INVESTIGATIONS ON THE MOLECULAR BASES OF GENETIC ASTHENOZOOSPERMIA

We propose to study the role of flagellar proteins/genes defects in infertile men with immotile spermatozoa (asthenozoospermia). We selected those genes which are responsible of Primary Ciliary Dyskinesia (PCD), an hereditary disorder characterized by recurrent pulmonary and upper respiratory tract infections (rhinitis, sinusitis and bronchitis). It is due to immotility of cilia covering the respiratory epithelium. Since the ultrastructure of the cilia is almost identical to the ultrastructure of the flagellum, these patients are often asthenozoospermic. Since the PCD phenotype is very heterogeneus, even in the same family, it will be possible that in vitro fertilization, seeked because of immotile sperm, might result in the trasmission of mutated alleles leading to PCD or male infertility. It may be possible, and our preliminary data confirm this hypothesis, that different mutations in the dyneins genes lead to different phenotypes, eg.: men with non syndromic asthenozoospermia and no respiratory problems. It is very important to begin to discriminate between environmental and genetic asthenozoospermia, since it is possible to overcome the problem with ICSI (Intra-Citoplasmatic Sperm Injection) and it is obvious that responsible reproductive choices may be done only if patients know if they are or not carriers of a genetic condition. This study will shed some light on the role of dyneins in non syndromic asthenozoospermia and it will add knowledge on the mechanisms leading to movement of cilia and flagella. The role of dyneins abnormalities in male infertility with absent or mild respiratory disorder has never been investigated.