Medical Discovery News 
By Drs. David Niesel and Norbert Herzog 

 Despite centuries of women being celebrated for siring sons, or scorned for failing to produce an heir, it is actually men who determine a baby’s gender. Women give each of their offspring an X chromosome, but the male can give an X or a Y chromosome to create a female (XX) or male (XY), respectively. But how much of the Y chromosome is required to make a male? It turns out only two genes are needed to create a male mouse, a species that determines gender the same as humans.

Humans have 23 pairs of chromosomes, one of which is the sex chromosome. Chromosomes contain lots and lots of genes, all which carry instructions that tell different parts of the body what to do. In males, the Y chromosome carries a gene called SRY that encodes the Sex-determining region Y (also abbreviated SRY) protein. This protein, as its name suggests, will decide the sex of future offspring. Consequently, this one single gene, SRY, is all that’s required to produce an anatomically male mouse. However, these male mice are infertile because they lack some of the genes involved in sperm production.

That’s where another gene called Eif2s3y comes in. With this second gene, male mice can at least generate sperm cell precursors known as round spermatids, but not mature sperm. To fully develop sperm, the mice need both copies of this gene. One is toward the end of the Y chromosome and the other version is on the X chromosome.

So with only two genes from the Y chromosome, male mice are able to produce immature sperm. Scientists used an assisted in vitro fertilization technique to treat male infertility by injecting the round spermatids directly into the eggs of female mice. The round spermatids fertilized the eggs nine percent of the time. In comparison, sperm from natural-born male mice fertilized eggs 26 percent of the time. The offspring born from these efforts developed into normal, healthy, fertile adult mice.

Even though only two genes from the Y chromosome are required to produce fertile adult mice, the Y chromosome is still important. More genes are required to produce fully mature, motile sperm capable of fertilizing an egg without intervention. The Eif2s3y gene may play a role in some forms of male infertility in humans. With this new data, therapies could be invented to encourage the development of functional sperm that could reproduce through in vitro methods. Injecting round spermatid into eggs is not currently an option for humans due to technical and safety issues, but this technique is likely to get better with additional research.

The genetic information contained in the Y chromosome plays important roles in reproduction by controlling the development of sperm and normal fertilization and will continue to do so, negating suggestions that it is being eliminated by evolution or rendered useless by in vitro fertilization. For now at least, men remain indispensable.
