Silencing of unpaired meiotic chromosomes and altered recombination patterns in an azoospermic carrier of a t(8;13) reciprocal translocation

BACKGROUND: Male carriers of structural chromosomal abnormalities provide a useful model for studying the effects of impaired synapsis on human meioses and male fertility. METHODS: We used immunofluorescent techniques to examine recombination (MLH1), synapsis (SYCP3/SYCP1) and transcriptional inactivation (BRCA1/,gamma H2AX/RNA polymerase II) of meiotic chromosomes in an azoospermic carrier of a t(8;13) reciprocal translocation. Two biopsies were performed I year apart and on different testes. RESULTS: Global recombination rates differed between the two biopsies. Although global recombination rates were not altered when compared with control men, recombination frequencies were reduced specifically on the rearranged chromosomes. Asynapsed quadrivalents were observed in 90% and 87% of pachytene nuclei from the first and second biopsies, respectively, and were frequently associated with the sex chromosomes. BRCA1 and gamma H2AX, two proteins implicated in meiotic sex chromosome inactivation, localized along asynapsed regions regardless of whether or not they were associated with the sex chromosomes. Immunostaining for RNA polymerase II provided further evidence that unsynapsed regions are silenced during human meiosis. CONCLUSIONS: The fidelity of synapsis is a critical factor in determining the outcome of gametogenesis in humans, as the transcriptional inactivation of asynapsed regions may silence meiotic genes, leading to meiotic arrest and infertility.