Genetics and stem cells

Study 'casts doubt' on the need for a Y chromosome

“Y chromosome: why men contribute so little,” is the headline on BBC News, reporting that scientists may be able to ‘do away’ with the Y chromosome completely.

The Y chromosome is what makes men, well, men. Following conception male and female embryos start out the same, with very early stage sexual organs that have the potential to develop into either sex. At around the eighth week of pregnancy, the Y chromosome ‘kicks in’ triggering the development of male sexual organs.

The study being reported on involved mice genetically engineered to lack the entire Y chromosome (XO – where the O stands for missing, rather than XY mice – normal male mice), which would cause the mice to become infertile.

The XO mice were made “male” by the further addition of two genes: one that would cause the development of testes and one that would cause the testes to produce sperm. However, the development of both testes and sperm was stunted to an extent.

Never the less, these sperm cells were able to successfully fertilise a mouse egg cell in the laboratory using IVF techniques.

This is interesting research furthering our understanding of reproductive biology.

However, humans are not the same as mice, and as the researchers rightly conclude: “Our findings are relevant, but not directly translatable, to human males”.

Where did the story come from?

The study was carried out by researchers from University of Hawaii and was published in the peer-reviewed scientific journal Science Express. No sources of funding are reported.

The article on the BBC News website makes for interesting reading, and as Dr Chris Tyler-Smith, from the Wellcome Trust Sanger Institute, is quoted as saying: “This is a great step forward in understanding basic biology”.

However, the study has very limited direct relevance to humans, and does not suggest that ‘men contribute little’ or that the Y chromosome – ‘the symbol of maleness’ could be obliterated. 

What kind of research was this?

The researchers say that the Y chromosome is known to code for a number of genes, and that much work has been done to see which genes are needed to maintain normal sperm function.

They add that with assisted reproductive techniques it could now be possible to get past the problems of immature or immotile sperm which may be caused by gene defects.

This laboratory research in mice aimed to further understanding of which genes normally coded for on the Y chromosome are important for the production of sperm. To do this they used mice genetically engineered to lack a Y chromosome, and looked at which genes they needed to ‘add back in’ in order for the mouse to develop sperm that were able to fertilise egg cells and produce live offspring.

What did the research involve?

Male animals would normally have an XY sex chromosome pair (and females XX). The current study used mice who were genetically engineered to be XO, meaning that they had one X chromosome but complete absence of a Y chromosome.

They were made ‘male’ by the addition of the Syr gene which drives the development of testes (making the mice XOSyr).

Early stage sperm cells develop in XOSyr mice; however, other genes on the Y chromosome are required for further sperm development.

The researchers identified the gene Eif2s3y as being a gene that would restore normal sperm cell proliferation.

They therefore added the Eif2s3y gene to the XOSry mice, which enabled them to produce sperm.

The researchers then investigated whether the sperm cells were able to fertilise an egg cell using assisted reproduction techniques.

What were the basic results?

The mice lacking the Y chromosome (but with the Sry and Eif2s3y genes added) had smaller testes than normal XY mice. Examination of the testes demonstrated they were producing sperm, but in low numbers, and the sperm did not go through the full stages of normal development. There were also some abnormalities to the structure of the seminiferous tubules, were the sperm are made and transported within the testes.

The researchers then needed to test the function of the sperm-like cells the mice were producing. They could obtain samples containing sperm-like cells from all of the XO mice, but only in low numbers, and many of the sperm cells hadn’t finished developing. They had abnormal shape with a larger size than normal sperm, and had a large nucleus, and a rough rather than a smooth-looking appearance.

The researchers injected these sperm cells into mouse egg cells using the technique of intracytoplasmic sperm injection (ICSI). ICSI is an assisted reproduction technique already used in humans. As only a single sperm has to be injected into the egg, it means fertilisation is possible when few sperm are available from the male partner, for example if they have a very low sperm count or there are other problems with the sperm such as having poor shape or not being able to swim very well. The egg is fertilised in the laboratory and then transferred back into the mother’s uterus. 

However, the specific technique used in this study was called ‘round spermatid injection’, as it involved injection of precursors of mature sperm cells (immature sperm cells). This technique is considered ‘experimental’ in humans as there are still concerns about the safety of the technique and because of technical difficulties.

The sperm injected from the XO mice could successfully fertilise egg cells. Three out of four males were able to produce sperm that successfully fertilised an egg, which when transferred back into the mother’s body, resulted in live offspring. The offspring were healthy, and those that were later bred, were shown to be fertile.

However, the success of ICSI when sperm from XO mice was used was lower than when sperm from normal XY mice were used: a 9% success rate compared with 26% when normal mice were used.

How did the researchers interpret the results?

The researchers conclude that with the use of assisted reproduction, live offspring could be obtained from mice who lacked the entire Y chromosome and had only two genes added to allow testes development (the Sry gene) and sperm production (the Eif2s3y gene). They say their “findings are relevant, but not directly translatable, to human males”.


This is interesting research furthering our understanding of reproductive biology. It demonstrates that even with complete lack of the Y chromosome the addition of two genes, Sry and Eif2s3y, enabled the mice to develop testes and then to produce sperm – albeit in low numbers and with structural abnormalities.

It is very unlikely that these mice would have been able to father any offspring if allowed to mate naturally. However, IVF techniques demonstrated that the sperm cells they produced were able to fertilise an egg, and apparently go on to produce live and healthy, fertile offspring.

However, mice are not the same as men, and in men the genes involved in the production of healthy sperm are not identical to those studied here in mice.

The main conclusion of the researchers says it all: “Our findings are relevant, but not directly translatable, to human males”.

It seems, at least for the time being, that the Y chromosome is here to stay.

NHS Attribution