For the first time, they have managed to convert a male mammal into a female during gestation using an environmental factor.

A team of Japanese researchers from Osaka University has achieved something never before seen: inducing male-to-female sex reversal in mice. ABC spoke with the team leader, biologist Makoto Tachibana, who explains that "to our knowledge, this is the first demonstration that an environmental factor can influence sex determination in a mammal ." He further notes that "a key implication is that the nutritional status of the pregnant mother, specifically iron availability, can influence the sexual development of her offspring." These findings highlight the close relationship between genetics and environmental factors.

The study, published in the journal Nature, details that the complete sex reversal was caused by the inactivation of the SRY gene, located on the Y chromosome, which acts as a switch to trigger the production of hormones responsible for male sexual characteristics, including the formation of the testes.

Tachibana clarifies that " the gene responsible for the onset of male development is activated by a specific enzyme called KDM3A. This enzyme requires iron to function , but when there is a severe deficiency—in the experiment, a 60% reduction was achieved—the enzyme cannot operate correctly, the gene stops being activated, and male development does not occur."

To achieve this, they blocked the entry of iron into the gonadal cells of male embryos. As a result, six of 39 genetically male offspring were born with two ovaries instead of testes , and another offspring was born intersex, meaning with both sex organs. In another series of experiments, they fed a group of pregnant mice an iron-poor diet, and five of 72 XY embryos developed female sex organs.

The scientist emphasizes that "the greatest challenge in this study was inducing a state of severe anemia in the fetus" and adds that "both genetics and epigenetics are essential and work together to regulate development." Researchers outside this work agree: the impressive results show the importance of genetics and epigenetics in the uterus, which studies how metabolic and external factors can "turn on" or "turn off" certain genes, affecting the sexual development of these rodent offspring.

When asked whether these offspring will be able to produce offspring, Tachibana responds that they don't know yet , and that it also remains to be investigated whether similar phenomena could apply to other animals, including humans. However, the study could have great potential in research into genetic diseases. "The first step is to determine whether the same mechanism operates in humans. This will be crucial for evaluating its potential implications for human diseases," he concludes.