Male infertility refers to a male's inability to cause pregnancy in a fertile female. In humans it accounts for 40–50% of infertility. It affects approximately 7% of all men. Male infertility is commonly due to deficiencies in the semen, and semen quality is used as a surrogate measure of male fecundity. Chromosomal anomalies and genetic mutations account for nearly 10–15% of all male infertility cases. Klinefelter syndrome One of the most commonly known causes of infertility is Klinefelter syndrome, affecting 1 out of 500–1000 newborn males Klinefelter syndrome is a chromosomal defect that occurs during gamete formation due to a non-disjunction error during cell division. Resulting in males having smaller testes, reducing the amount of testosterone and sperm production. Males with this syndrome carry an extra X chromosome (XXY), meaning they have 47 chromosomes compared to the normal 46 in each cell. This extra chromosome directly affects sexual development before birth and during puberty (links to learning disabilities and speech development have also been shown to be affected). There are varieties in Klinefelter syndrome, where some cases may have the extra X chromosome in some cells but not others, referred to as mosaic Klinefelter syndrome, or where individuals have the extra X chromosome in all cells. The reduction of testosterone in the male body normally results in an overall decrease in the production of viable sperm for these individuals thereby forcing them to turn to fertility treatments to father children. Y chromosome deletions Y chromosomal infertility is a direct cause of male infertility due to its effects on sperm production, occurring in 1 out of every 2000 males. Usually affected men show no sign of symptoms other than at times can exhibit smaller teste size. Men with this condition can exhibit azoospermia (no sperm production), oligozoospermia (small number of sperm production), or they will produce abnormally shaped sperm (teratozoospermia). This case of infertility occurs during the development of gametes in the male, where a normal healthy male will produce both X and a Y chromosome, affected males have genetic deletions in the Y chromosome. These deletions affect protein production that is vital for spermatogenesis. Studies have shown that this is an inherited trait; if a male is fathered by a man who also exhibited y chromosome deletions then this trait will be passed down. These individuals are thereby “Y-linked”, although daughters are not affected due to the lack of the Y chromosome.

There is increasing evidence that the harmful products of tobacco smoking may damage the testicles  and kill sperm, but their effect on male fertility is not clear. Some governments require manufacturers to put warnings on packets. Smoking tobacco increases intake of cadmium, because the tobacco plant absorbs the metal. Cadmium, being chemically similar to zinc, may replace zinc in the DNA polymerase, which plays a critical role in sperm production. Zinc replaced by cadmium in DNA polymerase can be particularly damaging to the testes.

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