• Korean Journal of Microbiology
• /
• v.43 no.3
• /
• pp.151-158
• /
• 2007

The possibility of inadvertent introduction of therapeutic gene expressing viral vectors has raised safety concerns about germ-line infection. Particularly, for indications such as prostate cancer and ovarian cancer, the proximity of the point of viral administration to organs of the reproductive system raises concerns regarding inadvertent germ-line transmission of genes carried by the virus vector. To evaluate the safety of in vivo adenovirus mediated gene transfer, we explored the biodistribution, persistance and potential germ-line transmission of p53-expressing adenovirus (Ad-CMV-p53). Both male and female Balb/c mice were injected with $1{\times}10^9$ PFU of Ad-CMV-p53. The PCR analysis showed that there were detectable vector sequences in liver, kidney, spleen, seminal vesicle, epididymis, prostate, ovary, and uterus. The RT-PCR analysis for detecting inserted gene, p53 showed that Ad-CMV-p53 viral RNA were present in spleen, prostate and ovary. Direct injected male and female mice of adenovirus vector into testis and ovary were mated and their of offspring were evaluated for germ-line transmission of the adenoviral vector. The PCR and RT-PCR analysis showed no evidence of germline transmission, although vector sequences were detected in DNA extracted from gonadal tissues. Real-time PCR result confirmed a significant decrease of adenovirus in gonad tissues 1 week after injection. We have also analysed the cell specific localization of viral DNA in gonad tissues by using in-situ PCR. Positive signals were detected in interstitial tissue but not in seminiferous tubule in sperm. In the case of ovary, adenovirus signal were localized to the stromal tissue, but no follicular signals were observed. Together, these data provide strong evidence that the risk of the Inadvertent germ-line transmission of vector sequences following intraperitoneal or direct injection into genito-urinary system of adenovirus is extremely low.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2002.11b
• /
• pp.149-150
• /
• 2002

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent halogenated aromatic hydrocarbon congener that induces expression of several genes including CYP1A. Exposure to TCDD results in many toxic actions such as carcinogenesis, hepatotoxicity, immune suppression, reproductive toxicity and developmental toxicity.(omitted)

• Toxicological Research
• /
• v.32 no.4
• /
• pp.327-335
• /
• 2016

This study aimed to evaluate the potential toxicity and safety of ethyl hydrogen adipate (EHA) by determining its effect on the reproductive function and development of Sprague-Dawley (SD) rats at dose levels of 0 (control), 200, 400, and 800 mg/kg/day. One male and five females of the 800 mg/kg/day died. Body weight loss was observed in the males of the 800 mg/kg/day and in females of the 400 and 800 mg/kg/day. In addition, mating indices decreased and pre-implantation loss rates increased in parental animals of the 400 and 800 mg/kg/day. The gestation index decreased in the male and female rats of the 800 mg/kg/day. Moreover, the body weight of the pups from the 800 mg/kg/day group decreased on post-parturition day 4. These results indicated that the no-observed-adverse-effect level of EHA for parental males and females was 400 mg/kg/day and 200 mg/kg/day, respectively, and that for pups was 400 mg/kg/day.

• Proceedings of the Korean Society of Embryo Transfer Conference
• /
• 2002.11a
• /
• pp.110-110
• /
• 2002

Rapidly progressive interstitial renal fibrosis has recently been reported in young women who have been on a slimming regimen including chinese herbs. Aristolochic acid, suspected as the causal factor of this renal disease, is a well known carcinogen. It has been known that Madouling (Aristolochiae fructus) contains aristolochic acid. The objective of this study was to investigate the effects of Madouling, Madouling-tang, which are the extract mixture from 10 different chinese herbs including Madouling, and aristolochic acid on reproductive and developmental toxicity. Female rats were administered orally with the extracts of Madouling, madouling-tang, and aristolochic acid from 14 days before mating to day 17 of gestation. Madouling (8mg/kg) decreased fertility in the 8mg/kg group, but Madouling-tang and aristolochic acids did not. Significant decrease of mean fetal body weights were observed in the 16mg/kg group of aristolochic acids. External, visceral and skeletal malformation of fetuses were not observed with treatment. Histopathological examination showed the discrete damage of kidney in the 8mg/kg group of Madouling and 16mg/kg groups of aristolochic acid. In whole embryo culture, Madouling and Madouling-tang caused the retardation of growth and development of embryo in the dose of 1 $\mu$g/ml and 0.02 $\mu\textrm{g}$/kg, respectively while aristolochic acids showed the similar effect in the dose of 300 $\mu\textrm{g}$/kg. These results indicate that Madouling, up to 0.05mg/kg (prescription dose to human) has no adverse effects on the fertility, reproduction and development of Sprague-Dawley rats.

• Toxicological Research
• /
• v.20 no.2
• /
• pp.131-136
• /
• 2004

3-Monochloro-1,2-propanediol(3-MCPD) is a toxic compound, often present in different foods containing acid hydrolyzed(AH) protein, like seasonings and savory food products. The purpose of the present study was to investigate the effects of 3-MCPD on male fertility, sperm and testosterone secretion. In vivo male fertility test was performed for observing the adverse effects of 3-MCPD on the function of male reproductive system and pregnancy outcome. 0.01, 0.05, 0.25, 1 and 5 mg/kg b.w. of 3-MCPD was given daily by gavage to groups of 15 adult male SD rats for 4 weeks. At the end of pre-treatment period, males were mated overnight with normal females. Following morning, males demonstrating successful induction of pregnancy were sacrificed on that day to assess sperm parameters and histopathology of reproductive organs. The resulting pregnant females were sacrificed on day 20 of gestation to evaluate pregnancy outcome. As a result, four-week paternal administration with 3-MCPD resulted in adverse effects on male fertility and pregnancy outcome without remarkable histopathological changes in testes and epididymides; sperm motility, copulation index and fertility index were markedly decreased in the treated group and numbers of live fetuses showed steep dose-response curves. Also, spermatogenesis was investigated in this experiment. However, no effect was observed on production of sperm in testes treated with 3-MCPD for 4 weeks. Hormone assay was performed for observing the effects of 3-MCPD on testosterone and luteinizing hormone (LH) in blood and testes of male SD rats and cultured primary Leydig cell. In result, significant changes of related hormones did not observed by treatment of 3-MCPD. These results indicated that paternal treatment with 3-MCPD induced spermatotoxic effect, which caused an antifertility on male.

• Biomolecules & Therapeutics
• /
• v.6 no.1
• /
• pp.82-88
• /
• 1998

LBO0014, a new recombinant human erythropoietin, was at dose levels of 0, 120, 600, and 3,000 IU/kg/day administered intravenously to pregnant Sprague-Dawley rats during the organogenetic period. All dams were subjected to caesarean section on day 20 of pregnancy, Effects of test substance on dams and embryonic development of Fl fetuses were examined. No treatment-related changes in clinical signs, body weight, and food consumption were observed at all doses tested. At necropsy spleen enlargement was found at 3,000 lU/kg. There was an ulcrease in the spleen weight at 600 and 3,0007/kg. Developmental toxicity was evident as increased resorptions at 3,000 lU/kg. At 600 and 3,000 RJ/kg, retarded ossification of fetuses occurred at an incidence of 31.3% and 64.7%, respectively. In addition, there was a delay in ossification of sternebrae and sacrocaudal vertebrae at 600 and 3,000 lU/kg. A decrease in the number of metacarpi and metatarsi was also seen at 3,000 nJ/kg. The results show that the no observed adverse effect dose level (NOAEL) for material toxicity was over 3,000 IU/kg/day and the NOAEL for developmental toxicity was 120 IU/kg/day.

• Toxicological Research
• /
• v.19 no.2
• /
• pp.123-131
• /
• 2003

This study was carried out to assess the combined repeated dose, reproduction and developmental toxicities of benzoyl peroxide for OECD SIDS (Screening Information Data Set) program. Male and female Sprague-Dawley rats were exposed to benzoyl peroxide at dose levels of 0, 250, 500 and 1,000 mg/kg/day for 29 days for males and for 41-51 days for females. No deaths were found in all animals including control group during exposure period. No hematological effects attributable to benzoyl peroxide were observed in all treated groups. Significant decrease in the weight of testes and epididymis were observed in males at 1,000 mg/kg/day. In females at 1,000 mg/kg/day, slight histopathological effects in uterus such as epithelial vacuolation or hyperplasia were observed. No treatment-related changes in precoital time and rate of copulation, fertility and gestation period were noted in all treated groups. There was no evidence of teratogenic effect of benzoyl peroxide, but body weight of pups at 1,000 mg/kg/day was significantly decreased. NOAEL for combined repeated dose and reproduction/developmental toxicity was 500 mg/kg/day.

• Biomolecules & Therapeutics
• /
• v.6 no.2
• /
• pp.151-158
• /
• 1998

Aspalatone, a new antithrombotic agent, was administered orally to pregnant Sprague-Dawley rats during the organogenetic period at dose levels of 0, 20, 100 and 500 mg/kg/day. All dams were subjected to caesarean section on day 20 of pregnancy. Effects of test substance on dams and embryonic development of F1 fetuses were examined There were treatment-related decreases in body weight and food consumption in the 500 mg/kg group. There was a increase in the spleen weight in the 100 and 500 mg/kg groups. Develo-pmental toxicity was evident as decreased fetal body weights and increased fetal malformations in the 500 mg/ kg group. External and skeletal malformations of fetuses occurred at an incidence of 1 and 8.2%, respectively. In addition, there was a delay in ossification of sternebrae and sacrocaudal vertebrae in the 500 mg/kg group. The results show that the no observed adverse effect dose level (NOAEL) for maternal toxicity was 20 mg/kg/ day and for developmental toxicity was 100 mg/kg/day.

• Clinical and Experimental Reproductive Medicine
• /
• v.50 no.1
• /
• pp.26-33
• /
• 2023

Objective: Human exposure to multiple xenobiotics, over various developmental windows, results in adverse health effects arising from these concomitant exposures. Humans are widely exposed to bisphenol A, and acetaminophen is the most commonly used over-the-counter drug worldwide. Bisphenol A is a well-recognized male reproductive toxicant, and increasing evidence suggests that acetaminophen is also detrimental to the male reproductive system. The recent recognition of male reproductive system dysfunction in conditions of suboptimal reproductive outcomes makes it crucial to investigate the contributions of toxicant exposures to infertility and sub-fertility. We aimed to identify toxicity in the male reproductive system at the mitochondrial level in response to co-exposure to bisphenol A and acetaminophen, and we investigated whether melatonin ameliorated this toxicity. Methods: Male Wistar rats were divided into six groups (n=10 each): a control group and groups that received melatonin, bisphenol A, acetaminophen, bisphenol A and acetaminophen, and bisphenol A and acetaminophen with melatonin treatment. Results: Significantly higher lipid peroxidation was observed in the testicular mitochondria and sperm in the treatment groups than in the control group. Levels of glutathione and the activities of catalase, glutathione peroxidase, glutathione reductase, and manganese superoxide dismutase decreased significantly in response to the toxicant treatments. Likewise, the toxicant treatments significantly decreased the sperm count and motility, while significantly increasing sperm mortality. Melatonin mitigated the adverse effects of bisphenol A and acetaminophen. Conclusion: Co-exposure to bisphenol A and acetaminophen elevated oxidative stress in the testicular mitochondria, and this effect was alleviated by melatonin.

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.294.1-294.1
• /
• 2002

The effects of estradiol and its metabolites on the regulation of CYP1A1 expression. K.E. Joung and Y.Y. Sheen College of Pharmacy, Ewha womans University, Seoul. 120-750, Korea 2, 3.7.8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent halogenated aromatic hydrocarbon congener that induces expression of several genes including CYP1A1. Exposure to TCDD results in many toxic actions such as carcinogenesis, hepatotoxicity. immune suppression. and reproductive and developmental toxicity. (omitted)