Does intracytoplasmic sperm injection lead to a rise in the frequency of microdeletions in the AZFc region of the Y chromosome in future generations?
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 answer 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 for fitness (0.5) and spontaneous mutation frequency (0.0001), the maximum increase in men with microdeletions would 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 would 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.
Kremer
J A
JA
Department of Obstetrics and Gynaecology, University Hospital Nijmegen St Radboud, The Netherlands.
Tuerlings
J H
JH
Borm
G
G
Hoefsloot
L H
LH
Meuleman
E J
EJ
Braat
D D
DD
Brunner
H G
HG
Merkus
H M
HM
D002872:Chromosome Deletion; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects* / Q000379:methods; D005787:Gene Frequency; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008433:Mathematics; D008845:Microinjections; D008957:Models, Genetic; D009154:Mutation; D009845:Oligospermia / Q000235:genetics* / Q000628:therapy*; D011247:Pregnancy; D012307:Risk Factors; D013094:Spermatozoa; D014998:Y Chromosome