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Potential new diagnostic markers predict the successful and efficient development of mammalian egg cells

Potential new diagnostic markers predict the successful and efficient development of mammalian egg cells

 


Researchers at the Center for Genome Regulation (CRG) in Barcelona have identified potential new diagnostic markers that predict the successful and efficient development of mammalian egg cells. Findings could pave the way for the production of artificial egg matrix cells in the lab, where researchers study the causes and treatments of infertility and test the effects of drugs and chemicals on female reproduction. Helps to.The study is published at The EMBO Journal..

Humans have 23 pairs of chromosomes.22 pairs will be shared and 23 pairs will be shared between men and womenrd The pair is a sex chromosome. Men usually have an X and a Y chromosome, while women have two X chromosomes. This presents a potential problem with female cellular mechanisms as the two active X chromosomes produce overdose gene products. It is fatal to embryonic development or causes cancer in adulthood. To avoid this scenario, female cells inactivate one X chromosome by turning off the gene and compressing it.

Little is known about how X-chromosome inactivation affects germ cell development. In mammals, oocytes develop from germ cells, progenitor cells that migrate from early embryonic tissue to the developing gonads. Next, germ cells undergo meiosis. This is an important chromosomal rearrangement process and is involved in the genetic uniqueness of individual germ cells. Germ cells mature and eventually turn into functional sperm or oocytes.

To address this question, researchers at the Center for Genome Regulation (CRG) have built the X Chromosome Reporter System (XRep). This is a tool that allows you to study how the shape of chromosomes changes over time during germ cell development. In vitro..

Using female mouse cells, this method revealed a carefully organized effect on the X chromosome “yo-yo.” When one X chromosome is temporarily inactivated and then reactivated, the germ cell enters meiosis and becomes an egg cell compared to a germ cell that has never turned the X chromosome “off and on”. 4x more efficient to convert. In comparison, germ cells that could not inactivate the X chromosome or reactivated too quickly showed aberrant gene expression and cell differentiation patterns.

The study also found that cells with two active X chromosomes divide faster and easily return to a pluripotent state. According to the authors, these features resemble human germ cell tumors that form germ cells that are lost during migration to the gonads or that fail to differentiate properly in the testis or ovary. Researchers speculated that the correct sequence of X-chromosome inactivation and reactivation is an indicator of normal germ cell differentiation. The researchers say more research is needed to see if the abnormal X-chromosome condition is a diagnostic indicator, or if it can cause cellular abnormalities.

Our findings have important implications for reproductive research, as XRep can be used to assess the state of the X chromosome of a cell in real time, helping to identify and isolate germ cells with a high success rate of conversion to oocytes. I have. “


Dr. Bernhard Peyer, CRG Group Leader and Senior Author of Research

“Human oocytes have never been completely produced In vitro..Monitoring the X-chromosome status inside In vitro Therefore, germ cell differentiation may be a way to optimize the protocol for producing high quality human eggs in the laboratory. Human eggs for research are currently only available from egg donors and are difficult to obtain and difficult to obtain as they are used primarily for reproductive purposes. In vitroTherefore, the human eggs produced may provide unlimited resources to study the causes and treatments of infertility and to test the safety of drugs and chemicals for female reproduction. ” Dr. Payer concludes.

Dr. Moritz Bauer, co-lead author of this study, adds: Therefore, we need to stop seeing female development through the lens of male cells. It will help to understand the progression of gender-specific illnesses. “

Source:

Journal reference:

Severino, J. , et al. (2022) Controlled X-chromosome activation dynamics define the potential for meiosis in in vitro germ cells of female mice. EMBO Journal. doi.org/10.15252/embj.2021109457..

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