A Study On Cytogenetics And Molecular Genetics In Patients With Male Infertility

Objective: To study the relationship between male infertility and genetic factors, including abnormal chromosome structure and number diversity, Y chromosome AZF microdeletion and partial AZFc deletions.Methods: After karyotype was analyzed in peripheral blood cell culture in 482 patients with azoospermia, severe oligozoospermia, oligozoospermia, and 214 males with normal semen and birth history, AZF microdeletions were detected by multiplex PCR in 446 patients with normal karyotype and 214 normal males. Then, partial AZFc deletions were detected in 404 patients without AZF microdeletion and 214 normal males. Deletions of DAZ gene copies were analyzed in the specimens with gr / gr and b2/b3 partial AZFc deletions by PCR-RFLP.Results:1. The incidence of abnormalities in structure and number of chromosome was 7.47% (36/482) in all patients with spermatogenesis disorders, and 12.62% (26/206), 5.23% (8/153), 1.62% (2/123), in patients with azoospermia, severe oligozoospermia and oligozoospermia, respectively. No abnormality of chromosomal was found in 214 normal males .2. The incidence of AZF microdeletions was 9.42% (42/446) in patients without abnormalities in structure and number of chromosome, and 12.22%, 11.72%, 2.48%, in patients with azoospermia, severe oligozoospermia and oligozoospermia, respectively. There were statistically significant differences in AZF microdeletions rate among patients with azoospermia, severe oligozoospermia and oligozoospermia (P <0.05). 23 cases of AZFd + c microdeletion (54.76 %) were detected in 42 patients with AZF microdeletions. And no AZF microdeletion was found in 214 normal males.3. 62 cases of partial AZF deletions were found in 404 patients without AZF microdeletions. Among them, there were 26 cases of gr/gr deletion, and 35 cases of b2/b3 deletion, 1 case of b1/b3 deletion. While, 22 cases of partial AZF deletions were found in 214 normal males, which included 15 cases of gr/gr deletion, and 7 cases of b2/b3 deletion. There were statistically significant differences in the incidence of b2/b3 deletion between normal males and patients with azoospermia, severe oligozoospermia, oligozoospermia patients and all spermatogenesis disorders (P<0.05). While, no statistically significant difference was found in the incidence of gr/gr deletion.4. Four types of DAZ gene copies deletion were detected in patients with gr/gr and b2/b3 deletion, which were DAZ1/DAZ2, DAZ3/DAZ4, DAZ1/DAZ4, DAZ2/DAZ3. There were statistically significant differences in the incidence of DAZ3/DAZ4 deletion between the patients with spermatogenesis disorders and normal males (P <0.05).Conclusions: There were relatively higher frequencies of chromosomal abnormalities in azoospermia, severe oligozoospermia and oligozoospermia than normal males. The Klinefelter syndrome was still the most common abnormal karyotype in patients with spermatogenesis disorders. The incidence of AZF microdeletion was higher in patients with spermatogenic disorders than normal males, suggesting that AZF microdeletion may play a role in spermatogenesis; the b2/b3 deletion could be related to male infertility, which may involve the DAZ3/DAZ4 deletion.