Quantitative trait analysis suggests polymorphisms of estrogen-related genes regulate human sperm concentrations and motility.

BACKGROUND Human spermatogenesis is regulated by complex networks, and estrogens are recognized as one of the significant regulators of spermatogenesis. We tested the associations between variants of estrogen-related genes and semen parameters. METHODS We performed genotyping for genetic variants of estrogen-related genes and quantitative trait analysis of fertile and infertile men with well-characterized reproductive phenotypes. Men with known semen parameters (n= 677) were enrolled, including 210 fertile men and 467 infertile men. A total of 17 genetic markers from 10 genes, including 2 estrogen receptors (ER-α, ER-β), 7 estrogen synthesizing/metabolizing genes (CYP19A1, HSD17B1, CYP1A1, CYP1B1, COMT, GSTM1, GSTT1) and 1 transport gene (SHBG) were genotyped. Sperm concentration, motility and morphology were taken as quantitative traits to correlate with genetic variants in the estrogen-related genes. RESULTS Five genes (rs1801132 and rs2228480 of the ER-α gene, rs1256049 and rs4986938 of the ER-β gene, rs605059 of the HSD17B1 gene, rs1799941 of the SHBG gene and rs1048943 and rs4646903 of the CYP1A1 gene) were found to be significantly associated with sperm concentration (P< 0.01), while five genes (rs1801132 of the ER-a gene, rs1256049 of the ER-β gene, rs1048943 of the CYP1A1 gene, rs605059 of the HSD17B1 gene and rs1799941 along with rs6259 of the SHBG gene) were associated with sperm motility (P< 0.01). None of the estrogen-related genes were associated with sperm morphology. With an increasing number of risk alleles, sperm concentration and motility tended to deteriorate and show a loci-dosage effect. CONCLUSIONS Quantitative trait analysis based on a limited number of genetic markers suggests that estrogen-related genes mainly regulate sperm concentration and motility.