Friday, June 06, 2025

Lack of iron (iron deficiency in pregnannt mice) induces male mice to develop ovaries

A dream come true for transgender females? Just kidding!

"A surprising finding from researchers in Japan has shown how an environmental factor can influence the development of sex organs in unborn mice. The discovery challenges the longstanding belief that sex is determined purely by genetic factors. ..."

From the abstract:
"Ferrous iron (Fe2+) is essential in all eukaryotic cells for various oxidoreductase reactions, including the demethylation of DNA and proteins. Histone demethylation is required for normal epigenetic regulation of the Y-chromosomal sex-determining gene Sry in developing gonads during male sex determination.
Here we investigate the potential connection between iron metabolism, histone demethylation and sex determination in mammals.
We found that Fe2+-producing pathways are substantially activated in mouse embryonic gonads during the sex-determining period. Chelation of iron in cultured XY gonads reduced the level of KDM3A-mediated H3K9 demethylation of Sry, mostly abolished Sry expression and caused the gonads to express ovarian markers.
In vivo, conditional deletion of the gene Tfrc—which is required for iron incorporation—in fetal XY gonadal somatic cells, or acute pharmaceutical suppression of available iron in pregnant mice, resulted in male-to-female gonadal sex reversal in a proportion of offspring, highlighting the pivotal role of iron metabolism in male sex determination.
Finally, long-term feeding of pregnant mice with a low-iron diet, when combined with a heterozygous variant of Kdm3a that by itself has no observable effect, suppressed Sry expression and caused male-to-female sex reversal in some of the progeny, revealing a connection between maternal dietary iron and fetal developmental outcomes."

Lack of iron in pregnancy affects mouse sex organs

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