis. Furthermore, these resulting oocytes exhibited a lower level of P63 expression compared to the control group during early stages of development. This finding suggests that the inhibition of EED activity promoted the survival of FGSCs and suppressed their apoptosis during the differentiation process.

Based on these findings, the researchers propose that the use of EED226 as part of a culture strategy could effectively expand FGSCs in vitro and facilitate the generation of oocytes. This study provides new insights into the field of in vitro oogenesis and offers a potential approach for reproductive medicine screening and understanding the mechanisms involved in mammalian oocyte development.