Endocrine Abstracts

Male infertility is a common disorder and a growing health problem. A large proportion of unexplained cases have been summarily categorised as idiopathic infertility. The majority of idiopathic cases, especially those with severely impaired spermatogenesis incl. azoospermia, are presumably caused by genetic defects. Genetics of male infertility has been a largely unexplored area, until quite recently, when new molecular tools unabled discovery of a growing number of genes involved in spermatogenesis and gamete maturation, e.g. genes mapped to the AZF region of the Y-chromosome and some genes on the X-chromosome. In addition, several pathways related to hormonal regulation of reproductive function contain polymorphic genes, which may affect the function of a given gene in a discrete manner, such as the CAG and GGN repeats on androgen receptor, or polymorphisms in CYP, INSL3 genes. Finally, polymorphisms of genes seemingly unrelated to the reproductive function, have been associated with male infertility, e.g. mitochondrial gene polymerase, POLG. A rush to analyse polymorphic genes in various populations, often with poorly characterised cases and controls, created a lot of confusion in the literature as to the real pathogenetical involvement of the studied genes in male infertility. There is a need for large and well-controlled studies, underpinned by basic functional studies of the investigated genes. A great care must be taken to use proper control groups, which must be selected with fertility, ethnicity, and age of the subjects in mind. A very important point is having in mind that environmental exposures and/or lifestyle factors frequently exert their influence primarily in genetically predisposed individuals. A good description of the reproductive parameters (outcomes), preferably with the analysis of the reproductive function on children, is also essential for the analysis of the consequences of studied polymorphism/ gene aberration, and for an early prognosis as to the future fertility problems.