Microdeletions within the azoospermia factor (AZF) region of the Y chromosome and the expansion of the CAG trinucleotides in the androgen receptor (AR) gene are among the susceptible causes of male infertility in different ethnic groups.
The animal model for male infertility with high aromatase activity showed reduced numbers of AR-immunoreactive testicular peritubular cells, suggesting that altered androgen and/or oestrogen levels could influence AR-mediated responses in peritubular cells.
The androgen receptor (AR) plays a crucial role in normal physiology, development and metabolism as well as in the aetiology and treatment of diverse pathologies such as androgen insensitivity syndromes (AIS), male infertility and prostate cancer (PCa).
Increased AR-CAG repeat length was also associated with azoospermia.This meta-analysis supports that increased androgen receptor CAG length is capable of causing male infertility susceptibility.
Different mutations in AIS generally cause variable phenotypes that range from a complete hormone resistance to a mild form usually associated with male infertility.
Our results validate the concept that long stretches of CAG repeat may be associated with lower AR function with derangement of sperm production, and this may contribute to male infertility in Egyptian men.
Transcriptional profiling of luteinizing hormone receptor-deficient mice before and after testosterone treatment provides insight into the hormonal control of postnatal testicular development and Leydig cell differentiation.
Our objective was to evaluate a possible association between male infertility and mutations in the androgen receptor gene based on the presence or absence of exons 1 and 4 of this gene.
The androgen receptor (AR) is a protein encoded by the AR gene, which when mutated may affect spermatogenesis, the process in which spermatozoa are produced; thus, AR mutations could lead to male infertility.
It is generally accepted that defects in the AR gene prevent the normal development of both internal and external genital structures in 46,XY individuals, causing a variety of phenotypes ranging from male infertility to completely normal female external genitalia.
For example, among endocrine-related-diseases, the PolyGln size has been proposed to be associated to prostate cancer susceptibility, hirsutism, male infertility, cryptorchidism (in conjunction with polyglycine stretches polymorphism), etc.; the molecular mechanisms of these alterations are thought to involve a modulation of AR transcriptional competence, which inversely correlates with the PolyGln length.
Thus in a very near future, for a comprehensive male infertility panel, it will be essential to include additional genetic tests, such as CFTR gene mutations, sperm mitochondrial DNA mutations, and androgen receptor gene mutations, besides the conventional chromosomal analyses, Y chromosome microdeletion detection, and sperm-FISH analyses.
To this aim, we selected four AR missense mutations associated with isolated male infertility (L547F and two novel mutations A474V and S650G) or partial AIS (Y571H).
In conclusion, our results implicated the AR-HAP4 gene haplotype in increased risk for male infertility, while no association was found between AR CAG/GGN microsatellites and impaired spermatogenesis.
Thus in a very near future, for a comprehensive male infertility panel, it will be essential to include additional genetic tests, such as CFTR gene mutations, sperm mitochondrial DNA mutations, and androgen receptor gene mutations, besides the conventional chromosomal analyses, Y chromosome microdeletion detection, and sperm-FISH analyses.
Our goals were to summarize published data on associations between AR CAG and GGC repeat lengths and male infertility and investigate sources of variation between study results.
While the correlation between the CAG repeat length of the androgen receptor (AR) gene and idiopathic male infertility is still unclear, ethnic background of the population studied may play an important role in this association.