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Studie enthüllt neuen Mechanismus für die Langlebigkeit von Eizellen

von NFI Redaktion

Egg cells are immature eggs that develop before birth in almost all female mammals. The reproduction of future generations depends on this limited cell reserve surviving for many years without damage. In mice, this can be a period of up to eighteen months, while in humans, it can be almost half a century, the average time between birth and menopause. How the cells achieve this remarkable longevity has long been a question.

Researchers at the Center for Genomic Regulation (CRG) in Barcelona have discovered a new mechanism that explains how egg cells remain flawless for decades without succumbing to the wear and tear that would cause other cell types to fail. The results were published today in the journal Cell and present a new frontier for exploring the unknown causes of infertility.

The researchers examined protein aggregates, which are lumps of misfolded or damaged proteins. In the majority of cell types, these toxins are managed by dismantling them with special enzymes, or by splitting them between two cells during division. However, egg cells, given their long lifespan, cannot eliminate these toxic substances through cell division. Their strategy is to minimize metabolic activity and contain these toxic substances, making them particularly vulnerable to the effects of misfolded or damaged proteins.

Dr. Elvan Böke, Group Leader of the Oocyte Biology and Cell Rest Program at the Center for Genomic Regulation, explained, „Unlike the tens of thousands of studies on protein aggregation in neurons, the way in which mammalian egg cells deal with protein aggregation is essentially unexplored, although they face the same problem of being long-lived and not dividing.“

Patrolling ‚Cleanup Crews‘

Dr. Böke’s team, under the leadership of Dr. Gabriele Zaffagnini, discovered special structures in the egg cells, which they called EndoLysosomal Vesicular Assemblies (ELVAs). These structures capture and hold protein aggregates, rendering them harmless. They are viewed as „super organelles“ because they are a network of different types of cell components working together as one unit.

The study revealed a crucial moment during the egg cell’s maturation phase, when an egg cell transforms into a mature one and prepares for ovulation and potential fertilization. At this stage, ELVAs move to the cell surface, breaking down protein aggregates and effectively cleaning the cytoplasm. This is the first observation of the unique strategy egg cells use to eliminate protein aggregates.

Protein Aggregates can Contribute to Infertility

Understanding how egg cells remain healthy and why these strategies fail with age is crucial in uncovering unresolved causes of infertility and opening up new treatment options. The study’s results suggest that the presence of protein aggregates could affect the quality of both the egg cell and embryo.

When the researchers prevented ELVAs from breaking down protein aggregates during the egg cell’s maturation process, it led to the formation of defective egg cells. Additionally, interfering with embryonic inheritance of aggregated proteins resulted in 60% failure in very early developmental stages.

The study paves the way for future research beyond the realm of reproduction by proposing that ELVA-like compartments may also exist in neurons and other cell types. The study was conducted by the Center for Genomic Regulation, and it is referenced in the journal Cell.

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