Genetic Causes of Male Infertility

GeneticsThe human genome is the complete set of instructions for building a human.

It is made up of 23 pair of chromosomes which each have somewhere between 500 – 5,000 individual genes, each of which are responsible for a particular trait – hair color, eye color, etc. 22 of the chromosome pairs are the same in men and women, but the last set is the sex chromosome. Women have 2 X chromosomes (XX), while Men have an X and a Y (XY).
When a baby is conceived the baby’s DNA comes from both the father and the mother. The egg contains a single set of 23 chromosomes and the sperm contains the other 23. When the sperm fertilizes the egg, the two sets of chromosomes combine to form a full set of DNA for the new little person. Interestingly, the gender of the baby is determined by the man. Sperm can carry either an X or a Y chromosome which will determine whether the baby will be a boy or a girl.

Genetic disorders can be divided into a few different categories. Numerical chromosomal abnormalities occur when a person receives an extra chromosome, which can cause various disorders such as Down’s or Turner’s syndrome. Another thing that can happen is pieces of a gene can get deleted during duplication. Most of the time, large deletions cause severe enough disorders that don’t enable an embryo to develop. However, some very small deletions, known as micro-deletions can lead to a variety of congenital defects including infertility. Microdeletions in the Y chromosome have a profound impact on sperm production and is a fairly common cause of infertility in men. Finally, mutations or trans-locations are disorders where parts of a gene form abnormally or get mixed up with other genes causing it to malfunction. This can cause disorders such as cystic fibrosis or sickle cell anemia. Sometimes these mutations can impact fertility.


Aneuploidy or Numerical Abnormalities

As mentioned above, the most well-known of the numeric abnormalities is trisomy 21 or Down’s Syndrome. This occurs when someone receives an extra copy of the 21st chromosome and happens in about 1 in every 700 births. It is also fairly common to have extra copies of either the X or the Y chromosome. Some women may have a an extra X resulting in a condition known as triple X. Men can receive either an extra X or an extra Y chromosome, resulting in XXY or XYY. Rarely, babies are born that are genetically female with two X chromosomes but present as males.

Klinefelter Syndrome

Topic: Klinefelter Syndrome

The most common genetic cause of male infertility is a condition known as Klinefelter Syndrome. About 1 in every 500 boys are born with an extra X chromosome in their genetic makeup – “XXY.” This condition is known as Klinefelter Syndrome, and it has been shown to drastically reduce the man’s fertility.



Topic: Y Chromosome Microdeletion

Microdeletions make up another large portion of the genetic causes of male infertility. Most of the time deletions occur on the Y chromosome.

Y Chromosome Microdeletions

The Y chromosome is by far the smallest chromosome and is primarily responsible for the creation of sperm and the development of tissue in the testicle. Because it is only passed from man to man via sperm, and sperm are continually being made by the body, it has a higher risk of mutating from one generation to the next when compared to the other genes. When a man has Y microdeletions, it is kind of like having a few bad sectors on a hard drive, it really doesn’t affect anything EXCEPT trying to make sperm. It’s estimated that somewhere around 10% of azoospermic men have these micro-deletions but the number could be bigger as it has been traditionally difficult and expensive to diagnose.

Prader-Willi Syndrome

Another genetic disorder caused by microdeletions is Prader-Willi Syndrome. This syndrome is incredibly rare occurring once in every 25,000 births. It is caused by microdeletions on the 15th chromosome and is commonly diagnosed via genetic testing at birth. Like autism, Prader-Willi is a spectral disorder with a range of symptoms from mild to severe. The most common symptoms include hypgonadism, infertility, small hands and feet, and obesity stemming from an uncontrollable appetite.

Genetic Mutations

Scientists estimate that there are around 2,300 genes involved in male reproduction. Each gene has several possible mutations, making it nearly impossible to isolate all genetic causes of infertility. The rise in genetic sequencing and other genetic testing techniques has dramatically increased our understanding of how genes impact our health and fertility. Here are some of the more common genetic mutations that can impact fertility.

Cystic Fibrosis

Cystic Fibrosis is one of the most well known genetic mutation disorders. It occurs when there is a mutation in the CFTR gene (located on the 7th chromosome). This gene is responsible for helping your body regulate use of salt and over 1,200 mutations of the gene have been identified by scientists. Full blown CF occurs when an individual has two copies of a mutated gene, which happens about once in every 2,500 births. Thanks to modern medicine, CF patients are living longer, healthier lives and many are able to start families of their own. However, a hidden side-effect of CF is that it can often cause a natural vasectomy by preventing the formation of the vas deferens. Skilled urologists specialized in fertility are able to help men with CF become fathers.
A lesser known fact about CF is 1 in 25 people carry one copy of the mutated gene. Some mutations specifically impact the formation of the vas deferens, so even men who don’t have full blown CF may be genetic carriers with unexplained obstructive azoospermia. A skilled urologist should be able to detect the absence of the vas deferens during a physical evaluation and recommend genetic testing if a CF mutation is suspected.

Other genes linked to male fertility

Mutations in key genes involved with fetal development can prevent the testicles from descending. Other mutations can cause abnormal development of the ducts that connect the testicles to the body. Since sperm production is regulated by hormones, genetic problems with the endocrine system may also create conditions that are unfavorable for or preclude sperm production. Some of the known syndromes stemming from genetic mutations that affect male fertility include: Noonan Syndrome, Androgen Insensitivity Syndrome, Kallman Syndrome, Myotonic Dystrophy, and Kartagener’s Syndrome.

Sara SDx

Sara SDx

Editor of Don't Cook your Balls, Co-Founder of, Health Coach and Men's Health Advocate. Passionate about sperm, men's health and helping people build their families.
Sara SDx

Author: Sara SDx

Editor of Don't Cook your Balls, Co-Founder of, Health Coach and Men's Health Advocate. Passionate about sperm, men's health and helping people build their families.

7 thoughts on “Genetic Causes of Male Infertility”

  1. […] The human genome is a complete set of instructions for human beings. It is made up of 23 pairs of chromosomes and each pair has between 500 – 5,000 genes. Genes are responsible for particular traits such as eye color, hair color, etc. All pairs of chromosomes are the same in a man and a woman except one, the sex chromosome. Men have a Y and X chromosomes (XY) while women have two X chromosomes (XX). Some changes to genes and chromosomes cause abnormal production of sperm or blockage to flow of sperm that leads to male infertility. Chromosomal conditions are the most common genetic causes of male infertility. Chromosomal conditions that affect sperm production include Y chromosome deletions, Klinefelter’s syndrome, prader-willi syndrome, and other genetic conditions such as Down syndrome. Infertility due to a gene mutation is less common. Mutations in the cystic fibrosis gene result in the congenital absence of the vas deferens. This causes blockage to flow of sperm. Other genes linked to fertility are those that prevent the testicles from descending. It is likely that other genetic conditions will be found in future that will allow scientist to explain other causes of male infertility that currently have no known cause. References […]

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