Genetic variation in SPAG16 regions encoding the WD40 repeats is not associated with reduced sperm motility and axonemal defects in a population of infertile males

In the present study, we analyzed DNA samples from 60 infertile male volunteers of Western European (Italian) origin, to search for novel SPAG16 gene mutations, and to determine whether increased prevalence of SPAG16 single nucleotide polymorphisms (SNPs) was associated with infertility phenotypes. Semen parameters were evaluated by light microscopy and sperm morphology was comprehensively analyzed by transmission electron microscopy (TEM).For gene analysis, sequences were generated covering exons encoding the conserved WD40 repeat region of the SPAG16 protein and the flanking splice junctions. No novel mutations were found, and the four SNPs in the assessed gene region were present at expected frequencies. The minor alleles were not associated with any assessed sperm parameter in the sample population.Analysis of the SPAG16 regions encoding the conserved WD repeats revealed no evidence for association of mutations or genetic variation with sperm motility and ultrastructural sperm characteristics in a cohort of Italian infertile males.Infertility impacts approximately 9% of couples globally, with reports ranging from 3.5% - 16.7% of couples [1], and it is estimated that male factor infertility plays a role in as many as 55% of cases [2]. There are multiple causes of male infertility, including congenital factors and environmental exposures [3-5], as well as gene mutations which cause defects in spermatogenesis and sperm flagellar dysfunction.The most studied mutations associated with abnormal sperm motility and male infertility cause the primary ciliary dyskinesias (PCD) [6,7]. Genes involved in the structure and function of the “9？+？2” axoneme, the principle scaffold and regulator of motile cilia and flagella, have been extensively studied and characterized in the biflagellate eukaryotic algae Chlamydomonas, wherein loss of axonemal components has been shown to cause immotility [8,9]. Most of the mutations identified to date that cause PCD in humans encode proteins