While infertility affects one in four couples in France, French researchers have just understood why chemotherapy reduces the chances of conceiving a child, in both men and women.
- Nearly 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, on which chemotherapy has particularly deleterious effects. “Understanding the mechanisms behind these negative effects is a priority in order to better prevent them and restore fertility in cancer survivors”, explain researchers from Inserm, CNRS and Clermont Auvergne University.
“Reduce renewal”
In a new study published in the journal Advanced Science, they were therefore interested in a receptor found on the male germ cells at the origin of gametes, called “TGR5”.
To better understand its role, scientists exposed mice to a chemotherapy agent called busulfan. They then showed that chemotherapy induces the death of part of the germ cells in healthy mice, thus affecting their fertility. “The fact that it is the germ cells, which are still undifferentiated, which are affected is particularly problematic because we are affecting the reserve of cells producing gametes. This can reduce their renewal and contribute to post-chemotherapy infertility”, underlines David Volle, one of the authors of the study.
In contrast, in mice that were genetically engineered to lack 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 provided a better understanding of the molecular mechanisms involved in the deleterious impacts of chemotherapy on germ cells and fertility. Indeed, these results demonstrate that TGR5 receptors play an important role”, adds David Volle.
In the longer term, the objective would be to develop methods to modulate the activation of TGR5 receptors in a targeted manner within germ cells, in order to protect them and restore fertility after chemotherapy. The idea would also be to assess whether these data can be extrapolated to other pathological contexts where the activity of TGR5 receptors could be modulated, such as obesity or diabetes, pathologies known to impair fertility.
