PL 38. Clinical implication of Y chromosome microdeletions

The rates of infertility in normal couples are approximately ten to fifteen percentages and male factor is responsible about 50% of all cases of infertility. Among causes of male infertility, 25 to 60 percentages were reported as idiopathic or unexplained etiology. For part of these patients, a genetic factor will be the underlying cause of the problems. Common causes comprise chromosomal aberrations, microdeletions of the AZF loci of the Y chromosome, mutations in the gene responsible for cystic fibrosis (CFTR) causing CBAVD and in genes involved in hypogonadotropic hypogonadism. In men with severe oligospermia or nonobstructive azoospermia (NOA), an assay to identify microdeletions must be carried out prior to any intervention. This chromosome is enriched with genes expressed exclusively or prevalently in the testis and their absence or reduction of their dosage is associated with spermatogenic impairment.

AZFa deletion is rare and associated with the most severe phenotype such as complete absence of spermatogenesis with SCO. In complete AZFb deletion, there are no mature spermatozoa associated with germ cell development arrest at the pachytene stage. AZFc deletion is the most frequently deleted regionand the most common known genetic cause of male infertility. Complete or partial AZFc deletion shows variable phenotype from hypospermatogenesis to Sertoli cell-only syndrome. AZFd deletion is associated with mild oligozoospermia or even normospermia. In this lecture, I will present what is currently known about clinically relevant Y chromosome structural variations in male fertility.