Most of us think gender is set by genes—if a baby has XY chromosomes, they’ll be a boy and XX will be a girl. But researchers have now found something surprising: a mother’s iron levels during pregnancy might actually override that genetic setup. In mice, when the pregnant mother didn't have enough of a specific type of iron—called ferrous iron (Fe²⁺)—some genetically male embryos developed as female.

Ferrous iron plays a key role in helping certain enzymes do their job, especially during early development. One enzyme, KDM3A, is needed to remove tiny chemical markers on DNA, a process known as histone demethylation. This cleanup is essential to activate a gene called Sry, which tells the body to start forming testes. Without enough ferrous iron, KDM3A can’t work properly, and Sry stays silent. When that happens, even an embryo with XY chromosomes can start growing ovaries instead of testes.

Researchers found that during the time when gender is being decided in the womb, mouse embryos activate the body’s iron pathways in a big way. But when scientists blocked iron in different ways—removing iron-transport genes, using iron-blocking drugs, or feeding mice a low-iron diet—some male embryos didn’t develop as male. In one experiment, even a slight gene change combined with low iron led to gender reversal in some baby mice.

This research shows that gender development isn't just about DNA. Even something as basic as iron in the mother's diet can influence how a baby develops.

Citation:

Okashita, N., Maeda, R., Kuroki, S. et al. 

Maternal iron deficiency causes male-to-female se reversal in mouse embryos. 

Nature 643, 262–270 (2025).  

PMID: 40468068