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This research addresses a central issue in fertility: the increase in chromosomal abnormalities in eggs with age. These errors, which cause implantation failure and miscarriages, are the main reason for the decline in IVF success rates after age 35. The work, led by the Max Planck Institute and the startup Ovo Labs, proposes a direct correction of this defect by restoring the levels of a protein essential for proper cell division.
Egg aging: a question of cohesion
The origin of the problem lies in meiosis, the specific cell division that prepares the egg for fertilization. To form a healthy embryo, the 23 pairs of chromosomes must separate in a perfectly symmetrical manner. With age, this precision mechanism becomes dysregulated. Chromosomes, normally linked at their center, tend to dissociate prematurely.
This chaotic separation leads to egg cells containing an abnormal number of chromosomes, a condition called aneuploidy. It is the source of many difficulties. British data illustrate this challenge: the live birth rate per transferred embryo drops from 35% in women under 35 to just 5% for those aged 43-44. The search for a solution therefore motivated the in-depth study of the cellular mechanisms involved.
The team identified that the failure is correlated with a decrease in a specific protein: Shugoshin 1. Its role is crucial: it acts as a molecular glue maintaining the integrity of chromosome pairs until the precise moment of their separation. As they age, egg cells produce less of this protein, weakening the chromosomal structure and paving the way for errors. This discovery formed the starting point for the therapeutic approach tested.
A targeted intervention to restore function
The developed strategy is deceptively simple: reintroduce the missing protein directly into the egg cell. After conventional retrieval in a clinic, the eggs receive a microinjection of Shugoshin 1, aimed at restoring concentrations similar to those observed in younger women. This operation is performed in the laboratory, before fertilization by intracytoplasmic sperm injection.
Preliminary results, detailed in a preprint on bioRxiv, are encouraging. In a sample of eggs donated by patients, the proportion showing chromosomal alignment defects decreased from 53% in the untreated group to 29% after treatment. Even in women over 35, a trend towards improvement was observed (the defect rate dropping from 65 to 44%), although the study needs to be expanded to statistically confirm this point.
However, the researchers temper the enthusiasm by reminding of the preliminary nature of these data. The next step will be to verify whether this improvement in egg quality concretely translates into the formation of more viable embryos and, ultimately, an increase in healthy births. Discussions are underway with health authorities to consider a clinical trial.
To go further: What is aneuploidy?
Aneuploidy refers to an abnormality in the number of chromosomes in a cell. Normally, human cells, except gametes, have 46 chromosomes organized into 23 pairs. A healthy egg or sperm contains only 23, one from each pair. During fertilization, the two sets combine to reform the 46 chromosomes.
If a gamete brings an incorrect number of chromosomes, the resulting embryo will be aneuploid. For example, an egg containing 24 chromosomes (with a duplicate chromosome 21) will result, after fertilization, in an embryo with 47 chromosomes, including three copies of chromosome 21. This specific situation is the origin of Down syndrome (trisomy 21).
Aneuploidy is a major cause of early pregnancy failure. Most aneuploid embryos do not implant in the uterus or cause a spontaneous miscarriage in the first trimester. The frequency of these errors increases exponentially with maternal age, due to the aging of the eggs stored since birth.