Polymorphisms in cell death pathway genes are associated with altered sperm apoptosis and poor semen quality.
BACKGROUND
The FAS/FASLG system has been proposed to play a key role in germ cell apoptosis. To elucidate the role of the genetic variants of cell death pathway genes in male infertility, we genotyped the polymorphisms of FAS, FASLG and caspase-8 (CASP8) genes and evaluated their effects on sperm apoptosis and semen quality in infertile men.


METHODS
The genotypes of FAS, FASLG and CASP8 were determined in 620 infertile men. Sperm apoptosis rates were measured by terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP nick end labelling (TUNEL) assay, and the semen quality analysis was performed using computer assisted sperm analysis.


RESULTS
We found that polymorphisms of FAS-670A/G (rs1800682: A>G) and CASP8-652 6N ins/del (rs3834129: -/CTTACT) were associated with sperm apoptosis and semen quality. Individuals with FAS-670GG showed low apoptosis rate and decreased sperm concentration, compared with the FAS-670AA genotype. Similarly, in comparison with the CASP8-652 6N ins/ins genotype, the CASP8-652 6N (ins/del+del/del) genotypes also showed significantly decreased sperm apoptosis rate and poor sperm motility. Other polymorphisms investigated did not appear to affect sperm apoptosis and semen quality.


CONCLUSIONS
This study showed for the first time that functional variants of FAS and CASP8 might contribute to the dysfunctional apoptotic mechanism in germ cells, which could result in poor semen quality of ejaculated sperm.
Ji
Guixiang
G
Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.
Gu
Aihua
A
Hu
Fan
F
Wang
Shoulin
S
Liang
Jie
J
Xia
Yankai
Y
Lu
Chuncheng
C
Song
Ling
L
Fu
Guangbo
G
Wang
Xinru
X
D017209:Apoptosis / Q000235:genetics*; D053181:Caspase 8 / Q000235:genetics; D005838:Genotype; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D055101:Semen Analysis; D013081:Sperm Motility; D013094:Spermatozoa / Q000166:cytology* / Q000502:physiology; D019014:fas Receptor / Q000235:genetics
C491901:FAS protein, human; D019014:fas Receptor; C505530:CASP8 protein, human; D053181:Caspase 8