Cytogenetic And Molecular Analyses Of Human Male Infertility

Current study was designed to explain the cytogenetic and molecular bases of sporadic cases of male infertility. It has two major sections (1) Meiotic analyses of the patients carrying unusual Y chromosome micro-deletions,(2) Mutational analysis of AR gene in patient with complete androgen insensitivity syndrome.First part:Several factors have been associated with male infertility; Y chromosome micro-deletions are the most common cause of male infertility and strictly associated with azoospermia by disrupting meiosis. There is not much known about the exact mechanism of meiotic arrest caused by Y chromosome micro-deletions. Previous meiotic studies on patients carrying AZFb and AZFc deletions have shown fragmentation of synaptonemal complex and an excess of early-stage pachytene cells. Here, current study describes the meiotic analyses of three exceptional azoospermia cases carrying AZFb+c+d and AZFc+d microdeletion. The analyses of data revealed that patients with AZFc+d deletion have extended zygotene along with impaired recombination, pairing and synapsis of homologous chromosomes. AZFb+c+d have more severe impact on meiosis progression and recombination, meiosis was arrested at zygotene stage. Abnormal pachytene-like cells were also seen in all patients in addition to high frequency of fragmented and dotted SC.Therefore, it is concluded that transient zygotene stage can be prolonged due to the absence of AZFb+c+d, AZFc+d regions. The high level of asynapsis and loss of germ cells at the pachytene checkpoint indicate that the AZFb+c+d, AZFc+d regions are critical for meiotic recombination and while deletion of AZFb+c+d deletion showed more severe impact on meiosis than the AZFc+d deletion. Second part:Complete androgen insensitivity syndrome (CAIS) is the X-linked inherited disorder caused by mutations in the androgen receptor (AR) gene. Previously various studies have been conducted to analyze mutations of AR and associated phenotypes in Human. But there is not much literature available about the effect of AR mutations on testicular histopathology of the CAIS patients. In current study, Sanger sequencing of androgen receptor gene identified a missense mutation c.1715A>G (p.Y572C) in the46, XY female patient bearing testis in his/her inguinal. This study explains the effect of mutation on the testicular histology of patient, which revealed presence of Sertoli cell only in the somniferous tubules. No sign of spermatogenic onset was seen. This is first ever study which report sertoli cell only phenotype in the patient with complete androgen insensitivity syndrome caused by mutant androgen receptor (AR) gene. A large scale study on the effect of AR mutations on the testicular histopathology is needed for better explanation of this phenomenon.