| Infertility refers to couples who have not become pregnant after at least1year of unprotected intercourse. Over many years in early20th century the majority if not all of human societies believed that infertility always is a woman’s problem. But nowadays there is a clear fact that male factors contributed about half of infertility cases. Regarding the possible causes of infertility, wide range of disorders ranging from genetic disorders to coital problems can influence male fertility. Among these genetic aberrations were considered as one of the most frequent and interesting causes, that contributed about30%causes of infertile male, involving both chromosomal disorders and single gene mutations.Genetic disorders that influence male fertility including two major groups as follow:chromosomal abnormalities which characterized by abnormal karyotype, including sex chromosome abnormalities, and autosomal chromosomal abnormalities. The second type of genetic disorders is referred to Y chromosome microdeletions which characterized by azoospermia factor gene deletions. The clinical phenotype of infertile men with genetic aberrations is of wide variety, in some cases infertile men attend the reproductive clinic with completely absent of sperm in the ejaculated semen (azoospermia), other cases showed small amount of sperm in their ejaculated semen. Why infertile men with genetic aberrations have specific clinical phenotype? What’s the relationship between abnormal semen quality and genetic disorders? To answer these questions, we investigated1384infertile men from Northeast of China. These patients were divided into693azoospermic patients and691patients with poor semen quality by semen analysis. Other50normal fertile men aged24-37years old were included as control. Karyotype analysis was done by using G-banding method and Y chromosome microdeletion was detected by using polymerase chain reaction assay PCR. Moreover, hormone level was tested by eleterocheiluminescence immunoassays. All the clinical and lab results were analyzed to illuminate the relationship between abnormal semen quality and genetic disorders. This study was approved by the ethics committee of the First Bethune Hospital of Jilin University.Results:1. Associated results of azoospermic men1.1Abnormal karyotype among infertile azoospermic patients in Northeast China was detected at a rate of23.52%(163/693). Of these, Klinefelter syndrome (KS) is the most frequent (17.75%of the azoospermic patients), followed by Chromosome polymorphism (3.32%), and Translocation (0.72%).1.2The volumes testis of Klinefelter syndrome and Translocation carriers were significantly smaller than those of control fertile males in azoospermic group, respectively, while no significant difference was noted in those of Polymorphic, and inversion group when compared with control.1.3The levels of inhibin B of seminal plasmal of Polymorphic and Klinefelter syndrome azoospermic patients were significantly lower than those of control fertile males, respectively. Moreover, the level of Fructose in Translocation group was found significantly higher than those of control fertile males. No significant difference was noted in different biochemical of seminal plasma of other azoospermic abnormal karyotype patients compared with those of azoospermic of Klinefelter syndrome carners.1.4FSH, LH and E2hormones levels of Polymorphic and Klinefelter syndrome azoospermic patients were significantly higher than those of control, respectively, while no significant difference of PRL, FSH, LH and E2levels was found between Translocation/Inversion and control group. Interesting, T hormone and T/LH ratio of all chromosomal abnormalities among azoospermic patients were significantly lower than those of control.1.5The incidence of Y chromosome microdeletion was found at a rate of7.94%(55/693) among azoospermic patients. AZFc is most deleted region, and the most frequent deletion pattern is deletion of sY152, sY255and sY254.Additionally, most of deletions were de novo mutations, but some of cases were inherited from their fathers.1.6The testicular volumes of AZFc azoospermic deletions patient were significantly smaller, and the levels of Fructose and a-glucosidase of AZFc deletions were significantly higher than those of control fertile males. Moreover, the levels of Inhibin B of patients with AZFc, AZFb+c, and AZFb deletions were significantly lower than those of control, respectively.1.7FSH levels of patients with AZFc, AZFb+c, and AZFb deletions, LH level of patients with AZFc deletions and PRL level of patients with AZFc and AZFb deletions were significantly higher, while T and T/LH ratio of patients with AZFc, AZFb+c, and AZFb deletions were significantly lower than those of control.2. Associated results of patients with poor semen quality2.1Abnormal karyotype among patients with poor semen quality in Northeast China was detected at a rate of12.01%(83/691). Of these, Klinefelter syndrome is the most frequent (4.49%of the patients with poor semen quality), followed by Chromosome polymorphism (3.76%), and Translocation (3.18%).2.2The volumes testis of Klinefelter syndrome and Translocation carriers were significantly smaller than those of control fertile males in poor semen quality groups, respectively, while no significant difference was noted in those of Polymorphic group compared with control.2.3FSH and LH hormones levels of Klinefelter syndrome patients with poor semen quality were significantly higher than those of control, while in Polymorphism patients, only FSH level were significantly higher than those of control. T hormone and T/LH ratio of all chromosomal abnormalities among poor semen quality patients were significantly lower than those of control.2.4Non-moisaic Klinefelter syndrome men with poor semen quality were all oligozoospermic and cryptozoospermic. Compared with control, all these patients showed smaller testis volume, higher FSH and LH and lower T and T/LH.2.5The incidence of Y chromosome microdeletion was found at a rate of5.50%(38/691) among patients with poor semen quality. AZFc is most deleted region, and the most frequent deletion pattern is also deletion of sY152, sY255and sY254. All the deletions which referred in pedigree study were de novo mutation.2.6Compared with control and without AZF deletion group, poor semen quality patients with AZF deletion showed smaller testis volume, higher FSH and LH and lower T and T/LH.3. Comparison between azoospermic and poor-semen quality patients3.1The incidence of abnormal karyotype among infertile azoospermic patients compared with that of poor semen quality patients is significantly higher, while the incidence of Y chromosome microdeletion was found to be not statistically different from that among poor semen quality patients.3.2Compared with corresponding patients with poor semen quality, the age and testis volumes of all azoospermic group, including group of azoospermia with genetic factor and group of azoospermia without genetic factor, were significantly smaller.3.3Compared with corresponding patients with poor semen quality, the levels of a-glycosidase of azoospermia, and azoospermia with genetic factor patients were significantly lower. However, there was no statistically different was noted in levels of inhibin B and Fructose.3.4Compared with corresponding patients with poor semen quality, the levels of FSH, LH were significantly higher in all azoospermic patients of different etiology. No significant difference was noted in PRL, T and E2levels.3.5Compared with group of azoospermia without genetic factor, the age and testis volumes were smaller, the level of Fructose, a-glucosidase, FSH and LH were higher, and the level of T and T/LH were lower in azoospermic patients with genetic factor. No significant difference was noted on inhibin B, PRL and E2levels.3.6Compared with group of poor-semen without genetic factor, no significant difference was noted about age, testis volumes, biochemicals of seminal plasma, inhibin B and hormone levels in group of poor-semen with genetic factor.Conclusions1. In Northeast of China, important genetic factor of azoospermic patients were Klinefelter syndrome and Y chromosome microdeletion. Klinefelter syndrome patients suffered from smaller testis, higher FSH and LH, and lower T and T/LH than other abnormal karyotype carriers. In addition, the azoospermic patients with Y chromosome microdeletions had similar sex hormones abnormality as KS patients.2. In Northeast of China, genetic factors of patients with poor semen quality were diverse. Y chromosome microdeletion played the most important role for causing poor semen quality. Almost all this kind of patients had gene microdeletion in the AZFc region, and these deletions were derived from de novo mutation.3. Compared with Y chromosome microdeletion, abnormal karyotype tends to cause azoospermia. Genetic disorder may leads to azoospermia by elevated FSH, LH and low T. Moreover, the extent of dyszoospermia was closely association with the value of FSH, LH and T. |
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