Association of TUSC1 and DPF3 gene polymorphisms with male infertility.

PURPOSE: Recently, genome-wide association studies of a Hutterite population in the USA revealed that five single nucleotide polymorphisms (SNPs) with a significant association with sperm quality and/or function in ethnically diverse men from Chicago were significantly correlated with family size. Of these, three SNPs (rs7867029, rs7174015, and rs12870438) were found to be significantly associated with the risk of azoospermia and/or oligozoospermia in a Japanese population. In this study, we investigated whether the rs10966811 (located in an intergenic region between the TUSC1 and IZUMO3 genes) and rs10129954 (located in the DPF3 gene) SNPs, previously related to family size, are associated with male infertility. In addition, we performed association analysis between rs12348 in TUSC1 and rs2772579 in IZUMO3 and male infertility. METHODS: We genotyped 145 patients with infertility (including 83 patients with azoospermia and 62 with oligozoospermia) and 713 fertile controls by PCR-RFLP technique for polymorphism. Because rs10966811 has no restriction sites, the SNP rs12376894 with strong linkage disequilibrium was selected as an alternative to rs10966811. RESULTS: There was a statistically significant association between rs12376894 proxy SNP of rs10966811 and oligozoospermia. Also, a statistically significant association between rs10129954 and azoospermia, and oligozoospermia was observed. When we assessed the relationship between rs12348 in TUSC1 and rs2772579 in IZUMO3 and male infertility traits, we found that rs12348 in TUSC1 was significantly associated with azoospermia and oligozoospermia, but rs2772579 in IZUMO3 was not associated with male infertility. CONCLUSION: We found that the polymorphisms in TUSC1 and DPF3 displayed strong associations with male infertility.

Androgen-independent growth in LNCaP cell lines and steroid uridine diphosphate-glucuronosyltransferase expression.

AIM: To investigate the mechanism of androgen-independent growth of prostate cancer after androgen ablation in LNCaP cells and the effect of glucuronidation activity. METHODS: To establish androgen-independent growth in prostate cancer LNCaP-SF, continuous passage was performed in androgen-stripped medium and the cells were evaluated for glucuronidation activity. The expression vector of antisense uridine diphosphate glucuronosyl-transferase (UGT) 2B15 cDNA was also constructed and evaluated. RESULTS: LNCaP-SF lead to a higher expression in UGT2B15 and their glucuronidation activity is 2.5 times higher than that of LNCaP cells. Significantly fewer LNCaP and LNCaP-SF than control were transfected with the antisense UGT2B15 cDNA, suggesting that UGT2B15 plays an important part in the glucuronidation activity of androgens in both cells. CONCLUSION: The alteration of UGT2B15 expression in LNCaP-SF cells is proposed as a biological characteristic involved in the growth of hormone-refractory prostate cancer.

Differential expression of 17beta-hydroxysteroid dehydrogenase isozyme genes in prostate cancer and noncancer tissues.

BACKGROUND: The adrenal steroids dehydroepiandrosterone and androstenediones are converted into active androgen testosterone in prostatic tissues. Different 17beta-hydroxysteroid dehydrogenase (17betaHSD) isozymes are characterized by either oxidation or reduction reactions. These redox reactions represent an important step in both biosynthesis and metabolism of androgens. This study presents the differential expression of 17betaHSD isozyme genes in cancerous and noncancerous prostate tissues of in vivo samples. METHODS: Thirty-four fresh specimens of transrectal prostatic needle biopsy were obtained; 11 were pathologically diagnosed as adenocarcinoma and 23 as without malignancy. The gene expression levels of five isozymes (type 1-5) of 17betaHSD were evaluated. The quantification of gene expression was assessed by means of the real-time polymerase chain reaction. RESULTS: The expression levels of the type 3 17betaHSD gene with malignancy were significantly higher than those in prostatic tissues without malignancy, and those of type 2 17betaHSD with malignancy were significantly lower than those in nonmalignant tissues. There were no significant differences in 17betaHSD type 1, type 4, and type 5 gene expression in cancerous and noncancerous tissues. CONCLUSION: Our results suggest that 17betaHSD type 2 and type 3 play an important role in the conversion of adrenal steroids into potential androgens in prostate cancer tissue.