• 약학회지
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• 제53권5호
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• pp.250-258
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• 2009

Male reproductive function seems to have deteriorated considerably in the past 4 to 5 decades. It was observed a significant decline in mean sperm counts from $113{\times}10^6/ml$ in 1940 to $66{\times}10^6/ml$ in 1990; a fall of $0.94{\times}10^6/ml/year$. We reported that Yacon tuber extracts have spermatogenic effects in rat. In the present study, we tested the spermatogenic effect of Yacon tuber extracts in healthy male volunteers. Subjects were assigned randomly to the control group and the Yacon ethanol extracts administered group (each 12 subjects). And, placebo or Yacon tuber extracts (100 ml) were administered two times daily, by oral for 3 months. Sperm numbers, biochemical parameters and hormone levels were recorded before starting administration, then every month. The Yacon tuber extracts administered group showed significant time dependant increases in according to administration period. Especially, the numbers of sperm increased by 54% after 3 months of administration. And, in Yacon tuber extracts administered group, testosterone and estradiol level were significantly higher than placebo group. On the other hands, Yacon tuber extracts didn't show any toxicity in glucose and lipid metabolism and liver and kidney function. The results of the present study suggest that Yacon tuber extract is a possible therapeutic for the treatment of sperm deficiency.

• 대한수의학회지
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• 제50권2호
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• pp.93-103
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• 2010

This study investigated the potential effects of amitraz on the pre- and postnatal development, behavior, and reproductive performance of offspring of parent rats given amitraz during pre-mating, gestation, and lactation. The test chemical was administered via the drinking water containing 0, 40, 120, and 360 ppm to male rats from 2 weeks before mating to the end of 14-day mating period and to females from 2 weeks before mating, throughout mating, gestation and lactation up to weaning. Based on fluid consumption, the male rats received an average of $0,\;5.7{\pm}1.33,\;13.2{\pm}2.08,$ and $35.8{\pm}3.42$ mg/kg/day amitraz, and the female rats received an average of $0,8.7{\pm}4.42,\;20.1{\pm}9.60,\;and\;47.6{\pm}22.38$ mg/kg/day amitraz, respectively. At 360 ppm, an increase in the incidence of abnormal clinical signs, a suppression in the body weight gain, a decrease in the food consumption and litter size, an increase in the post-implantation loss, and a decrease in the seminal vesicle weight were observed in the parent animals. In addition, a suppression in the body weight gain, a decrease in the grip strength, a delay in the negative geotaxis, an increase in the pre- and post-implantation loss, and a decrease in the number of live embryos were observed in the offspring. At 120 ppm, suppressed body weight gain and reduced food consumption were observed in the parent rats. Suppressed body weight gain and decreased grip strength were also observed in the offspring. There were no signs of either reproductive or developmental toxicity at 40 ppm. Under these experimental conditions, the no-observed-adverse-effect level of amitraz for parent rats and their offspring was estimated to be 40 ppm in rats.

• 한국수정란이식학회지
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• 제25권4호
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• pp.207-213
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• 2010

Thousands of new chemicals have been introduced to environment during last decades. Many of them and common consumer products have been shown to be the endocrine disrupting chemicals. One such chemical group is the phthalates, used in soft poly vinyl chloride (PVC) material and in a huge number of consumer products. The prevalence of these modem chemicals have a remarkable increase. Approximately 3.5 million tons of the main phthalate, di-(2-ethylhexyl) phthalate (DEHP), are produced annually worldwide and indeed, DEHP is considered a ubiquitous environmental contaminant. It has been demonstrated that high doses of phthalate can adversely affect adult and developing animals. In this review, we critically discuss the conclusions of recently original research papers and provide an overview of studies on reproductive disrupting effects of phthalates. In addition, we review the reproductive toxicity data of phthalates in some in vitro research and in both male and female reproductive systems in experimental and domestic animals. Finally, we point out some critical issues that should be addressed in order to clarify the implication of phthalates for human reproduction.

• Toxicological Research
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• 제19권2호
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• pp.123-131
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• 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.

• 대한수의학회지
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• 제40권2호
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• pp.361-371
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• 2000

최근 2-bromopropane(2-BP)이 사람과 실험동물에서 정소독성을 유발한다고 보고된 바 있다. 그러나 수컷 생식기계에 있어서 2-BP의 지연효과에 대해서는 세부적으로 조사된 바가 없다. 본 연구는 Sprague-Dawley 랫드에서 2-BP의 정소독성과 정자발생의 회복을 조사하기 위하여 수행하였다. 5주령의 수컷 랫드에게 2-BP를 1,000mg/kg 용량으로 4주간 반복투여하였고, 투여시작후 1, 2, 3, 4 및 12주째에 부검하였다. 정소독성의 평가는 병리조직학적인 질적평가와 생식기관 중량, 정자두부수 및 재생지수 등의 양적평가로 수행하였다. 시험결과 2-BP를 투여한 랫드에서는 체중과 정소 및 정소상체 중량이 대조군에 비해 시간의존적인 방식으로 억제 또는 감소하였다. 병리조직검사에서는 투여 1주째에 stage I~IV에서 정조세포와 stage VII~IX에서 세사전기 및 세사기의 정모세포가 현저하게 소실되었다. 정조세포는 투여 2주째에 모든 stage에서 광범위하게 소실되었으며, 정자발생주기가 진행됨에 따라 2, 3 및 4주째에는 접합기 정모세포, 비후기 정모세포 및 원형 정자세포가 전구세포의 결손에 의해 점진적으로 소실되었다. 지지세포의 기능적 이상을 암시하는 지지세포의 공포화와 정자세포 저류는 상기한 모든 시기에서 관찰되었다. 8주 회복후인 12주째에는 대부분의 곡세정관이 심하게 위축되어 지지세포만 관찰되었으며, 간질조직에서는 간질세포의 과형성이 인정되었다. 또한 2-BP에 의해 유발된 정소의 손상이 비가역적임을 암시해주는 정자두부와 재생지수의 현저한 감소가 관찰되었다. 상기결과는 랫드의 2-BP를 1,000mg/kg의 용량으로 4주간 반복투여하면 정조세포의 결손에 의해 점진적으로 생식세포가 감소하고 이로 인하여 장기적인 정소위축이 유발된다는 것을 암시해준다.

• 대한한방내과학회지
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• 제27권1호
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• pp.102-113
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• 2006

Objectives & Methods : To obtain the 50% lethal dose(LD50), approximated lethal dose(ALD) and approximated target organs of 'Mahwangyounpae-tang' for further study into such things as repeated dose toxicity, genotoxicity and reproductive toxicity, single dose toxicity was tested in male SD rats according to KFDA Guideline 1999-61[KFDA, 1999] at dosage levels of 2,000, 1,000, 500, 250 and 125 mg/kg/$10m{\ell}$. In this study, mortalities, clinical signs, body weight changes and body weight gains, gross findings and weight of principal organs were detected during and/or after 14 days of single dosing. Results & Conclusions : After 2 or 3 days of dosing, 1 or 2 animals in 2,000 mg/kg-dosing groups died. Excitation and leaping response were observed as test article-treatment related clinical signs. These abnormal signs were restricted to 2,000 and 1,000 mg/kg-dosing groups and survivors recovered to normal within 3 or 4 days after dosing. Significant decrease in body weight were observed in some periods of observation in 2,000 and 1,000 mg/kg-dosing group, from 1 days after dosing compared to those of vehicle control group. Significantly diminished body weight gains were observed in observation periods in 2,000 and 1,000 mg/kg-dosing group compared to those of vehicle control group. Hypertrophy and hemorrhage of heart and decoloration of kidney were observed as test article-treatment related gross findings. These abnormal findings were restricted to 2,000 and 1,000 mg/kg-dosing groups. A significant increase of absolute and relative heart and kidney weight were demonstrated in 2,000 mg/kg-dosing groups. The value for LD50 found in this study was 2,218.57 mg/kg. ALD in this study was 2,000 mg/kg, and the target organs are considered to be the heart and the kidney.

• 동의생리병리학회지
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• 제20권2호
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• pp.442-448
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• 2006

To obtain the 50% lethal dose (LD50), approximated lethal dose (ALD) and approximated target organs of 'Mahwangyounpae-tang' for further study like repeat dose toxicity, genotoxicity and reproductive toxicity, single dose toxicity was tested in male ICR mouse according to KFDA Guideline 1999-61 [KFDA, 1999] at a dosage level of 2,000, 1,000, 500, 250 and $125\;mg/kg/10m{\ell}$. In this study, mortalities, clinical signs, body weight changes and body weight gains, gross findings and weight of principal organs were detected during and/or after 14 days of single dosing. After 2 or 3 days of dosing, 1 or 2 animals in 2,000 and 1,000 mg/kg-dosing groups were died. Excitation and leaping response were observed as test article-treatment related clinical signs. These abnormal signs were restricted to 2,000 and 1,000 mg/kg-dosing groups and they were recovered to normal within 4 days after dosing in case of survivors. A significant decrease of body weight were observed in some periods of observation in 2,000 and 1,000 mg/kg-dosing group from 1 days after dosing compared to those of vehicle control group. A significant decrease of body weight gains were observed in observation periods in 2,000 and 1,000 mg/kg-dosing group compared to those of vehicle control group. Hypertrophy of heart and decoloration of kidney were observed as test article-treatment related gross findings. These abnormal findings were restricted to 2,000 and 1,000 mg/kg-dosing groups. A significant increase of absolute and relative heart and kidney weight were demonstrated in 2,000 mg/kg-dosing groups. LD50 in this study was detected as 2,242.42 mg/kg. ALD in this study was detected as 1,000 mg/kg and the target organ was considered as the heart and kidney.

• Toxicological Research
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• 제24권2호
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• pp.137-150
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• 2008

Sexually mature male and female rats were orally intubated with the organophosphorus insecticide, Pestban at a daily dosage of 7.45 or 3.72 mg/kg bwt, equivalent to 1/20 and 1/40 $LD_{50}$, respectively. Male rats were exposed for 70 days, while the female rats were exposed for 14 days, premating, during mating and throughout the whole length of gestation and lactation periods till weaning. The results showed depressed acetylcholinesterase(AChE) activity in the brain of parents, fetuses and their placentae in a dose-dependent manner. The fertility was significantly reduced with increasing the dose in both treated groups, with more pronounced suppressive effects in the male treated group. The number of implantation sites and viable fetuses were significantly reduced in pregnant females of both treated groups. However, the number of resorptions, dead fetuses, and pre-and postimplantation losses were significantly increased. The incidence of resorptions was more pronounced in treated female compared to male group and was dose dependant. The behavioral responses as well as fetal survival and viability indices were altered in both treated groups during the lactation period. The incidence of these effects was more pronounced in the treated female group and occurred in a dose-related manner. The recorded morphological, visceral, and skeletal anomalies were significantly increased with increasing the dose in fetuses of both treated groups, with more pronounced effects on fetuses of treated females. In conclusion, the exposure of adult male and female rats to Pestban would cause adverse effects on fertility and reproduction.

• Biomolecules & Therapeutics
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• 제4권4호
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• pp.297-300
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• 1996

LBD-001, a recombinant human interferon $\gamma$ produced by genetically engineered yeast as a host system, was administered intraperitoneally to Sprague-Dawley male rats from premating to mating period at least for 60 days and to female rats from at least for 2 weeks before mating to early gestation period (from day 0 to 7 of gestation) at dose levels of $0.35\times10^6, 0.39\times10^6, and 1.38\times10^6$ I.U./kg/day. In the positive control group, ethynylestradiol ($EE_2$; 40 $\mu\textrm{g}$/kg/day) was subcutaneously administered only to female rats during the early gestation period. Effects of the test agents on reproductive performances of the male or female rats and embryonic development were as followings; (1) No significant changes by the treatment of LBD-001 were observed in general behaviors, body weight, food and water consumption, and necropsy of parent animals. However, significant decreases of body weight, food consumption, and water consumption were observed in ($EE_2$ -treated female rats. (2) Mating performances and fertility of parent animals were not significantly affected by the treatment of LBD-001. In ($EE_2$ -treated females, however, the fertility was completely inhibited. (3) No changes in resorption rate and external abnormality of F1 fetuses were observed by the treatment of LBD-001. The results show that LBD-001 at the dose of $1.38\times10^6$ I.U./kg/day or less does not affect general toxicity and reproductive function of parent animals and embryonic development of F1 fetuses.

• Environmental Analysis Health and Toxicology
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• 제23권1호
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• pp.63-65
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• 2008

The tissue distribution of $TiO_2$, nanopaprticles was investigated in mice after oral administration, and skin treatment. Male mice were treated with the dose of 5 g/kg of $TiO_2$ for three consecutive days and sacrificed at 24 hours after the last administration. As results, the orally administered $TiO_2$ nanoparticels were shown to be distributed in the testis, lung, and brain at 24 hours after the last treatment. Kidney does not seem to be the main target of $TiO_2$ nanoparticle distribution. It means that $TiO_2$ nanoparticles (17 nm) are easily absorbed through entero-gastric system and may cause toxicity in brain, lung, and reproductive organs. The distribution of skin treatment showed the same pattern like oral administration.