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Y chromosome and male fertility

Normal human beings have 23 pairs of chromosomes. One pair of these are called the sex chromosomes. Women have two X chromosomes and men have one X chromosome and one Y chromosome. Most, if not all of the genes that are responsible for sperm production in men are found on the Y chromosome. Abnormalities involving the sex chromosomes can result in sperm production problems and infertility. For example, men who have an extra X chromosome (XXY) are often lacking in sperm and are infertile. Men who have portions of the Y chromosome are missing (deletions) or redundant (duplications) can also show sperm production problems and infertility.

Male fertility and Y chromosome microdeletions

Microdeletions occur when very small pieces of the Y chromosome are missing. These problems cannot be detected through a routine chromosome analysis (karyotype). Microdeletions of the Y chromosome have been found in:

  • 2% or men with normal fertility
  • 7% of infertile men
  • 16% in men with azoospermia (no sperm in their ejaculate) or severe oligozoospermia (less than 1 million sperm)

To identify these microdeletions, special testing must be performed using a technology known as the polymerase chain reaction.

All chromosomes, including the Y chromosome, are divided into a “short arm” and a “long arm”.  Most deletions causing azoospermia or oligozoospermia occur in regions of the long arm known as the azoospermia factor (AZF) regions.  The AZF regions are further divided into

  • AZFa (proximal)
  • AZFb (central)
  • AZFc (distal)

Y chromosome

It appears that these regions, and possibly other regions of the Y chromosome, contain multiple genes necessary for normal sperm production. The specific location of the deletion along the Y chromosome and its size influences its effect on spermatogenesis.

AZFc microdeletions

Men with microdeletions in the AZFc region have sperm production but they will commonly have very low sperm concentration while other men will not have any sperm visible in their ejaculate. However, areas of sperm production can still be found with a testicular biopsy. If testicular sperm are found, they can be used during IVF to fertilize eggs and produce pregnancies.

AZFa and AZFb microdeletion

Men who have deletions involving the entire A2Fb region will rarely, if ever, have sperm in the ejaculate and doctors will rarely be able to find sperm with a testicular biopsy. The same may be true for men having deletions involving the entire A2Fa region of the Y chromosome.

What is the impact of the father’s Y chromosome microdeletion on his children?

Since daughters do not inherit a Y chromosome from their fathers, they will not have any fertility or health problems themselves. The sons, however, will inherit the abnormality and, therefore, may also have the same type of fertility problems as their fathers. What about other health issues? Unfortunately, there haven’t been a lot of studies on the children born to men with these microdeletions.  A study from 2011 found that some men with Y chromosome microdeletions also had abnormalities of another part of the Y chromosome (the pseudoautosomal regions or PARs). Abnormalities in one of the genes in this region, called the SHOX gene,  has been associated with short stature, mental retardation, and arm and wrist deformities. More work needs to be done in this area

Which men should have microdeletion testing?

Men who have no sperm in their ejaculate which is not due to a known obstruction, should have Y chromosome microdeletion testing. In addition, men who have otherwise unexplained low sperm concentration (less than 1 million) should also be tested unless they have fathered children in the past without any fertility treatments.