Study On Association Between Partial Deletions Of The AZFc Region And Y Chromosome Haplogroups And Male Spermatogenic Failure

The rate of male infertility is about 5-8%, among those patients, idiopathic male infertility account for 11.2%. The major form of idiopathic male infertility is spermatogenesis impairment. The chief pathogeny is chromosomal abnormality which can only account for 2-5%. Thus, there are still more causes associated with genetic factors leading to idiopathic male infertility remain to be deciphered.Firstly , our investigation screen the deletion of 11 STSs sites in the AZFc and AZFb reigons in normal fertile and spermatogenic impairment groups. Those specimens are examined the deletions of 10 STSs sites in the AZFb reigon which are likely to relate to massive deletions to determine the recombinant deletion mechanism. PCR am plication of deletion junctions are used to localize the breakpoints precisely and demonstrate occurrence of AZFb+c massive deletion.Next we have screened SNV (single nucleotide variant) sites in DAZ, CDY1 and BPY2 to detect those gene family copy deletions in men which lack sY1191and sY1291 and to conclude the precisely homologous recombination mechanism among these amplicons. To investigate the correlation of between AZFc region partial haplotype deletions and male spermatogenesis failure, we have analysed the distributing frequency by SPSS11.0 statistical software.Finally, Y chromosome haplogroups were typed in unselected general men , azoospermia and oligozoospermic men groups. We expect to obtain the distributing datum of Y chromosome haplogroups from Sichuan Province Han people and study the association of Y chromosome haplogroups and male spermatogenesis failure. The main results are as follows:1. 14 kinds of AZFc region deletion haplotypes are observed, among which the mechanisms of 10 kinds deletion haplotypes could be inferred, but the else 4 kinds deletion haplotypes could not be inferred by using homologic recombination of existing amplicons of AZFc region and among which b2/b4 recombination deletion is the genetic pathogeny and only found in oligospermic and azoospermic patients. The partial deletion haplotypes of sY1291/DAZ1/DAZ2 are the higher risk factors of male spermatogenesis impairment. The difference of frequency distribution of sY1291/DAZ3/DAZ4 partial deletion haplotype has no statistical significance. The frequency of deletion haplotype sY1191/DAZ3/DAZ4 is higher in normal group than spermatogenesis impairment group.2. There are 9 samples with massive deletions of AZFb+c region in azoospermia among which 2 samples have the P5/proximal-P1 deletion, 2 samples have the P5/distal-P1 deletion, 2 samples have the P4/distal—P1 deletion and 2 samples have the novel deletion which have not been reported in the literature so far. Further, the deletion junctions of sample A01590, A01224, A01756 and A01184 were amplified with primers of 10827/12088, 10824/10916 and 11086/11087 respectively. These primer sequences and PCR conditions were as described in the literature (Repping et al., 2002). they were similar to those identified before. Deletion sites of the other samples precisely locating should been ulteriorly studied.3. 14 haplogroups have been observed, in which haplogroups H2 and H4 are identified for the first time in the population, and haplogroups H14 and N~* are reported firstly in Chinese. There was significant frequency difference of Y haplogroups between Sichuan Han and Southern Han.4. There is no significant difference of spermatogenesis ability in the Y haplogroups, but those susceptibilities of spermatogenesis impairment have statistical significance.