Maternal Iron Deficiency Causes Sex Reversal in Male Mouse Embryos, Study Finds.

The long-standing belief that sex determination in mammals is guided solely by genetic factors is now being challenged. In a recent Nature study, scientists from Osaka University, led by Makoto Tachibana, discovered that maternal iron deficiency can significantly impair testis development in genetically male mouse embryos—resulting in partial or complete sex reversal.

Typically, the presence of the Y chromosome and activation of the Sry gene initiates male development, leading to the formation of testes. In its absence, ovaries form by default. During early development, the Sry gene is epigenetically silenced by methyl groups. For sex determination to proceed, these chemical markers must be removed. Previous work by Tachibana’s team identified the enzyme KDM3A as essential in removing these methyl groups. Importantly, this enzyme’s function depends on iron.

To explore this connection further, the researchers engineered mice lacking a gene crucial for iron storage in gonadal cells during the sex-determining phase. In these XY embryos, DNA methylation of the Sry gene increased significantly, reducing its activity. As a result, SRY protein levels dropped to half of those in embryos with normal iron levels. Upon examining the reproductive organs, researchers found that 7 out of 39 genetically male embryos developed ovaries instead of testes.

In a second experiment, pregnant mice were given iron chelators during the sex determination window, leading to systemic iron deficiency. This intervention caused three out of 72 XY embryos to develop ovotestes—gonads containing both male and female cell types—indicating a disruption in normal sex development. The researchers were able to partially reverse this by overexpressing the Sry gene in the iron-deficient embryos, which reduced the prevalence of female-type somatic cells.

Interestingly, when iron deficiency was induced solely through diet, sex reversal occurred only in embryos that were also missing one copy of the Kdm3a gene. This suggests that genetic vulnerability, combined with low iron levels, is necessary to trigger the sex change.

These findings not only broaden our understanding of sex determination but also open the door to examining how other maternal metabolic conditions may influence fetal development. Whether similar mechanisms are at play in humans remains a critical question for future research.

Source:https://www.the-scientist.com/maternal-iron-deficiency-can-trigger-sex-reversal-in-mouse-embryos-73070

This is non-financial/medical advice and made using AI so could be wrong.