• Toxicological Research
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• v.14 no.2
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• pp.193-203
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• 1998

The toxicity of DA-125. a new anthracycline anticancer agent, on the male reproductive system was studied in Sprague-Dawley rats. Forty male rats were rando$m\ell$y assigned to Jour groups with ten rats in each group and given single intraveneous doses of DA-125 at dose levels of 0. 12.5. 25. and 50 mg/kg body weight. On day 56 after treatment the animals were allowed to mate. and their male reproductive Junctions and organs were examined in detail. Copulated females were sacrificed on day 20 of gestation for examination of embryo-fetal development. One out of ten rats in the 50 mg/kg group died on day 12 after treatment. Clinical signs such as emaciation. sedation, anorexia. swelling. dark material around eye. alopecia. and diarrhea were observed in the 25 and/or 50 mg/kg groups. Reduction in the body weight gain. decrease in the absolute weights of testes. epididymis and seminal vesicles. and/or decrease in the number of testicular sperm heads were also found. Although histopathological changes such as atrophy of seminiferous tubules. loss or decrease of spermatogenic cells. exfoliation of spermatogenic cells. vacuolization of Sertoli cells. decrease of sperm. and/or increase of necrotic spermatogenic cells in epididymal ducts were observed. no adverse effects on the motility and morphology of epididymal sperm. copulation index. fertility index. and embryo-fetal development were detected in the 25 and 50 mg/kg groups. There were no evidences of male reproductive toxicity in the 12.5 mg/kg group. These results show that single intravenouse doses of DA-125 produce significant dose-related testicular atrophy. histopathological changes. and oligozoospermia in rats and $LD_{10}$ for DA-125 appears to be 50 mg/kg body weight.

• Toxicological Research
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• v.12 no.1
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• pp.93-99
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• 1996

The effect of KTC-1, a new semisynthetic rifamycin antituberculous drug, on general toxicity, reproductive capability and fetal development was investigated in Sprague-Dawley rats. Male rats were administered KTC-1 with mashed feed from 63 days before mating to the end of mating period, and female rats were given from 14 days before mating to day 7 of gestation at dose levels of 0, 375, 750, and 1,500 ppm. The females were sacrificed on day 21 of gestation for examination of their fetuses. At 1,500 ppm, a reduction in body weight gain and testis atrophy were observed in male rats. Histological examination revealed testicular atrophy, absence or decrease of germinal cells, and vacuolization of Sertoli cells in testis. A reduction in body weight gain, a decrease in food consumption were found in female rats. In addition, decreases in the number of corpora lutea, iraplantations, and the litter size of live fetuses were seen. Mating, fertility, and pregnancy performances were also affected. There were no external abnormalities observed by examination of fetuses. At 750 ppm, a reduction in the body weight gain of male and female rats and decreases in the number of implantations and litter size were found. At 375 ppm, no treatment-related effects were observed. The results suggest that the no-effect dose levels (NOELs) of KTC-1 are 375 ppm for males and females on general toxicity, 750 ppm for males and females on reproductive capability, and 375 ppm for fetuses on embryonic development.

• Korean Journal of Veterinary Research
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• v.40 no.2
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• pp.361-371
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• 2000

It has been recently reported that 2-bromopropane (2-BP) induces male reproductive toxicity in both human and experimental animals. However, delayed effects of 2-BP on male reproductive system have not been investigated in detail. The present study was conducted to investigate the testicular toxicity of 2-BP and to determine the recovery of normal spermatogenesis in Sprague-Dawley rats. Male rats aged 5 weeks were administered 1,000mg/kg 2-BP by gavage daily for 4 weeks and sacrificed sequentially at 1, 2, 3, 4 and 12 weeks after initiation of 2-BP treatment. Testicular toxicity was evaluated qualitatively by histopathological examinations and quantitatively by reproductive organ weights, spermatid head count, and repopulation index. In the 2-BP treated rats, the body weights was significantly suppressed and the weights of testes and epididymides were also decreased in a time-dependent manner. On histopathological examination, spermatogonia in stages I-VI and preleptotene and leptotene spermatocytes in stages VII-IX were strongly depleted at 1 week of dosing. Spermatogonia were depleted extensively in all spermatogenic stages at 2 weeks. Continuing with the evolution of spermatogenic cycle, zygotene spermatocytes, pachytene spermatocytes, and round spermatids were sequentially depleted at 2, 3, and 4 weeks of dosing due to the depletion of their precursor cells. Vacuolization of Sertoli cells and spermatid retention were also observed at all time points, suggesting that 2-BP induced Sertoli cell dysfunction. At 12 weeks, after 8 weeks recovery, most of the tubules appeared severely atrophic and were lined by Sertoli cells only. Leydig cell hyperplasia in the interstitial tissue was also found. In addition, dramatic reductions in the number of spermatid heads and repopulation index were observed, indicating that 2-BP-induced testicular injury is irreversible. These results indicate that 4 weeks repeated-dose of 1,000mg/kg 2-BP results in a progressive germ cell loss due to the depletion of spermatogonia followed by long-term testicular atrophy in SD rats.

• Journal of Embryo Transfer
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• v.22 no.2
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• pp.81-87
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• 2007

The purpose of the present study was to determine the preventive effects of the two antioxidant vitamin E and catechin on DEHP-induced disturbance of spermatogenesis in male rats. Rats at 4 weeks of age were randomly allocated into five groups with 20 animals per group. The first group was not any administrated as control. The second group was administrated DEHP (2 g/kg) daily for 14 days. The third group was administrated vitamin E (500 IU/kg) following DEHP treatment by the same method (daily for 14 days). The fourth group was administrated catechin (200 mg/kg) following DEHP treatment by the same method. The fifth group was co-administrated vitamin E (500 IU/kg) and catechin (200 mg/kg) following DEHP treatment by the same method. In order to determine the preventive effects, we examined pathological changes of testis with apoptotic index, and characteristics of sperm with computer assisted sperm analysis (CASA). Vitamin E and catechin supplementation were significantly prevented the testicular atrophy, apoptosis of germ cells in the seminiferous tubules and abnormal rate of sperm. Moreover, sperm concentration, viability and motility was significantly recovered in groups of alone and along with vitamin E and catechin. The results suggest that preventive effects of alone and along administration of vitamin E and catechin on DEHP-induced testicular atrophy damages have been demonstrated.

• The Journal of the Korea Contents Association
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• v.16 no.11
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• pp.767-775
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• 2016

Mumps is an acute viral disease that affects the entire body, including inflammation of the salivary glands. Mumps is accompanied by unilateral or bilateral parotid gland swelling and pain. Mumps virus is spread to others by air, saliva, direct contact, and urine, and occurs in high-density population places such as schools, army, etc. Bilateral testicular involvement is seen in 10-60% of cases. If mumps orchitis affect post-pubertal men, approximately 50% of the infected people are said to experience severe testicular atrophy within 1-2 months as a complication. Mumps orchitis can alter the count, morphology, and motility of sperm and result in oligozoospermia and infertility caused by a rare azoospermia. When suspected of mumps orchitis, active initial symptomatic treatment can prevent infertility due to azoospermia in future adults. A case of mumps orchitis report two cases with references to the ultrasonnography and semen.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.300-311
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• 1998

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), one of the most notorious toxic environmental pollutants, induces various toxic effects in many organs including testes and is regarded as an endocrine disruptor. Korean ginseng, on the other hand, has been well known for its preventive effects on lox- ins, diabetes melltus and hyperlipidemia. We investigated, histopathologically, the effect of Korean Red ginseng water extract (KR-WE) on guinea pig testes damaged by TCDD. Ninety guinea pigs were divided into 6 groups: normal control (NC) group received vehicle and saline; TCDD,1191kg b.w., was administered intraperitoneally to the single dose TCDD-treated (77) group; 100 mghg b.w.16 and 200mg1kg b.w./d KR-WE were injected intraperitoneally to the preventive groups (PIOO and P2OO, respectively) for 28 days from 1 week before TCDD injection, and to the therapeutic groups (CIOO and C2OO, respectively) for 14 days since 1 week after TCDD administration. Increment of body weight was retarded to a larger extent by TCDD. Moreover, body weight of the 77 group decreased significantly 7 days after TCDD exposure, while that of preventive groups kept increasing. Decrease in body weight was not observed in KR-WE-treated groups. Weight decrease in testes caused by TCDD was remarkably protected by KR-WE. Testicles in 77 group displayed decreased tubular size and maturation arrest at the primary or secondary spermatocyte stage. On the other hand, maturation arrest in germ cells by TCDD was improved in KR-WE treated groups. Almost complete protection of the testes was observed in PIOO and P2OO groups. In addition, the therapeutic effect was noticed in C 100 and C2OO groups. These results provided strong evidence that Korean Red ginseng might be a useful agent for the prevention and treatment of testicular damage induced by environmental pollutants.

• Journal of Genetic Medicine
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• v.2 no.1
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• pp.11-15
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• 1998

This paper reports 3 cases with 46,XX sex reversed male. Three 46,XX hypogonadal subjects showed complete sex reversal and had normal phallus and azoospermia. We studied them under clinical, cytogenetic and molecular aspects to find out the origin of the sex reversal. Patients had markedly elevated serum follicle-stimulating hormone (FSH) and lutenizing hormone (LH) and decreased or normal range of serum testosterone. The testicular volumes were small (3-8ml). Testicular biopsy showed Leydig cell hyperplasia and atrophy of seminiferous tubules. We obtained the results of normal 46,XX, and the presence of Y chromosome mosaicism was ruled out through XY dual fluorescent in situ hybridization (FISH). By using polymerase chain reaction (PCR), we amplified short arm (SRY, PABY, ZFY and DYS14), centromere (DYZ3), and heterochromatin (DYZ1) region of the Y chromosome. PCR amplification of DNA from these patients showed the presence of the sex-determining region of the Y chromosome (SRY) but didn't show the centromere and heterochromatin region sequence. The SRY gene was detected in all the three patients. Amplification patterns of the other regions were different in these patients; one had four amplified loci (PABY+, SRY+, ZFY+, DYS14+), another had two loci (SRY+, ZFY+) and the other had two loci (PABY+, SRY+). We have found that each patient's translocation elements had different breakpoints at upstream and downstream of the SRY gene region. We conclude that the testicular development in 46,XX male patients were due to insertion or translocation of SRY gene into X chromosome or autosomes.

• Toxicological Research
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• v.18 no.4
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• pp.375-384
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• 2002

Repeated-dose toxicity of hyrubicin ID6105, a novel anthrarycline anticancer agent, was investigated in Sprague-Dawley rats. ID6105 was injected intravenously to rats at dose levels of 0.04, 0.2 or 1.0 mg/kg/day for 4 week. As a result, there were no dose-related mortality and specific clinical signs of all animals treated with the drug. However body weight gain of both male and female rats treated with a high dose (l.0 mg/kg/day) of ID6105 significantly decreased compared to control. Interestingly, the numbers of RBC and platelets, and concentration of hemoglobin remarkably increased, while protein synthesis was suppressed, which may be related to the atrophy of spleen, thymus and liver. Moreover there were severe lymphocytic depletion in spleen and thymus as well as decrease in the number of hematopoietic cells in bone marrow. Also, degeneration of cardiac muscles and testicular germinal epithelia were observed. Taken together, it is suggested that Long-term administration of ID6105 at high doses over 0.2 mg/kg/day might cause hematopoietic and male reproductive system injuries, in addition to hepatic dysfunction.

• Korean Journal of Veterinary Pathology
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• v.3 no.1
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• pp.27-33
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• 1999

Phosphamidon(PMD) is orgnophosphate insecticide broadly using in agriculture. In order to study PMD toxicity in the testis, histopathological change and apoptosis were assessed following acute and chronic oral administration in rats and chickens. In acute studies, histopathological changes included necrosis and desquamation of spermatogenic cells, multinucleated giant cells in the lumen of seminiferous tubules, and necrotic cells and the giant cells in the epididymal lumen. Atrophy of seminiferous tubule was seen in the chronic exposure with low doses. The toxic effects of PMD in chronic exposure including clinical signs and histopathological changes were more pronounced in chickens than rats. Apoptosis assessment was performed by TUNEL method and Hoechst staining. TUNEL-positive apoptotic cells were found in spermatocytes of seminiferous tubules, testicular apoptosis was more prominent following acute exposure than control and chronic exposure. Above mentioned result noticed that PMD causes apoptotic death and effects directly the spermatocytogenesis.

• Clinical and Experimental Reproductive Medicine
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• v.40 no.2
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• pp.60-66
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• 2013

Objective: Impairment of spermatogenesis has been identified as an inevitable side effect of cancer treatment. Although estrogen treatment stimulates spermatogenic recovery from the impaired spermatogenesis by suppressing the intra-testicular testosterone (ITT) level, side effects of estrogen are still major impediments to its clinical application in humans. Soybeans are rich in genistein, which is a phytoestrogen that binds to estrogen receptors and has an estrogenic effect. We investigated the effects of genistein administration on ITT levels, testis weight, and recovery of spermatogenesis in rats treated with a chemotherapeutic agent, busulfan. Methods: Busulfan was administered intraperitoneally to rats, and then a GnRH agonist was injected subcutaneously into the back, or genistein was administered orally. Results: The weight of the testes was significantly reduced by the treatment with busulfan. The testis weight was partially restored after busulfan treatment by additional treatment with either the GnRH agonist or genistein. Busulfan also induced atrophy of a high percentage of the seminiferous tubules, but this percentage was decreased by additional treatment with either the GnRH agonist or genistein. Treatment with genistein was effective at suppressing and maintaining ITT levels comparable to that in the GnRH agonist group. Conclusion: Genistein effectively suppressed ITT levels and stimulated the recovery of spermatogenesis in rats treated with a chemotherapeutic drug. This suggests that genistein may be a substitute for estrogens, for helping humans to recover fertility after cancer therapy without the risk of side effects.