Abnormal Meiotic Recombination And Chromosome Behavior In Male Infertility Patients

Objective:To investigate the effects of two Y chromosome on the process of spermatogenesis and meiotic abnormalities including pairing,synapsis and recombination in spermatocytes of a XYY man, trying to find more cytogenetic mechanism for the infertility of XYY patients.Method:1. Immunofluorescence staining method and cell spreading technique were used to prepare synaptonemal complexes of spermatocytes from the patient. The lateral elements of the SC, recombination sites and centromeres were stained by antibodies against SCP3, MLH1 and CREST respectively.2. Anti-y-H2AX antibodies were used to mark chromosome synapsis and unsynapsed regions on meiotic chromosomes.3. FISH techniques were employed to identify the Y chromosome..4. spermatogenesis of the patient was observed under testicular tissue sections.Results:Testicular histological examination of the patient showed reduced germ cells with no mature spermatids or sperm. A total of 71 pachytene spermatocytes were analyzed for the pairing between homologous chromosomes. No abnormal pairing between homologous autosomes were found in all cells analyzed. For sex chromosomes,42 out of 71 (or 59.2%) cells showed pairing in whole Yp and partial Yq, while the pairing extended to the whole length of Ychromosomes in the remaining 29 (or 40.8%) cells. For two Y chromosomes, partial and complete synapsis was observed in 52 and 19 spermatocytes, respectively. In all the 65 spermatocytes with partial or complete YY synapsis, recombination between two the Y chromosomes was observed in 27 out of 65 cells (41.5%). Recombination frequency of autosomes in the 47, XYY patient was determined in 71 pachytene spermatocytes and compared to those in 437 spermatocytes from five controls. The mean number of MLH1 foci per cell in the patient was significantly lower than those in controls (44.9 ± 4.6, vs.48.1 ± 5.8; P< 0.001, Mann-Whitney test).Meanwhile, following increased leptotene(P< 0.001, chi-square test) and zygotene spermatocytes (P< 0.001,chi-square test) , decreased pachytene spermatocytes (P< 0.001, chi-square test) were observed in the patient.Conclusion(s):Presence of extra Y chromosome would resulted in abnormal sex chromosome pairing, synapsis and recombination, and prevented the meiotic sex chromosome inactivation, leading to spermatogenesis embarrassment, germ cell loss and azoospermia.