Molecular analysis of the androgen receptor gene in Hong Kong Chinese infertile men.

PURPOSE: To investigate the relationship between CAG repeat length in the androgen receptor gene and impaired spermatogenesis in Hong Kong Chinese population. METHODS: The CAG repeat region was amplified by polymerase chain reaction (PCR) in 85 nonobstructive azoospermic or severe oligozoospermic men, and 45 fertile males. The number of CAG repeat was analyzed by DNA sequencing. Serum FSH, LH, and testosterone levels were also determined in these men. RESULTS: Among nonobstructive azoospermic males, three men (5.7%) possessed short CAG repeats (< 16), and three (5.7%) other men possessed long CAG repeats (> 30). Short CAG repeats (< 16) were also found in two severe oligozoospermic males (6.3%). The incidence of infertile men with short or long CAG repeats is significantly higher in the azoospermic group (p = 0.03) but not in the severe oligozoospermic group (p = 0.17) when compared with the fertile controls CONCLUSION: Our data suggest an association between CAG repeat lengths and impaired spermatogenesis in azoospermic males in our population.

Specific expression of VCY2 in human male germ cells and its involvement in the pathogenesis of male infertility.

Abnormal spermatogenesis in men with Y-chromosome microdeletions suggests that genes important for spermatogenesis have been removed from these individuals. VCY2 is a testis-specific gene that locates in the most frequently deleted azoospermia factor c region in the Y chromosome. We have raised an antiserum to VCY2 and used it to characterize the localization of VCY2 in human testis. Using Western blot analysis, the affinity-purified polyclonal VCY2 antibody gave a single specific band of approximately 14 kDa in size, corresponding to the expected size of VCY2 in all the collected human testicular biopsy specimens with normal spermatogenesis. Immunohistochemical analyses showed that VCY2 localized to the nuclei of spermatogonia, spermatocytes, and round spermatids, except elongated spermatids. At the ultrastructural level, VCY2 expression was found in the nucleus of human ejaculated spermatozoa. To determine the possible relationship of VCY2 with the pathogenesis of male infertility, we examined a group of infertile men with and without Y-chromosome microdeletions and with known testicular pathology using VCY2 antibody. VCY2 was weakly expressed at the spermatogonia and immunonegative in spermatocytes and round spermatids in testicular biopsy specimens with maturation arrest or hypospermatogenesis. The specific localization of the protein in germ cell nuclei indicates that VCY2 is likely to function in male germ cell development. The impaired expression of VCY2 in infertile men suggests its involvement in the pathogenesis of male infertility.

A comparative study of Y chromosome microdeletions in infertile males from two Chinese populations.

PURPOSE: To compare the prevalence and type of Y-microdeletions in Hong Kong and Shanghai men with severe male-factor infertility. METHODS: Seven Y-linked sequence tagged site (STS) primers and seven gene-specific primers were screened in 293 infertile males (139 from Hong Kong and 154 from Shanghai) and 161 fertile men (61 from Hong Kong and 100 from Shanghai). Serum FSH, LH, and testosterone levels were also measured in these men. RESULTS: The incidence of Yq microdeletions in nonobstructive azoospermic men from Hong Kong (8.5%) and Shanghai (6%) was similar. Yq microdeletions were observed in severe oligospermic patients (8.5%) from Hong Kong but not from Shanghai. Among the 9 Hong Kong men with Y-microdeletions, 8 had AZFc deletion and one had AZFb deletion. In contrast, 6 of 9 men from Shanghai with Y-microdeletions had AZFb deletion. The incidence of AZFb deletion among Y-microdeleted men was statistically different between the two populations. Two of the men with AZFb deletion also had AZFa and AZFc deletions. CONCLUSIONS: Regional variations in the type of Y-microdeletion existed between Hong Kong and Shanghai infertile males.

The synthesis and fate of glycodelin in human ovary during folliculogenesis.

The ontogeny of glycodelin in human ovarian follicles during folliculogenesis was studied. Glycodelin immunoreactivity began to be detected in the granulosa cells and thecal cells of late secondary follicles. Immunoreactivity was also found in both the luteinized granulosa cells and cumulus cells obtained from women undergoing the assisted reproduction treatment. However, only the luteinized granulosa cells, and not the cumulus cells, expressed glycodelin mRNA. Results also showed that the cumulus cells took up radiolabelled glycodelin and partially deglycosylated some of it. Glycodelin (and a partially deglycolsylated form of glycoldelin) appeared to complex with two cytoplasmic or membrane components of the cumulus cells. The data also demonstrated that ZIF-1, a glycoprotein isolated from human follicular fluid, was immunologically similar to glycodelin. In conclusion, we suggest that glycodelin is synthesized in the granulosa cells of ovarian follicles at late secondary follicle stage. It then may be released into the follicular fluid from where it is taken up and partially modified by the cumulus cells.