Role of nuclear and mitochondrial genes in human male infertility: a review

Infertility affects very high percentage (15%) of couples and nearly 50% of these are accountable to the male partners. Reproduction encompassed two important biological processes are successful gametogenesis and fertility. Mainly, male infertility is influenced by the sperm quantity and quality. Male infertility is genetically heterogeneous. Numerical and structural chromosomal abnormalities are associated with male infertility. Genetic studies on male infertility suggest that mutations in some Y chromosomal genes lead to male infertility. The major spermatogenic candidate genes are present in the Azoospermia factor loci (AZFa, AZFb and AZFc) of Y chromosome that largely control the successful spermatogenesis. Deletions or mutations in these genes results in abnormal spermatogenesis or abnormal semen profile affecting the fertility. The gr/gr deletion, a partial 1.6 Mb deletions in AZFc region of Y chromosome, has also been described specifically in infertile men with varying degrees of spermatogenic failure. A number of X-chromosomal and autosomal genes mutations have also been implicated for male infertility. It is suggested that impaired sperm chromatin integrity or sperm nuclear DNA damage has been associated with male infertility. It is not only genetic but genomic imprinting, an epigenetic phenomena, play a crucial role in male infertility. PLOG (DNA polymerase gamma) gene mapped to the long arm of chromosome 15 (15q25) includes CAG repeats and its mutations may affect the adenosine triphosphate production and fertility. Studies on mitochondrial genes revealed that mitochondrial genes are involved in normal growth, development and differentiation of sperms, and are also responsible for flagellar movement of sperms after ejaculation. Mutations in these mitochondrial genes result in abnormal semen parameters and impaired sperm flagellar movements which result in problem in fertilization and ultimately in infertility.