Does intracytoplasmic sperm injection lead to a rise in the frequency of microdeletions in the AZFc region of the Y chromosome in future generations?

被引:11
作者
Kremer, JAM
Tuerlings, JHAM
Borm, G
Hoefsloot, LH
Meuleman, EJH
Braat, DDM
Brunner, HG
Merkus, HMWM
机构
[1] Univ Nijmegen St Radboud Hosp, Dept Obstet & Gynaecol, NL-6500 HB Nijmegen, Netherlands
[2] Univ Nijmegen St Radboud Hosp, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands
[3] Univ Nijmegen St Radboud Hosp, Dept Biometr, NL-6500 HB Nijmegen, Netherlands
[4] Univ Nijmegen St Radboud Hosp, Dept Urol, NL-6500 HB Nijmegen, Netherlands
关键词
AZF; future; ICSI; microdeletion; Y chromosome;
D O I
10.1093/humrep/13.10.2808
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
Microdeletions in the AZFc region of the Y chromosome are found in oligo- and azoospermic men, These mutations were genetically lethal before the intracytoplasmic sperm injection (ICSI) era but they can nowadays be transmitted to next generations via ICSI, We have tried to ans,per the question,'Does ICSI lead to a significant rise in the frequency of these microdeletions in future generations?', by developing a mathematical model for Y-linked mutations with two variables (fitness and mutation frequency), To illustrate this model we have made estimates according to three imaginary scenarios, Using the assumptions described, the model predicted that the frequency of microdeletions in the AZFc region would increase in each generation until a plateau was reached, The higher the fitness, the higher the plateau and the later the plateau would be reached. Taking realistic estimates fur fitness (0.5) and spontaneous mutation frequency (0.0001), the maximum increase in men with microdeletions mould be twofold, This maximum would be already reached after five generations, However, if the fitness of these men were improved and approached 1.0, the mechanism of selection would disappear and finally all men mould have the deletion in the AZFc region, Because of the assumptions in these scenarios, these estimates have limitations, The model presented shows that the rise in the frequency of men with microdeletions in the AZFc region in future generations would be limited as long as the fitness of these men remained limited.
引用
收藏
页码:2808 / 2811
页数:4
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