Tumor necrosis factor-alpha -308 polymorphism in infertile men with altered sperm production or motility.
BACKGROUND
One of the most well-documented cytokines suspected as a hazard to male fertility is tumor necrosis factor-alpha (TNFalpha). Genetic factors such as single-nucleotide polymorphisms (SNPs) in the TNF gene cluster impact TNFalpha levels. Our objective was to establish the potential involvement of -308 TNF SNP in male infertility risk.


METHODS
In 684 infertile male patients undergoing an intracytoplasmic sperm injection procedure, we used allele-specific polymerase chain reaction (PCR) and PCR-RFLP to investigate the distribution of the guanine (G)-to-adenosine (A) substitution at position -308 in the promoter region of the TNFalpha gene.


RESULTS
An increased frequency of the -308 TNFalpha A allele was found in patients with low sperm count of testicular origin [P = 0.002; odds ratio (OR) = 2.93] or with normal production count but altered sperm motility (P = 0.003; OR = 2.32), compared with a patient group with normal sperm count and quality (morphology and motility). In patients with low sperm count exhibiting TNFalpha A allele, compared with those with G allele, an alteration in hormonal balance was observed with increased inhibin B levels and subsequent reduced FSH plasma levels, leading to an FSH/inhibin B ratio roughly half as high (from 0.07 +/- 0.01 in TNFA versus 0.13 +/- 0.02 in TNFG allele groups, P < 0.0001).


CONCLUSIONS
As the -308 TNFalpha A allele has been associated with an increased expression/production of TNFalpha, the potential use of therapies based on inhibition of TNFalpha activities could represent possible therapeutic opportunities for patients with low sperm count (i.e. primary testicular dysfunction) or with altered sperm motility.
Tronchon
V
V
INSERM, U407, Oullins, France.
Vialard
F
F
El Sirkasi
M
M
Dechaud
H
H
Rollet
J
J
Albert
M
M
Bailly
M
M
Roy
P
P
Mauduit
C
C
Fenichel
P
P
Selva
J
J
Benahmed
M
M
D000328:Adult; D053627:Asthenozoospermia / Q000235:genetics; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D007265:Inhibins / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D009845:Oligospermia / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D020554:Sperm Injections, Intracytoplasmic; D013081:Sperm Motility; D013739:Testosterone / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D012738:Sex Hormone-Binding Globulin; D014409:Tumor Necrosis Factor-alpha; C422364:inhibin B; D013739:Testosterone; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone