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Hum. Reprod. Advance Access originally published online on April 29, 2004
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Human Reproduction, Vol. 19, No. 6, 1426-1430, June 2004
© 2004 European Society of Human Reproduction and Embryology

Associations between androgen receptor CAG repeat length and sperm morphology*

David Milatiner, David Halle1, Michael Huerta, Ehud J. Margalioth, Yoram Cohen, Avraham Ben-Chetrit, Michael Gal, Tzvia Mimoni and Talia Eldar-Geva2

IVF Unit, Shaare-Zedek Medical Center, Ben Gurion University of the Negev, Jerusalem 91031, Israel

The first two authors contributed equally to the paper.

1 Current address: Bioinformatic Department, Jerusalem Center of Technology, Jerusalem, Israel

2 To whom correspondence should be addressed at: IVF Unit, Shaare-Zedek Medical Center, P.O.Box 3235, Jerusalem 91031, Israel. e-mail: gevat{at}szmc.org.il

BACKGROUND: The number of (trinucleotide) CAG repeats within the androgen receptor (AR) gene is inversely correlated with transcriptional activity of testosterone-target genes. Although abnormally long CAG repeats are strongly associated with male infertility, it is unclear whether CAG repeat length polymorphism can affect androgen receptor activity and sperm parameters. To explore the previously suggested association between CAG repeats and male fertility, we conducted this prospective cohort study. METHODS: We enrolled 172 men attending the IVF unit in Shaare-Zedek Medical Center. Sperm concentration, motility and morphology and the number of CAG repeats in the AR gene were measured. RESULTS: Mean CAG repeat length was greater in teratozoospermia (<14% normal forms, strict criteria) than in the normal morphology group [mean ± 95% confidence interval (CI) 22.19 ± 0.38 versus 21.25 ± 0.28, P = 0.02]. Logistic regression models showed that longer CAG repeats were associated with abnormal sperm morphology [odds ratio for percentage of normal forms per unit increase in CAG repeat length 1.14 (95% CI 1.01–1.28), P = 0.04]. No association was found between CAG repeat length and sperm concentration or motility. CONCLUSIONS: We found a positive correlation between CAG repeat length and teratozoospermia. This finding validates the concept that AR function is inversely regulated by length of its CAG repeat tract.

Key words: androgen receptor gene/CAG repeat length/male subfertility/sperm morphology/teratozoospermia

* Presented in part at the 19th Annual Meeting of the ESHRE (O-023), Madrid, Spain, 29 June–2 July 2003 (Abstract).


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