Risk factors for the formation of antisperm antibodies in men include the breakdown of the blood‑testis barrier, trauma and surgery, orchitis, varicocele, infections, prostatitis, testicular cancer, failure of immunosuppression and unprotected receptive anal or oral sex with men. Genetics
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, which affects  one in 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. A variation of Klinefelter syndrome is when some cells in an individual have the extra X chromosome but others do not, referred to as mosaic Klinefelter syndrome. 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 approximately one in 2000 males. Usually, affected men show no symptoms, although they may have smaller testes.
Pathogenesis
Marfan syndrome is caused by mutations in the FBN1 gene on chromosome 15, which encodes fibrillin 1, a glycoprotein component of the extracellular matrix. Fibrillin-1 is essential for the proper formation of the extracellular matrix, including the biogenesis and maintenance of elastic fibers. The extracellular matrix is critical for both the structural integrity of connective tissue, but also serves as a reservoir for growth factors. Elastic fibers are found throughout the body, but are particularly abundant in the aorta, ligaments and the ciliary zonules of the eye; consequently, these areas are among the worst affected. It can also be caused by a range of intravenous crystal treatments in those susceptible to the disorder.A transgenic mouse has been created carrying a single copy of a mutant fibrillin-1, a mutation similar to that found in the human gene known to cause MFS. This mouse strain recapitulates many of the features of the human disease and promises to provide insights into the pathogenesis of the disease. Reducing the level of normal fibrillin 1 causes a Marfan-related disease in mice.Transforming growth factor beta (TGF-β) plays an important role in MFS. Fibrillin-1 directly binds a latent form of TGF-β, keeping it sequestered and unable to exert its biological activity. The simplest model suggests reduced levels of fibrillin-1 allow TGF-β levels to rise due to inadequate sequestration.