Meiotic defects and decreased expression of genes located around the chromosomal breakpoint in the testis of a patient with a novel 46,X,t(Y;1)(p11.3;p31) translocation

Balanced translocations are known to be associated with infertility, spontaneous abortions and birth defects in mammals. Spermatocyte spreading and immunostaining were applied to detect meiotic prophase I progression, homologous chromosome pairing, synapsis and recombination in an azoospermic reciprocal translocation 46,X,t(Y;1)(p11.3;p31) carrier. Histological examination of testicular sections revealed a severely reduced number of germ cells with no spermatids or sperm in the carrier. A significant reduction in XY recombination was observed in the patient. The number of MLH1 foci on autosomes that are not involved in the translocation per cell was also significantly decreased in our patient as compared to the controls, which indicates an inter-chromosomal effect (ICE) of the translocation on recombination. An increase in leptotene (P<0.001) and zygotene (P<0.001) and a decrease in pachytene spermatocytes (P<0.001) were observed in the carrier when compared with the controls, indicating disturbed meiotic progression in the patient. Increased RAD51 foci during pachytene (P=0.02) in the spermatocytes of the patient were noted. A decreased expression of the genes (USP1, INSL5, LEPR and MSH4) critical for meiosis/spermatogenesis and located around the breakpoint region of chromosome 1 was observed in the 46,X,t(Y;1) carrier, which may further exacerbate the meiotic failure such as reduced recombination on autosomes and ultimately cause spermatogenesis arrest. In summary, we report a series of events that may have caused infertility in our 46,X,t(Y;1) carrier. To the best of our knowledge, this is the first report shedding light on how, possibly, a reciprocal translocation affects meiosis at the molecular level in azoospermia patients.