new ways of understanding the harmful effects of chemotherapy

THE ESSENTIAL

  • Almost 3.3 million French people are directly affected by infertility.
  • This can affect both men and women and has been steadily increasing in recent years.

Infertility is a public health problem affecting millions of couples in France, who are particularly vulnerable to chemotherapy. “Understanding the mechanisms behind these adverse effects is a priority to better prevent them and restore fertility in cancer survivors,” explain researchers from Inserm, CNRS and the University of Clermont Auvergne.

“reduce renewal”

So, in a new study published in the journal Advanced Science, they took an interest in a receptor found on male germ cells at the origin of gametes. called “TGR5”.

To better understand its role, scientists exposed mice to a chemotherapy drug called busulfan. They then showed that chemotherapy in healthy mice leads to the death of part of the germ cells and thus impairs their fertility. “The fact that the still undifferentiated germ cells are affected is particularly problematic because we are attacking the reserve of gamete-producing cells. This can reduce their renewal and contribute to infertility after chemotherapy.” emphasizes David Volle, one of the authors of the study.

In contrast, in genetically engineered mice that lacked TGR5 receptors, the effects of chemotherapy on germ cells were attenuated. This resulted in an accelerated return of fertility in these busulfan-treated mice compared to control mice.

Molecular Mechanisms

“Our study has therefore led to a better understanding of the molecular mechanisms involved in the deleterious effects of chemotherapy on germ cells and fertility. Indeed, these results indicate that TGR5 receptors play an important role,” adds David Volle.

In the longer term, the goal would be to develop methods to specifically modulate the activation of TGR5 receptors within germ cells to protect them and restore fertility after chemotherapy. The idea would also be to evaluate whether these data can be extrapolated to other pathological contexts where the activity of TGR5 receptors could be modulated, such as B. obesity or diabetes, pathologies known to affect fertility.

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