Turns out, it’s not just chromosomes that determine sex during fetal development. While we’ve long believed that an embryo’s sex is locked in from the moment sperm meets egg (XX for female, XY for male) new research suggests things might not be so fixed. In fact, all humans start out with the same potential. For the first six weeks of development, we all carry the foundation to become either sex. It’s only around week seven that the body switches on a biological program to form either testes or ovaries.
That in-between period has raised an intriguing question: Could environmental factors, like a nutrient deficiency, interfere with that genetic programming?
A recent Nature study from researchers at Osaka University suggests that it can — at least in mice. The team found that low iron levels in pregnant mothers can override genetic sex, turning male (XY) embryos into females (XX). The study adds to a growing body of research showing how complex and sensitive sex development really is.
Role of Iron in Sex Development
People born with a mix of sex characteristics, such as individuals with XY chromosomes who develop ovaries, aren’t new to science. Many of these cases are linked to variations in a gene called SRY, which is normally responsible for triggering testis formation. If SRY activates properly, testes develop; if not, ovaries form by default. This process kicks off a chain of events that shapes sexual anatomy through hormone signals.
Until now, it was thought that this process happened in a kind of biological vacuum, protected from outside influence. But the Osaka researchers had a clue that iron might matter. They’d previously shown that SRY is activated by an enzyme called Kdm3a, which requires iron to work.
That led to a new question: Could iron deficiency disrupt sex development?
Read More: Everything You Need to Know About Iron Supplements
Decoding Iron Impact
To test their idea, the team used multiple experiments. In one experiment, they removed iron from lab-grown gonads (glands that produce sex hormones) of XY embryos. The result: SRY was silenced, and the cells started expressing ovarian markers.
Then, they genetically disabled the ability of fetal gonadal cells to absorb iron. In this group of 39 XY embryos, 6 developed ovaries and 1 had mixed traits — an ovary and a testis. That’s about 18 percent showing full or partial sex reversal.
In another experiment, pregnant mice were treated with a pharmaceutical that depletes iron. Of 41 XY offspring, 6 had two ovaries and 3 more showed mixed gonads.
Finally, they tested whether maternal diet alone could trigger the effect. Mice fed a low-iron diet gave birth to genetically male offspring that developed with typical male anatomy — unless those embryos carried a harmless mutation in the Kdm3a gene. In that case, 2 out of 43 XY offspring developed female-typical sex organs. That finding reinforced the idea that iron plays a role in SRY activation, particularly when the underlying genetic pathway is altered.
What It Means for Pregnancy
This is the first known case of a dietary mineral influencing sex development through epigenetics, chemical markers that regulate how genes behave. Iron is essential for one of the key enzymes in this process. If it’s missing, the machinery that activates male development can break down.
The genetically male mice with ovaries appeared healthy for at least eight weeks, but whether they could reproduce wasn’t studied. There’s no evidence that the same mechanism occurs in humans — but the possibility raises important questions.
Iron deficiency is common in pregnancy, especially in the third trimester. While the recommended daily intake is 27 milligrams, many women don’t get enough, putting them at risk for anemia, miscarriage, and infection.
Whether iron deficiency can influence fetal sex in humans remains unknown. But the research suggests it’s worth investigating and highlights how the environment inside the womb can shape a fetus even more than we already understood.
This article is not offering medical advice and should be used for informational purposes only.
Read More: Debunking Myths Around Predicting the Sex of Your Baby
Article Sources
Our writers at Discovermagazine.com use peer-reviewed studies and high-quality sources for our articles, and our editors review for scientific accuracy and editorial standards. Review the sources used below for this article:
American College of Obstetricians and Gynecologists: Nutrition During Pregnancy
Nature: Maternal iron deficiency causes male-to-female sex reversal in mouse embryos
Having worked as a biomedical research assistant in labs across three countries, Jenny excels at translating complex scientific concepts – ranging from medical breakthroughs and pharmacological discoveries to the latest in nutrition – into engaging, accessible content. Her interests extend to topics such as human evolution, psychology, and quirky animal stories. When she’s not immersed in a popular science book, you’ll find her catching waves or cruising around Vancouver Island on her longboard.
