Is your heart female? Your liver male? New research suggests that the stem cells our organs are made of “know” whether they are “male” or “female,” and that this gender bias could impact the development and behavior of organs.
The findings, published in the journal Nature, may explain why some diseases, such as certain cancers, are more prevalent in one gender that the other.
The results could also have implications for how men and women respond to the same treatment.
Until now, it has been assumed that, apart from the reproductive system, organs such as the kidneys or the pancreas are the same in both males and females, although circulating hormones cause them to function differently.
New research in fruit flies, however, has discovered a set of genes, also present in mammals, that may underlie differences between “male” and “female” organs, quite apart from any hormonal effects.
Researchers at the Medical Research Council’s (MRC) Clinical Sciences Centre, based at Imperial College London, in the UK, studied stem cells in the intestines of fruit flies to find out whether cells of organs other than the reproductive system “know” their sex, and if so, does it matter?
By turning certain genes “on” and “off” in these cells, they were able to tailor the cells to be more “male” or “female.” Masculinizing or feminizing the stem cells altered the extent to which the cells multiplied, with feminized cells better able to do so.
First author Dr. Bruno Hudry explains: “If we take a female fly and masculinize the stem cells in the adult intestine, within 3 weeks the gut shrinks to the smaller, male-like size.
The researchers also found that the female intestine was more prone to genetically induced tumors. They speculate that females need to be more adaptable to cope with reproduction, but this may be what makes them more susceptible to tumors.
The gender of the intestine appears to be actively maintained, which means it is also reversible. Dr. Hudry told Medical News Today:
“Modulating the activity of these genes specifically in stem cells (without affecting overall organismal sex or hormonal sex) can lead to sexual identity reversal: female stem cells behaving like males or male stem cells acting like females.”
By manipulating the genes responsible for this sexual identity, the scientists believe they could alter the way the organs behave without affecting their development or the circulating hormones.
This newly discovered mechanism may mean that every cell in the fly has a sexual identity, notes lead author Dr. Irene Miguel-Aliaga.
Dr. Des Walsh, also of MRC, notes that the study deepens our understanding of the underlying factors that make male and female physiology different.
MNT asked Dr. Hudry whether, if a person is female, for example, the entirety of that person’s organs would be female, or might there be some male organs or organs with male traits?
He replied that the results emphasize the problem of sex being defined in binary terms, in other words, simplified to male and female.
He went on to explain that sex can be defined on different levels: chromosomal sex, cellular sex, tissue sex and organismal sex. Just as people may have different levels of male and female hormones, creating a kind of male-female continuum, so too with cellular sex. Depending on genetic activity, he explained, stem cells can present a male or female identity.
He added: “Mosaicism can exist at cellular level: XX individuals could have some cells behaving like XY cells. So yes, females can have organs presenting male traits because of sexual cellular mosaicism.”
Dr. Hudry told MNT:
“This study shows that there is a wider spectrum than just two sexes. You can be chromosomally, hormonally or phenotypically female but still having some specific adult stem cells (here the stem cells of the intestine) acting like male. So it is hard to say if someone is “really” male or female. Some people are simply a mosaic of male and female cells within a phenotypically ‘male’ or ‘female’ body.”
Regarding implications for improving treatment options in the future, MNT asked Dr. Hudry how this information, if confirmed in humans, could affect interventions such as transfusions and organ donations.
He explained that sex needs to be analyzed at all levels, from chromosomes, cells and organs to whole organisms, making cellular sex of stem cells a potentially significant factor in stem cell therapy and regenerative medicine.
The interaction between the sex of the donor cells, the sex of the host and the type of stem cells transplanted, he said, could impact the success of stem cell transplantation. Considering all the combinations of donor/recipient sex interaction could improve clinical efficiency.
The researchers call for further study to see how this finding translates to humans, as it could have implications for cancer development and how males and females respond to treatment.
Last year, Medical News Today reported that different immune cells are responsible for pain in male and female mice.