Volume 28, Issue 9 (12-2021)
RJMS 2021, 28(9): 45-57 |
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Research code: 91000427
Ethics code: IR.ACECR.ROYAN.REC.1395.1
Clinical trials code: 0
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Zamanian M, Asadi F, Sedighi Gilani M A, Ghaheri A, Borjian Boroujeni P. Evaluation and comparison of the frequency of Y-chromosome microdeletions in different ethnicities of Iranian infertile men. RJMS 2021; 28 (9) :45-57
URL: http://rjms.iums.ac.ir/article-1-6486-en.html
URL: http://rjms.iums.ac.ir/article-1-6486-en.html
Mohammadreza Zamanian 
, Fahimeh Asadi , Mohammad Ali Sedighi Gilani , Azadeh Ghaheri , Parnaz Borjian Boroujeni
, Fahimeh Asadi , Mohammad Ali Sedighi Gilani , Azadeh Ghaheri , Parnaz Borjian Boroujeni
Reproductive Sciences Center, Royan Institute, Academic Center for Education, Culture and Research, Tehran, Iran , zamanzss@gmail.com
Abstract: (1544 Views)
Background & Aims: Infertility means that a couple does not become fertile after one year of sexual intercourse, which is faced by 10-15% of young couples, and in 50% of cases it is related to male defects. The spermatogenesis genes involved in male fertility are located in the proximal region of the long arm of the Y chromosome (Yq11) in the azoospermia factor region, which includes the AZFa, AZFb, and AZFc subunits. Microdeletion in AZF regions causes changes in testicular histology from Sertoli Cell Only Syndrome to hypospermatogenesis. Yq microdeletions are the most common molecular cause of male infertility and include three regions: AZFα, AZFb and AZFc. These regions contain different genes involved in spermatogenesis. Yq microdeletions have been reported in 5-10% of infertile men and 6-16% of azoospermic men. In some other studies, the prevalence of these microdeletions has been reported in 20 to 30% of patients with non-obstructive azoospermia and in 3 to 7% of patients with severe idiopathic oligospermia. So far, ethnic patterns in the distribution of these microdeletions in the Iranian infertile male population have not been extensively studied. Accordingly, considering that Iran is a geographically vast country and has a high population / ethnic diversity, the present study aims to investigate the overall prevalence of these microdeletions in the population of Iranian infertile men and compare its frequency distribution in it was designed and implemented between different ethnicities.
Methods: In this study 1887 infertile men with severe oligospermia or azoospermia were referred to the Royan Institute beween 1391 to 1392 were evaluated for the presence of Yq microdeletions. At first, DNA was extracted from the peripheral blood by salting out method and multiplex PCR was performed based on the determination of six different STS markers. To identify Yq microdeletions in three regions of AZFa, AZFb and AZFc, six STS markers were used inside two separate mixes. Two STS markers were considered for each AZF region and sY14 marker was used to examine the SRY gene and the ZFX / ZFY marker were used as internal controls. Information about semen analysis (Spermogram) and the results of patients' hormonal tests for the three hormones LH, FSH and testosterone were also extracted from their files. The ethnic segregation and classification of the Iranian male population was based on latest version of the Encyclopaedia Britannica (2010) book from the Statistics Center of Iran. Accordingly, the men studied in this study were classified into the ethnicities mentioned in the Table 1. For the appointment of ethnicity in each of the men under this study, the place of birth and dialect of three consecutive generations of clients were determined and then were placed in one of the seven ethnic groups including Fars, Azeri (Turkish), Kurdish, Lor, Gilak/ Mazeni (northern), Arabic And non-Iranians (Afghans and Iraqis).
Results: Among the 1887 studied infertile men, 100 were diagnosed with microdeletions (5.29%), 69 patients (68.3%) had azoospermia and 31 patients (30.6%) had severe oligospermia. Among men with microdeletions, 70% had deletion in AZFc, 25.4% had deletion in AZFb and 4.6% had deletion in AZFa. Combined deletions of AZFbc were observed in 18 patients and AZFabc in three patients. All men with AZFa, AZFb, AZFc, AZFbc, and AZFabc regions had non-obstructive azoospermia, and only men with AZFc and AZFb microdeletions showed evidence of sperm production. Among the patients with microdeletions, 47 patients (46.5%) had normal hormone levels, 22 patients (21.7%) had higher than normal levels of FSH, two patients had high levels of LH and 14 patients (13.8%) had high levels of both LH and FSH. The results of hormonal tests were not available in 16 of them. Ethnic distribution in 100 patients showed that 38% were Azeri, 30% Persian, 11% Kurdish, 8% Lor, 6% Gilak/ Mazani, 2% Arab and 5% Iraqi and Afghan nationals. The results of chi-square test showed that the distribution of different Y chromosome microdeletions is not uniform among Iranian ethnicities (p <0.001).
Conclusion: Ethnic and racial differences can also be influential factors in the prevalence of these microdeletions, which we examined in the present study. Such a complete study of Iranian ethnicities has not been done before, and in other parts of the world, studies have not usually been aimed at comparing ethnicities. The overall frequency and distribution pattern of Yq microdeletions in the population of Iranian infertile men is similar to other populations in the world. The pattern of distribution of different microdeletions among different Iranian ethnicities seems to be similar. This means that in all ethnicities that accounted for a significant number of deletion patients (Turks, Fars, and Kurds), Yq microdeletions were most common in the AZFc region. After that, AZFb and AZFa were more frequent, respectively. In fact, ethnicity did not have a significant effect on the distribution of these microdeletions and no significant results were observed in this regard. Regarding the frequency of different microdeletions (frequency of distribution) in various Iranian ethnicities, considering that the number of samples of some microdeletions in some ethnicities was less than the amount required for statistical analysis, the number of people studied in each ethnicity has been adjusted. Statistical analysis of these results using chi-square test showed that the frequency of microdeletions in ethnicities is not uniform (p <0.001), therefore, the ethnicity of the Iranian infertile man is influential in the frequency of distribution of these microdeletions. However, due to the insufficient number of people with microdeletions in some ethnicities, it is not possible to determine with sufficient statistical accuracy which microdeletions occurs more frequently in which ethnicity. In this regard, it seems that the referral of Royan Infertility Treatment Center and the existence of infertility treatment centers in the centers of some provinces have affected the ethnic composition of the client. Therefore, it is suggested that in future and supplementary studies, in order to create an appropriate ethnic distribution in the referring population, while increasing the sample size (especially for some ethnicities) if possible with the cooperation of infertility treatment centers in other provinces, comprehensive studies in this regard be used to achieve a more definite result in this regard.
Methods: In this study 1887 infertile men with severe oligospermia or azoospermia were referred to the Royan Institute beween 1391 to 1392 were evaluated for the presence of Yq microdeletions. At first, DNA was extracted from the peripheral blood by salting out method and multiplex PCR was performed based on the determination of six different STS markers. To identify Yq microdeletions in three regions of AZFa, AZFb and AZFc, six STS markers were used inside two separate mixes. Two STS markers were considered for each AZF region and sY14 marker was used to examine the SRY gene and the ZFX / ZFY marker were used as internal controls. Information about semen analysis (Spermogram) and the results of patients' hormonal tests for the three hormones LH, FSH and testosterone were also extracted from their files. The ethnic segregation and classification of the Iranian male population was based on latest version of the Encyclopaedia Britannica (2010) book from the Statistics Center of Iran. Accordingly, the men studied in this study were classified into the ethnicities mentioned in the Table 1. For the appointment of ethnicity in each of the men under this study, the place of birth and dialect of three consecutive generations of clients were determined and then were placed in one of the seven ethnic groups including Fars, Azeri (Turkish), Kurdish, Lor, Gilak/ Mazeni (northern), Arabic And non-Iranians (Afghans and Iraqis).
Results: Among the 1887 studied infertile men, 100 were diagnosed with microdeletions (5.29%), 69 patients (68.3%) had azoospermia and 31 patients (30.6%) had severe oligospermia. Among men with microdeletions, 70% had deletion in AZFc, 25.4% had deletion in AZFb and 4.6% had deletion in AZFa. Combined deletions of AZFbc were observed in 18 patients and AZFabc in three patients. All men with AZFa, AZFb, AZFc, AZFbc, and AZFabc regions had non-obstructive azoospermia, and only men with AZFc and AZFb microdeletions showed evidence of sperm production. Among the patients with microdeletions, 47 patients (46.5%) had normal hormone levels, 22 patients (21.7%) had higher than normal levels of FSH, two patients had high levels of LH and 14 patients (13.8%) had high levels of both LH and FSH. The results of hormonal tests were not available in 16 of them. Ethnic distribution in 100 patients showed that 38% were Azeri, 30% Persian, 11% Kurdish, 8% Lor, 6% Gilak/ Mazani, 2% Arab and 5% Iraqi and Afghan nationals. The results of chi-square test showed that the distribution of different Y chromosome microdeletions is not uniform among Iranian ethnicities (p <0.001).
Conclusion: Ethnic and racial differences can also be influential factors in the prevalence of these microdeletions, which we examined in the present study. Such a complete study of Iranian ethnicities has not been done before, and in other parts of the world, studies have not usually been aimed at comparing ethnicities. The overall frequency and distribution pattern of Yq microdeletions in the population of Iranian infertile men is similar to other populations in the world. The pattern of distribution of different microdeletions among different Iranian ethnicities seems to be similar. This means that in all ethnicities that accounted for a significant number of deletion patients (Turks, Fars, and Kurds), Yq microdeletions were most common in the AZFc region. After that, AZFb and AZFa were more frequent, respectively. In fact, ethnicity did not have a significant effect on the distribution of these microdeletions and no significant results were observed in this regard. Regarding the frequency of different microdeletions (frequency of distribution) in various Iranian ethnicities, considering that the number of samples of some microdeletions in some ethnicities was less than the amount required for statistical analysis, the number of people studied in each ethnicity has been adjusted. Statistical analysis of these results using chi-square test showed that the frequency of microdeletions in ethnicities is not uniform (p <0.001), therefore, the ethnicity of the Iranian infertile man is influential in the frequency of distribution of these microdeletions. However, due to the insufficient number of people with microdeletions in some ethnicities, it is not possible to determine with sufficient statistical accuracy which microdeletions occurs more frequently in which ethnicity. In this regard, it seems that the referral of Royan Infertility Treatment Center and the existence of infertility treatment centers in the centers of some provinces have affected the ethnic composition of the client. Therefore, it is suggested that in future and supplementary studies, in order to create an appropriate ethnic distribution in the referring population, while increasing the sample size (especially for some ethnicities) if possible with the cooperation of infertility treatment centers in other provinces, comprehensive studies in this regard be used to achieve a more definite result in this regard.
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