Genetic causes of male infertility / 中华男科学杂志

ABSTRACT

The causes of spermatogenetic failure found in most cases of non-ohstmctive azoospermia or severe oligospermia remain largely unclear. It is estimated that in about 30% of the cases, male infertility is due to genetic causes, including chromosomal abnormalities, Y chromosome microdeletions, gene mutations, etc. Klinefelter's syndrome and microdeletions in the Y chromosome long arm (Yq) represent the most frequent molecular genetic cause of severe infertility. Gene mutations involved in male infertility include the cystic fibrosis transmembrane conductance regulator (CFTR) gene, androgen receptor (AR) gene, insulin-like factor 3 (INSL3) gene and leucine-rich repeat-containing G-protein coupled receptor 8 (LGR8) gene. CFTR mutations cause cystic fibrosis, absence of vas deferens and non-obstructive azoospermia. The AR gene mutations are responsible for the androgen insensitivity syndrome and spermatogenetic damage. And INSL3 and LGR8 gene mutations have been associated with abnormalities in testis descent and cryptorchidism. Meta-analyses have revealed a significant association between the polymorphism and male infertility only for partial AZFc deletion, CAG repeat length in the AR gene and methylenetetrahydrofolate reductase (MTHFR) gene. This paper mainly reviews the genetic causes of male infertility and the genetic polymorphisms possibly associated with male infertility.