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Hum. Reprod. Advance Access originally published online on January 5, 2006
Human Reproduction 2006 21(4):994-1001; doi:10.1093/humrep/dei439
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Estrogen receptor {alpha} promoter polymorphism: stronger estrogen action is coupled with lower sperm count

Elena Guarducci1, Francesca Nuti1, Lucia Becherini1, Mario Rotondi2, Giancarlo Balercia3, Gianni Forti1 and Csilla Krausz1,4

1 Department of Clinical Physiopathology, Andrology Unit, 2 Endocrinology Unit, University of Florence, Florence and 3 Division of Endocrinology, Institute of Internal Medicine Polytechnic University of Marche, Ancona, Italy

4 To whom correspondence should be addressed at: Andrology Unit, Viale Pieraccini 6, Florence 50139, Italy. E-mail: c.krausz{at}dfc.unifi.it

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 ER{alpha} 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 ER{alpha} 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 ER{alpha}, which confer a stronger estrogen effect, may negatively influence human spermatogenesis.

Key words: estrogen receptor/genetics/male infertility/polymorphism/spermatogenesis


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