Is a genetic defect in Fkbp6 a common cause of azoospermia in humans?

FK506-binding protein 6 (Fkbp6) is a member of a gene family containing a prolyl isomerase/FK506-binding domain and tetratricopeptide protein-protein interaction domains. Recently, the targeted inactivation of Fkbp6 in mice has been observed to result in aspermic males and the absence of normal pachytene spermatocytes. The loss of Fkbp6 results in abnormal pairing and a misalignment of the homologous chromosomes, and in non-homologous partner switches and autosynapsis of the X chromosome cores in meiotic spermatocytes. In this study, we analyzed whether human FKBP6 gene defects might be associated with human azoospermia. We performed a mutation analysis in all the coding regions of the human FKBP6 gene in 19 patients with azoospermia resulting from meiotic arrest. The expression of the human FKBP6 gene was specific to the testis, and a novel polymorphism site, 245C --> G (Y60X) could be found in exon 3. Our findings suggest that the human FKBP6 gene might be imprinted in the testis based on an analysis using two polymorphism sites.

Nuclear dynamics of parthenogenesis of human oocytes: effect of oocyte aging in vitro.

We investigated in detail the nuclear kinetics of oocyte activation of aged human oocytes following combined activation treatment with calcium ionophore and puromycin. Two types of oocytes were used: (a) 1-day-old oocytes after 20-24 h retrieval, and (b) 2-day-old oocytes after 44-50 h retrieval. A total of 185 unfertilized aged oocytes, 91 1-day-old and 94 2-day-old oocytes, were fixed at 1, 2, 4, 6 and 8 h after activation treatment and then metaphase II (MII), anaphase or telophase II (A/T II) or pronuclear stage were recorded. We demonstrated that a combined calcium ionophore and puromycin treatment induced a high activation rate in both 1-day-old (95.6%) and 2-day-old oocytes (95.2%). Our results also demonstrated that the nuclear progression was faster in 2-day-old oocytes than in 1-day-old oocytes, although nuclear progression in parthenogenetically activated human oocytes requires the longer time periods compared with ICSI fertilization. It is concluded that combined treatment of the calcium ionophore and puromycin allows a high rate of parthenogenetic activation and the nuclear kinetics of parthenogenetically activated human oocytes appears to be more rapid in in vitro aging oocytes.