UroToday.com - Though the mechanism of human reproductive physiology is understood, the underlying causes of male subfertility are not yet fully elucidated1 due to the complex nature of disease. The male partner is responsible, or contributes to approximately 50% of the couples that are unable to conceive spontaneously. Most genetic studies on male infertility have given special attention to the Y chromosome as most of the genes show testis specific expression. The role of autosomal and X chromosome genes have not gained ample evidence, though it has been suggested that up to 60% of undiagnosed male infertility arises due to mutations in autosomal genes.2 Therefore, our objective was to analyze an autosomal gene (14q); Ostrogen Receptor beta (ERbeta) and explore whether polymorphisms in that gene play any role in causing infertility in Indian men. The ERbeta gene has been shown to play role in human reproduction3, which is considerably different from the role of ERalpha and has not been studied extensively for its role in infertility in males.

As CA repeat polymorphism in ERbeta has not been analyzed for its role in male infertility and RsaI AG (rs1256049; c.1082:G>A) genotype frequency was found to be approximately 3 times higher in Caucasian infertile men4, we have investigated both the polymorphisms in Indian men to find out their organization with infertility. Our analysis revealed that both the polymorphisms are not associated with infertility in Indian men. The difference in our results from Aschim et al. (2005) could be attributed to the different ethnic origin of these two populations. Although the combined analysis

of CA repeat and RsaI polymorphisms by haplotyping did not show any specific haplotype associated with male infertility, it was interesting to note that the RsaI A allele was nearly absent with longer CA repeats (24 or more CA). The implications of that observation require support from several such studies. The non organization of CA repeat and RsaI polymorphisms with infertility in Indian men does not rule out the role of ERbeta in male infertility and requires further analysis of the whole ERbeta gene, which is being carried out in our laboratory.

1. References Meschede D, Horst J: Themolecular genetics of male infertility. Mol Hum Reprod 1997; 3: 419.

2. Lilford R, Jones AM, Bishop DT, Thornton J and Mueller R: Case-control study of whether subfertility in men is familial. British Medical Journal 1994; 309: 570.

3. Saunders PT: Does estrogen receptor beta play a significant role in human reproduction? Trends in Endocrinology and Metabolism 2005; 16: 222.

4. Aschim EL, Giwercman A, Stahl O, Eberhard J, Cwikiel M, Nordenskjold A, Haugen TB, Grotmol T and Giwercman YL: The RsaI polymorphism in the estrogen receptor-beta gene is associated with male infertility. The Journal of Clinical Endocrinology and Metabolism 2005; 90: 5343.

Written by Arun Khattri, MD, Lalji Singh,MD and Kumarasamy Thangaraj, MD, as part of Beyond the Abstract on UroToday.com. that initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc… of their research by referencing the published abstract.

Original post by Mallows