The purpose of this study was to review occupational reproductive abnormalities and occupational bladder cancer in Korea and to discuss their toxicological implications. Reproductive dysfunction as a result of 2-bromopropane poisoning was first reported in Korean workers. In 1995, 23 of the 33 workers (25 female and 8 male workers) who were exposed to 2-bromopropane during the assembly of tactile switch parts developed reproductive and/or hematopoietic disorders. A total of 17 (68%) workers were diagnosed with ovarian failure. Two of the eight male workers experienced azoospermia and four workers experienced some degree of oligospermia or reduced sperm motility. In summary, 2-bromopropane poisoning caused severe reproductive effects in Korean workers. The prognosis was poor for reproductive dysfunction. A few cases of occupational bladder cancer have been reported in Korea, whereas other cancers of the urinary tract have not been reported after occupational exposure. A few cases of benzidine-induced cancer have been reported in Korea and 592 workers in Japan have received compensation for benzidine and beta-naphthylamine-induced cancer. In conclusion, a few cases of benzidine-induced occupational bladder cancer have been reported in Korea. However, benzidine-induced bladder cancer will likely be an important occupational health issue in Korea in the coming years.
2-Naphthylamine/toxicity ; Azoospermia/chemically induced/epidemiology ; Benzidines/toxicity ; Female ; Humans ; Hydrocarbons, Brominated/toxicity ; Infertility/*chemically induced/*epidemiology ; Male ; Occupational Diseases/*chemically induced/*epidemiology ; Occupational Exposure/adverse effects ; Oligospermia/chemically induced/epidemiology ; Primary Ovarian Insufficiency/chemically induced/epidemiology ; Republic of Korea ; Sperm Motility/drug effects ; Urinary Bladder Neoplasms/*chemically induced/*epidemiology

OBJECTIVETo evaluate the effect of the levels of IGF-I in the epididymis and the expression of IGF-I in the testis of adult male rat after the administration of cyclophosphamide.

METHODSNinety-six male adult rats (8 weeks age) were divided into 6 groups. The doses given to the rats of the groups 1 to 5 were 10, 20, 40, 80 and 100 mg/(kg x d), respectively. The remaining group was served as control. All those rats were sacrificed and IGF-I were quantitatively determined by ELISA techniques 2 and 4 weeks after the administration of the drug (by gastric fudge). Immunohistochemical SP technique was used to examine expression of IGF-I in rat testis.

RESULTSThe levels of cell factors (IGF-I) in the epididymis of the rats were gradually reduced with the increasing time and dose after administration of the drug. In the mean time the expression of IGF-I in the tissues of the testis of those rats were also gradually reduced.

CONCLUSIONIn the time of oligozoospermia/azoospermia induced by the administration of cyclophosphamide, the expression levels of IGF-I in the genetic system were significantly reduced. The possible mechanism of these changes could be attributed to the lower spermatogenesis function of the testis caused by the administration of cyclophosphamide.

Animals ; Azoospermia ; chemically induced ; metabolism ; Cyclophosphamide ; toxicity ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Epididymis ; metabolism ; Immunohistochemistry ; Insulin-Like Growth Factor I ; biosynthesis ; Male ; Oligospermia ; chemically induced ; metabolism ; Rats ; Rats, Sprague-Dawley ; Testis ; metabolism

An ideal animal model of azoospermia would be a powerful tool for the evaluation of spermatogonial stem cell (SSC) transplantation. Busulfan has been commonly used to develop such a model, but 30%-87% of mice die when administered an intraperitoneal injection of 40 mg kg^-1. In the present study, hematoxylin and eosin staining, Western blot, immunofluorescence, and quantitative real-time polymerase chain reaction were used to test the effects of busulfan exposure in a mouse model that received two intraperitoneal injections of busulfan at a 3-h interval at different doses (20, 30, and 40 mg kg^-1) on day 36 or a dose of 40 mg kg^-1 at different time points (0, 9, 18, 27, 36, and 63 days). The survival rate of the mice was 100%. When the mice were treated with 40 mg kg^-1 busulfan, dramatic SSC depletion occurred 18 days later and all of the germ cells were cleared by day 36. In addition, the gene expressions of glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor 2 (FGF2), chemokine (C-X-C Motif) ligand 12 (CXCL12), and colony-stimulating factor 1 (CSF1) were moderately increased by day 36. A 63-day, long-term observation showed the rare restoration of endogenous germ cells in the testes, suggesting that the potential period for SSC transplantation was between day 36 and day 63. Our results demonstrate that the administration of two intraperitoneal injections of busulfan (40 mg kg^-1 in total) at a 3-h interval to mice provided a nonlethal and efficient method for recipient preparation in SSC transplantation and could improve treatments for infertility and the understanding of chemotherapy-induced gonadotoxicity.
Adult Germline Stem Cells/transplantation* ; Animals ; Azoospermia/chemically induced* ; Busulfan/toxicity* ; Disease Models, Animal ; Infertility, Male/chemically induced* ; Injections, Intraperitoneal ; Male ; Mice ; Spermatogenesis/drug effects* ; Spermatogonia/drug effects* ; Stem Cell Transplantation/methods*

PURPOSE: Androgen replacement therapy has been shown to be safe and effective for most patients with testosterone deficiency. Male partners of infertile couples often report significantly poorer sexual activity and complain androgen deficiency symptoms. We report herein an adverse effect on fertility caused by misusage of androgen replacement therapy in infertile men with hypogonadal symptoms. MATERIALS AND METHODS: The study population consisted of 8 male patients referred from a local clinic for azoospermia or severe oligozoospermia between January 2008 and July 2011. After detailed evaluation at our andrology clinic, all patients were diagnosed with iatrogenic hypogonadism associated with external androgen replacement. We evaluated changes in semen parameters and serum hormone level, and fertility status. RESULTS: All patients had received multiple testosterone undecanoate (NebidoR) injections at local clinic due to androgen deficiency symptoms combined with lower serum testosterone level. The median duration of androgen replacement therapy prior to the development of azoospermia was 8 months (range: 4-12 months). After withdrawal of androgen therapy, sperm concentration and serum follicle-stimulating hormone level returned to normal range at a median 8.5 months (range: 7-10 months). CONCLUSION: Misusage of external androgen replacement therapy in infertile men with poor sexual function can cause temporary spermatogenic dysfunction, thus aggravating infertility.
Adult ; Androgens/administration & dosage/adverse effects/*therapeutic use ; Azoospermia/*drug therapy ; Erectile Dysfunction/drug therapy ; Humans ; Hypogonadism/*drug therapy ; Infertility, Male/*chemically induced/drug therapy ; Male ; Oligospermia/*drug therapy ; Testosterone/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use

OBJECTIVETo study the ability of bone marrow mesenchymal stem cells (BMSCs) to repair the internal environment of the testis in male azoospermia rats.

METHODSWe established azoospermia models in 22 six-week-old male SD rats by intraperitoneal injection of busulfan at 20 mg per kg body weight. We transplanted allogeneic rat BMSCs (rBMSCs) into the testicular seminiferous tubules of the model rats and, 30 days after transplantation, observed the composition and structure of the seminiferous tubular cells by HE staining and detected the expressions of CD44, CD106, and c-kit in the rBMSCs by immunohistochemistry.

RESULTSThe number of epididymal sperm was significantly reduced in the model rats as compared with the normal controls (P < 0.01). CD44 and CD106, but not c-kit, were expressed in the isolated rBMSCs. At 30 days after transplantation of rBMSCs, lots of new cells were observed in the seminiferous tubules, some expressing CD106 and some expressing the germ cell surface marker c-kit.

CONCLUSIONBMSCs can transdifferentiate into germ cells and repair the damaged seminiferous tubules of sterile rats.

Animals ; Azoospermia ; chemically induced ; therapy ; Biomarkers ; metabolism ; Bone Marrow Cells ; Busulfan ; Cell Membrane ; metabolism ; Epididymis ; Hyaluronan Receptors ; metabolism ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; metabolism ; Proto-Oncogene Proteins c-kit ; metabolism ; Rats ; Rats, Sprague-Dawley ; Seminiferous Tubules ; anatomy & histology ; metabolism ; Spermatozoa ; Staining and Labeling ; Vascular Cell Adhesion Molecule-1 ; metabolism

AIMTo analyze factors influencing the efficacy of hormonal suppression of spermatogenesis for male contraception.

METHODSA nested case-control study was conducted, involving 43 subjects, who did not achieve azoospermia or severe oligozoospermia when given monthly injections of 500 mg testosterone undecanoate (TU), defined as partial suppressors compared with 855 subjects who had suppressed spermatogenesis (complete suppressors). Sperm density, serum testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations at the baseline and the suppression phase were compared between partial and complete suppressors. Polymorphisms of androgen receptor (AR) and three single nucleotide variants and their haplotypes of FSH receptor (FSHR) genes determined by polymerase chain reaction (PCR) and DNA sequencing technique were compared between 29 partial and 34 complete suppressors.

RESULTSBaseline serum LH level was higher and serum LH as well as FSH level during the suppression phase was less suppressed in partial suppressors. Additionally, in a logistic regression analysis larger testis volume, higher serum FSH concentrations alone, or interaction of serum LH, FSH, testosterone and sperm concentrations were associated with degree of suppression. The distribution of polymorphisms of AR or FSH receptor genes did not differ between partial and complete suppressors. In cases with incomplete FSH suppression (FSH 0.2 IU/L), the chances of reaching azoospermia were 1.5 times higher in the subjects with more than 22 CAG triplet repeats.

CONCLUSIONPartial suppression of spermatogenesis induced by 500 mg TU monthly injections is weakly influenced by hormonal and clinical features but not polymorphism in AR and FSHR genes.

Adult ; Azoospermia ; chemically induced ; genetics ; Case-Control Studies ; Contraceptive Agents, Male ; administration & dosage ; Drug Resistance ; genetics ; Follicle Stimulating Hormone ; blood ; Haplotypes ; Humans ; Luteinizing Hormone ; blood ; Male ; Polymorphism, Single Nucleotide ; Predictive Value of Tests ; Promoter Regions, Genetic ; genetics ; Receptors, Androgen ; genetics ; Receptors, FSH ; genetics ; Sperm Count ; Spermatogenesis ; drug effects ; genetics ; Testosterone ; administration & dosage ; analogs & derivatives ; blood ; Trinucleotide Repeats