Estrogen receptor alpha promoter polymorphism: stronger estrogen action is coupled with lower sperm count.
BACKGROUND
Although the importance of estrogens in male reproduction is indisputable, little attention has been paid to the role of estrogen receptor (ER) gene mutations in male infertility. Significant correlation between (TA)n repeat allelic variants and lumbar bone mineral density was previously observed in the promoter region of the ERalpha gene, indicating that allelic combinations with higher number of (TA)n repeats are functionally more active genetic variants.


METHODS
We studied the (TA)n repeat polymorphism situated in the promoter region of the ERalpha gene in a large group of infertile and normospermic men (n = 347).


RESULTS
Although the (TA)n polymorphism failed to show a significant association with male infertility, we found a significant effect of this polymorphism on sperm count. In the group of infertile men, the mean TA repeat number and sperm concentration (P = 0.022) and total sperm number (P = 0.043) were inversely correlated, showing an association between higher TA repeat number (genotype A) and lower sperm production. In line with this observation, normospermic subjects with genotype A had a significantly lower mean sperm concentration with respect to men bearing genotype B with shorter TA alleles (P < 0.05) and a lower total sperm count (P < 0.01).


CONCLUSIONS
Our data indicate that specific allelic combinations of the ERalpha, which confer a stronger estrogen effect, may negatively influence human spermatogenesis.
Guarducci
Elena
E
Department of Clinical Physiopathology, Andrology Unit, University of Florence, Florence, Italy.
Nuti
Francesca
F
Becherini
Lucia
L
Rotondi
Mario
M
Balercia
Giancarlo
G
Forti
Gianni
G
Krausz
Csilla
C
D000483:Alleles; D001483:Base Sequence; D004247:DNA / Q000737:chemistry; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000502:physiology; D004967:Estrogens / Q000502:physiology; D005838:Genotype; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013076:Sperm Count; D013091:Spermatogenesis / Q000502:physiology
D047628:Estrogen Receptor alpha; D004967:Estrogens; D004247:DNA