ABSTRACT
The stromal antigen 3 (STAG3) gene, encoding a meiosis-specific cohesin component, is a strong candidate for causing male infertility, but little is known about this gene so far. We identified STAG3 in patients with nonobstructive azoospermia (NOA) and normozoospermia in the Korean population. The coding regions and their intron boundaries of STAG3 were identified in 120 Korean men with spermatogenic impairments and 245 normal controls by using direct sequencing and haplotype analysis. A total of 30 sequence variations were identified in this study. Of the total, seven were exonic variants, 18 were intronic variants, one was in the 5'-UTR, and four were in the 3'-UTR. Pathogenic variations that directly caused NOA were not identified. However, two variants, c.3669+35C>G (rs1727130) and +198A>T (rs1052482), showed significant differences in the frequency between the patient and control groups (P = 0.021, odds ratio [OR]: 1.79, 95% confidence interval [CI]: 1.098-2.918) and were tightly linked in the linkage disequilibrium (LD) block. When pmir-rs1052482A was cotransfected with miR-3162-5p, there was a substantial decrease in luciferase activity, compared with pmir-rs1052482T. This result suggests that rs1052482 was located within a binding site of miR-3162-5p in the STAG3 3'-UTR, and the minor allele, the rs1052482T polymorphism, might offset inhibition by miR-3162-5p. We are the first to identify a total of 30 single-nucleotide variations (SNVs) of STAG3 gene in the Korean population. We found that two SNVs (rs1727130 and rs1052482) located in the 3'-UTR region may be associated with the NOA phenotype. Our findings contribute to understanding male infertility with spermatogenic impairment.
Subject(s)
Adult , Humans , Male , Asian People/genetics , Azoospermia/genetics , Case-Control Studies , Cell Cycle Proteins/genetics , Gene Expression Regulation/genetics , Genotype , Haplotypes , MicroRNAs/genetics , Oligospermia/genetics , Polymorphism, Single Nucleotide , RNA, Messenger , Republic of Korea , Spermatogenesis/geneticsABSTRACT
The stromal antigen 3 (STAG3) gene, encoding a meiosis-specific cohesin component, is a strong candidate for causing male infertility, but little is known about this gene so far. We identified STAG3 in patients with nonobstructive azoospermia (NOA) and normozoospermia in the Korean population. The coding regions and their intron boundaries of STAG3 were identified in 120 Korean men with spermatogenic impairments and 245 normal controls by using direct sequencing and haplotype analysis. A total of 30 sequence variations were identified in this study. Of the total, seven were exonic variants, 18 were intronic variants, one was in the 5'-UTR, and four were in the 3'-UTR. Pathogenic variations that directly caused NOA were not identified. However, two variants, c.3669+35C>G (rs1727130) and +198A>T (rs1052482), showed significant differences in the frequency between the patient and control groups (P = 0.021, odds ratio [OR]: 1.79, 95% confidence interval [CI]: 1.098-2.918) and were tightly linked in the linkage disequilibrium (LD) block. When pmir-rs1052482A was cotransfected with miR-3162-5p, there was a substantial decrease in luciferase activity, compared with pmir-rs1052482T. This result suggests that rs1052482 was located within a binding site of miR-3162-5p in the STAG3 3'-UTR, and the minor allele, the rs1052482T polymorphism, might offset inhibition by miR-3162-5p. We are the first to identify a total of 30 single-nucleotide variations (SNVs) of STAG3 gene in the Korean population. We found that two SNVs (rs1727130 and rs1052482) located in the 3'-UTR region may be associated with the NOA phenotype. Our findings contribute to understanding male infertility with spermatogenic impairment.
ABSTRACT
Objective To explore the therapeutic effect of phenylethanoid glycosides on cyclophosphamide (CTX)-induced dyszoospermia in mice and to preliminary elucidate the mechanisms involved in the process. Methods Phenylethanoid glycoside was extracted by ethanol extraction.Forty male BALB/C mice were randomly divided into control group,model group,low dose of phenylethanoid glycosides group (50 mg· kg-1 )and high dose of phenylethanoid glycosides group (100 mg·kg-1 ).Except control group,the dyszoospermia mouse model was established by peritoneal injection of CTX at the daily dose of 80 mg· kg-1 ,once daily for successive 5 d. After modeling, phenylethanoid glycosides were intragastrically administered at corresponding doses to each phenylethanoid glycosides group.Equal volume of normal saline was given to the mice in control group and model group by gastrogavage.All the medication was performed once daily for successive 30 d.The testis tissue was obtained 24 h after the last intragastric administration.The level of testosterone in the testis tissue homogenate was determined by enzyme linked immunosorbent assay.The sperm counts, the motility rates, and the teratospermia rates in various groups were compared.The morphological changes of the testis tissue were observed using HE staining.Results Compared with control group, the sperm count and the motility rate were decreased, the teratospermia rate was increased,and the testosterone level in the testis tissue homogenate was decreased in model group(P<0.01).Compared with model group,the sperm counts and the motility rates were increased,the teratospermia rates were decreased, and the testosterore levels in the testis tissue homogenate were increased in phenylethanoid glycosides groups (P<0.05 or P<0.01).The histological results showed atrophy and degeneration of seminiferous tuble,thicker seminiferous epithelium and azoospermic lumina in model group;the number of seminiferous epithelial layers was increased and the seminiferous cells orderly arranged, and many sperms were found in the tubules in phenylethanoid glycosides groups.Conclusion Phenylethanoid glycosides has obviously therapeutical effect on CTX-induced dyszoospermia in mice,and its mechanisms might be correlated with recovering the testosterone level.