Fitting Into Your Genes

Posted on by Paul Turek, MD

“Why Me? I take great care of myself.”
I often hear this common question from men with low or no sperm counts who are unable to conceive. In fact, they usually are taking great care of themselves. The fact is, many cases of male infertility are actually genetic and have more to do with the cards that they were dealt.
“But my brothers, sisters and cousins all have kids…!”
Here where is gets a little complicated, as not all genetic traits are handed down the same way. There’s autosomal recessive and dominant, sex-linked, sex-limited, Mendelian and non-Mendelian, and even polygenetic and epigenetic. The thinking implied by this comment is Mendelian, which one of only a few ways to pass genetic traits along. The way infertility occurs is not necessary like that of heart disease or high blood pressure.

Genes and You

What is that saying? “Clothes make the man.” A more modern (and accurate) way of saying this is that “Genes make the man.” And with male infertility, it is becoming quite clear that genes matter a whole lot.
For 50 years, as men were evaluated for infertility, clinicians would simply use the term “unexplained” or “idiopathic” to describe much of what they saw. As the Y chromosome was found to have important genes for “maleness”, interest turned toward this chromosomal location to explain infertility as well. Then, in the mid-1990s, a colleague of mine discovered an area on the Y chromosome that could explain why a chunk of men had low or no sperm counts. Now, it is clear that the Y chromosome is central to normal male fertility.
It is thought that between 500 and 1000 genes are involved with sperm production. This is a reasonably big lot of the estimated 25,000 genes that exist in the human genome. However, currently, fewer than 50 genes have been definitively linked to male infertility. Some of these are on the Y chromosome, but many are not, making the story even more complex than originally thought.

My Answer to “Why Me?”

My long answer to the question “Why me?” revolves around the concepts that 1) there are two different genetic evolutions in the body, and 2) that your genes may be new to you and may not be handed down like clothes. It goes something like this:

  • Eggs and sperm (also called “gametes”) are responsible for the vast bulk of human evolution. They have a very long term view of where our species is going.
  • As a consequence, genes in our gametes constantly mutate and change, as change is the engine of evolution. Genetic change in our gametes is expected, nay necessary, for our proper evolution. They mutate rapidly and frequently.
  • On the contrary, genes in the rest of the body exist to support the work of the gametes, for the good of the species. So, the rate genetic mutations in this system is much lower. As the rocket (body) for the payload (gametes) the body must run fast, hard and true.
  • Given this setup, with evolutionary pressure high in gametes, new mutations occur far more commonly there than in the rest of the body.
  • Another way of looking at this is that if every mutation that occurred in our gametes was made manifest in our bodies, we would look entirely different from one generation to the next. Luckily, this isn’t the case, because the quality control “filter” is so good.
  • But it does explain why there is a lot more genetic change affecting infertility than one might expect.

Maybe it’s true that clothes make the man, but with male fertility it is also true that the clothes were newly purchased and not hand-me-downs.