Iron regulates sexual development in males

MADRID (EFE).— A lack of iron in pregnant mice can cause embryos with XY chromosomes to develop ovaries, according to a study led by Osaka University (Japan) and published in the journal Nature. The research found that iron deficiency alters the expression of the Sry gene, responsible for testicular development.

“Factors in the uterine cellular environment regulate Sry gene expression,” the journal summarizes. When iron levels were reduced to 40%, “Sry expression was largely suppressed,” and XY gonads began to show genetic signatures typical of ovaries. The experiment involved administering an iron-depleting drug to pregnant mice over five key days. Of the 72 offspring with XY chromosomes, four developed two ovaries, and one had one ovary and one testis. “In none of the experiments were abnormalities observed in the offspring of mothers with normal iron levels,” the report states.

The researchers also studied the KDM3A enzyme, which is essential for activating the Sry gene and depends on iron for its function. By introducing a mutation that disables this enzyme, "sex reversal from male to female was recorded in two of the 43 XY offspring," the authors explained.

An explanatory article from Duke University points out that, unlike other animals, "mammals develop in a controlled uterine environment," where sex is genetically determined. However, this study suggests that "maternal environmental factors derived from nutrition or metabolism may influence embryonic development."