Immature eggs remain healthy in a dormant state for decades

Immature human eggs, also called oocytes, skip a critical metabolic reaction to generate energy, which, in turn, also causes cell wear. With this strategy they manage to stay healthy in a dormant state for decades, according to a study by the Spanish Center for Genomic Regulation (CRG).

This research, published this Wednesday in the journal Nature, explains how oocytes do not follow the conventional mechanism of cells to generate energy, thus avoiding the wear and tear that this system entails and managing to remain healthy for up to 50 years, without losing their reproductive capacity .

“As a long-term maintenance strategy, it's like putting the engine in neutral; this represents a new paradigm never seen before in animal cells”, highlighted CRG researcher Aida Rodríguez, first author of the study.

Human eggs are first formed in the ovaries during fetal development, passing through various stages of maturation.

During the early stages, immature eggs remain in a state of cellular arrest and remain inactive for up to 50 years in the ovaries.

Like all eukaryotic cells, oocytes contain mitochondria, the cell's batteries or engine, which they use to generate energy for their needs during this latency period.

Using a combination of live imaging, proteomic techniques - to study proteins on a large scale - and biochemistry, the authors of the study found that the mitochondria in human oocytes and frogs of the xenopus genus use alternative pathways to generate energy never before seen in other types of animal cells.

An enzyme complex known as complex I is the usual entry point that initiates the reactions necessary to generate energy in the mitochondria, but in oocytes, however, this mechanism is practically absent.

Because oocytes bypass this complex I metabolic activity, they also avoid its negative consequences, such as the creation of harmful molecules that can accumulate, damage DNA, and cause cell death, thereby remaining healthy for decades.

According to the study authors, the research explains why some women with complex I-linked mitochondrial conditions, such as Leber hereditary optic neuropathy, do not experience reduced fertility.

The findings could also lead to new strategies to help preserve ovarian reserves in patients undergoing cancer treatment.

The researchers plan to continue this line of research and discover the source of energy used by oocytes during their long latency stage in the absence of complex I, to better understand female fertility and therapeutic possibilities.

"One in four cases of female infertility is unexplained, which points to a large knowledge gap in our understanding of female reproduction," said the lead author of the study and head of the Cell Biology and Development group at the CRG, Elvan Boke.

Thus, one of the objectives "is to discover strategies (such as the lack of complex I) that oocytes use to stay healthy for many years to discover why these strategies finally fail with advanced age," said Dr. Böke.