A group of scientists from the Cancer Research Center has identified the cause of a type of female infertility: it is a variant of the HSF2BP gene which, in contact with another protein, causes defects in the gestation process of reproductive cells (gametes).

Approximately 12% of couples of childbearing age worldwide are infertile. In the case of women, one of the main causes is primary ovarian failure, which affects between 1% and 3% of women under 40 years of age, as explained by the Center for Scientific Research (CSIC), a research collaborator with the University of Salamanca.

However, the causes and origins that lead to this disease are still difficult to identify, although it is believed that in many cases the reason may be genetic.

It would be the case of this type of specific female infertility, which arises with the mutation of a gene. According to the work, published in the magazine Bioimedina eLife, the BRME1 protein (unknown until now) strongly interacts with the HSF2BP protein, stabilizing it. That contact between the two, in the end, causes a series of defects in meiotic cell division during the gestation of gametes – that is, reproductive cells – causing premature ovarian failure.

In short, what it does is affect the process of meiosis, fundamental in human reproduction. But, What exactly is meiosis? “It is a type of specialized cell division, characteristic of organisms that produce gametes, to carry out sexual reproduction “, explains the director of the investigation, Alberto M. Pendás.

This division, moreover, is reductive. That is daughter cells are created with half the chromosomes of the initial cell (diploid cell), thus joining the paternal and maternal chromosomes and ensuring genetic diversity.

New insights

“The identification and characterization of the BRME1 protein, as well as the in-depth characterization of the meiotic defects of the HSF2BP mutants, provide important new insights into the molecular mechanisms that govern a new and unknown essential protein for meiotic recombination “, says researcher Natalia Felipe-Medina, first author of the work.

The study research and testing was done in genetically modified mice, which carry both the human infertile variant in the HSF2BP gene and the deletion of the HSF2BP and BRME1 gene. “In this way, they were able to verify that the mice deficient in the HSF2BP gene were sterile due to meiotic defects almost identical to the mice lacking the BRME1 gene, while the humanized mice with the HSF2BP gene they had subtle alterations in meiotic recombination, which caused a decrease in their fertility “, concludes the CSIC in a statement.