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Developmental Toxicity by Exposure to Bisphenol A Diglycidyl Ether during Gestation and Lactation Period in Sprague-dawley Male Rats

  • Hyoung, Un-Jun;Yang, Yun-Jung;Kwon, Su-Kyoung;Yoo, Jae-Hyoung;Myoung, Soon-Chul;Kim, Sae-Chul;Hong, Yeon-Pyo
    • Journal of Preventive Medicine and Public Health
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    • v.40 no.2
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    • pp.155-161
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    • 2007
  • Objectives : Bisphenol A diglycidyl ether (BADGE) is the major component in commercial liquid epoxy resins, which are manufactured by co-reacting bisphenol A with epichlorohydrin. This study was performed to show the developmental effects of prenatal and postnatal exposures to BADGE in male rat offspring. Methods : Mated female rats were divided into four groups, each containing 12 rats. The dosing solutions were prepared by thoroughly mixing BADGE in corn oil at the 0, 375, 1500 and 3000 mg/kg/day concentrations. Mated females were dosed once daily by oral gavage on gestation day (GD) 6 - 20 and postnatal day (PND) 0 - 21. Pregnant female dams were observed general symptoms and body weight. Also, male pups were observed the general symptoms, body weight, developmental parameters (e.g. anogenital distance, pina detachment, incisor eruption, nipple retention, eye opening, testis descent), organ pathologic changes and hormone levels of plasma. Results : Pregnant rats treated with BADGE died at a rate of about 70% in the 1500 mg/kg/day group and all rats treated with 3000 mg/kg/day died. Body weight, for male pups treated with doses of 375 mg/kg/day, was significantly lower than in the control group at PND 42, 56, and 63 (p<0.05). Evaluation of body characteristics including; separation of auricle, eruption of incisor, separation of eyelid, nipple retention, descent of testis, and separation of the prepuce in the BADGE treated group showed no difference in comparisons with the control group. AGD and adjusted AGD (mm/kg) for general developmental items in BADGE 375 mg/kg/day treated pups tended to be longer than in controls, however, these differences were not statistically significant. Relative weights of adrenal gland, lung (p<0.05), brain, epididymis, prostate, and testis (p<0.01) were heavier than in control in measures at PND 9 weeks. There were no significant changes in comparisons of histological findings of these organs. Loss of spermatids was observed in the seminiferous tubule at PND 9 weeks, but no weight changes were observed. The plasma estrogen levels were similar in the control and treatment groups at PND 3, 6 and 9 weeks. The plasma testosterone levels in the control group tended to increase with age. However, in the BADGE 375 mg/kg/day treated male pups it did not tend to increase. Conclusions : These findings suggest that BADGE is a chemical that has developmental effects consistent with it being an endocrine disruptor.

Effect of Dietary Supplementation of DHA and AA on the Incorporation of Long Chain Fatty Acid and DNA Content in the Developing Brain of Rats (쥐에서 뇌발달 과정중에 식이에 첨가한 DHA와 AA가 뇌조직의 지방산조성과 DNA 함량에 미치는 영향)

  • 박현서
    • Journal of Nutrition and Health
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    • v.32 no.5
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    • pp.526-532
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    • 1999
  • The aim of this study was to observe whether the dietary supplementation of docosahexaenoic acid(DHA). In growing rats requires extra supplementation of arachidonic acid(AA) for brain development. Sprague-Dawley rats were divided into three groups, each fed a different diet. In the FO group, dams were fed a DHA-rich FO diet during pregnancy and lactation and pups were fed the same diet until 10 weeks old. In the AO group dams and pups were similarly fed a FO diet after weaning. DHA and AA were most effetively deposited in the developing brain during pregnancy and lactation in rats. However, FO-W pups showed significantly lower level of DHA at 0-3 weeks compared with the FO and AO groups and than slowly increased DHA levels to about 87% of other groups at 10 weeks with the introduction of the FO diet after weaning. The total amount of DNA in whole brain rapidly reached a maximum level at 3 weeks and then was sustained at a constant level after 5 weeks of age. The DNA content was positively correlated with DHA level but not with AA level in the developing brain. DNA content was significantly lower in the FO-W group compared to the FO and AO group at 3 weeks of age. However, the DNA content of brain in FO-W pups increased to 80% of the FO group level at 10 weeks after feeding the FO diet after weaning. The relative percentage of AA in brain lipids was significantly reduced in the early stage of brain development when only DHA was supplemented. However, DHA supplementation had no significant effect on the incorporation of AA when the approximately 35% of LA in the FO diet was substituted by preformed AA. These results suggest that large quantities of DHA could interfere with the normal conversion of LA to AA if LA is not supplemented enough together with DHA. Therefore, high DHA supplementation may require preformed AA in the diet even though AA has no significant correlation with the DNA content in brain. DHA supplementation after weaning also improved the incorporation of DHA into brain and content of DNA even though brain development was almost completed, suggesting that a low level of DHA supplementation without AA addition might be necessary to improve brain development during infancy as well as during pregnancy and lactation.

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Production of Identical Multiplets from Deep-Frozen Embryos (동결보존배를 이용한 일란성 다태생산에 관한 연구)

  • Shin Sang-Tae
    • Journal of Veterinary Clinics
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    • v.10 no.2
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    • pp.243-249
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    • 1993
  • Although plenty of experiments for production of genetically identical twins have been reported, most of these reports were focused on microsurgical bisection of morula stage embryos, and little research has been performed for the production with frozen emb교os. The objective of these experiments were to assess the in vitro and in vitro developmental potential of blastomeres isolated from frozen-thawed 4-cell and 8-cell mouse embryos and to produce the identical multiplets from those embryos. The percentages of isolated 1/4, 2/4, 4/4, (control), 1/8, 2/8, 3/8, 4/8 and 8/8(control) blastomeres of 4-cell and 8-cell mouse emb교os which developed to normal blastocyst were 38.7%, 73.6%, 96.2(control), 15.1%, 40.1%, 65.9%, 88.3%, and 98.5%(control), respectively. The percentages of isolated 1/4, 2/4, 4/4(control), 1/8, 2/8, 3/8, 4/8 and 8/8(control) blastomeres of frozen-thawed 4-cell and 8-cell mouse embryos which developed to normal blastocyst were 35.6%, 68.5%, 100.0%(control), 16.1%, 50.6%, 71.7%, 90.9% and 100.0%(control), respectively. Normal 26 pups were obtained by transfer of 240 blastocyts developed 1, on 1/4 to 8/8 blastomeres. Those 26 pups obtained, 4 identical twins were produced from 2/4, 2/8, 3/8 and 4/8 blastomeres.

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Reproductive and Developmental Toxicity Screening Test of Ethyl Hydrogen Adipate in Rats

  • Nam, Chunja;Hwang, Jae-Sik;Han, Kyoung-Goo;Jo, Eunhye;Yoo, Sun-kyoung;Eom, Ig-Chun;Kang, Jong-Koo
    • Toxicological Research
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    • v.32 no.4
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    • pp.327-335
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    • 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.

Effect of Suckling on Progesterone Secretion during Lactation in the Rat (포유중인 Rat 의 Progesterone 분비에 대한 포유 효과)

  • 오석두;성환후;민관식;윤창현
    • Korean Journal of Animal Reproduction
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    • v.23 no.2
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    • pp.95-103
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    • 1999
  • This experiment was conducted to investigate how the lactation regulation such as restricted-lactation and early weaning during the suckling period influences on ovarian functions and change in serum levels of progesterone in primiparous rats. All the rats were raised in the individual cage from a few days before parturition through the suckling period. The normal lactation(NL) groups were controled 8 pups. The restricted-lactation(RL) and weaned(W) groups were subdivided into 5 subgroups as RL0, RL5, RL10, RL15 and RL20 as well as W0, W5, W10, W15, and W20 according to the day of onset of suckling. The number of pups were regulated from 8 to 4 on experimental strating day in RL gropus, and also perfectly weaned on the each on-set day in W groups. The results obtained were summarized as follows: 1. During the whole suckling period of 25 days the pups in RL group grew significantly(P<005) faster than those in normal-lactation(NL) group. The pups in earlier RL group grew significantly(P<0.05) faster than those in later RL rats, and there was no found any significant difference in body weight of pups between RL20 and NL group. The gestation period and litter size were found to be 21.53$\pm$0.04 days and 13.75$\pm$0.07, respectively. 2. The estrous cycle was not expressed in the NL group through the whole suckling period. An irregular estrous cycle was found around day 20 in RL0 group, and the regular estrous cycles were exhibited continuously from day 10 in the day 0 weaned rats. 3. In the rats of NL group the serum progesterone concentration increased from 33.16$\pm$2.64ng/$m\ell$ on day 0 to 122.5$\pm$53.68 ng/$m\ell$ on day 10, and then decreased slightly to 97.30$\pm$3.21 ng/$m\ell$ on day 20, but then decreased abruptly. However, the serum level of progesterone decreased greatly(P<0.05) in 5 to 10 days following suckling restriction in the rats from which suckling began to be under restriction on day 0 or day 15. In the early weaning group the significant ( (P<0.05) decrease in progesterone concentration was found similarly in 48 hours following weaning in all the rats weaned on day 0 through day 20. It was suggested that lactation stimulation is a very pivotal on the function of ovary.

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The Effects of Mortierella alpina Fungi and Extracted Oil (Arachidonic Acid Rich) on Growth and Learning Ability in Dam and Pups of Rat (흰쥐의 Mortierella alpina 균사체와 추출유의 섭취에 의한 생육 효과와 학습능력 비교)

  • 이승교;강희윤;박영주
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.31 no.6
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    • pp.1084-1091
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    • 2002
  • Mortierella alpina, a common soil fungus, is the most efficient organism for production of production acid presently known. Since arachidonic acid are important in human brain and retina development, it was undertaken the growing effect containing diet as a food ingredient. Arachidonic acid rich oil derived from Mortierella alpina, was subjected to a program of studies to establish for use in diet supplement. This study was compared the growth and learning effect of fungal oil rich in arachidonic acid by incorporated into diets ad libitum. Sprague-Dawley rats received experimental diets 5 groups (standard AIN 93 based control with beef tallow, extract oil 8%, and 4%, and Mortierella alpina in diet 10% and 20%) over all experiment duration (pre-mating, mating, gestation, lactation, and after weaning 4 weeks). Pups born during this period consumed same diets after wean for 4 weeks. There was no statistical significance of diet effects in reproductive performance and fertility from birth to weaning. But the groups of Mortierella alpine diet were lower of weight gain and diet intake after weaning. The serum lipids were significantly different with diet groups, higher TG in LO (oil 4%) group of dams, and higher total cholesterol in LF (M. alpina 10%) of pups, although serum albumin content was not significantly different in diet group. The spent-time and memory effect within 4 weeks of T-Morris water maze pass test in dam and 7-week- age pups did not differ in diet groups. On the count of backing error in weaning period of pups was lower in HO(extracted oil 8%) group. In the group of 10% and 20% Mortierella alpina diet, DNA content was lower in brain with lower body weight, but liver DNA relative to body weight was higher than control. Further correlation analyses would be needed DNA and arachidonic acid intakes, with Mortierella alpina diet digestion rate.

A Study on the Transmission of a Transgene in the Offspring of Transgenic Mice (형질전환 생쥐의 후손에서 외래 유전자의 유전성에 대한 연구)

  • 염행철
    • Korean Journal of Animal Reproduction
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    • v.20 no.4
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    • pp.453-458
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    • 1997
  • It is known that the incorporation of genes into transgenic mice is generally stable and is p passed on to succeeding generations in a Mendelian fashion. In this report, transgenic mice were set as a model to evaluate whether the transgenes are transmitted in a Mendelian principle in a successive generations and how they are tran s smitted into their offspring. A 3.0 kb linear DNA fragment, containing the MMTV LTR, bovine aSI casein cDNA and SV 40 splicing and polyadenylation site; was microinjected into fertilized mouse embryos. The tail DNAs of the resulting pups were subjected to dot and Southern hybridizations to screen transgenic founders. The DNAs of their offspring were anlyzed by PCR to confirm the transmission of the transgene from F0. Out of 72 live pups four pups (5.6%), 3 males and 1 female, were positive for the transgene. The rates of transmission from F0 into F1 were 33.3, 7.7, 0, and 62.5%. Those from F1 into F2 were 63.6, 5.9, and 68.8% and those from F2 into F3 were 85.7, and 88.2%. In this report, the transmission pattern of transgenes in transgenic mice into their offspring was demonstrated. It either follows or does not follow in a Mendelian fashion. Deletion or loss of the transgenes from F0 in some lines became apparant to the succeeding generations.

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Effect of Suckling on Serum Insulin-like Growth Factor- I Levels in the Primiparous Rat (Rat 의 포유조절이 혈중 Insulin-like Growth Factor- I 수준에 미치는 영향)

  • 오석두;성환후;민관식;윤창현
    • Korean Journal of Animal Reproduction
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    • v.24 no.1
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    • pp.35-40
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    • 2000
  • This experiment was conducted to investigate how restricted-lactation and regulation of weaning-time influence the levels of insulin-like growth factor-I (IGF-I) in primiparous rats during the suckling period. All the rats were raised in the individual cage from a few days before parturition through the whole suckling period. The restrictedlactation (RL) and weaned (W) groups were subdivided into 5 subgroups as RL0, RL5, RL10, RL15 and RL20 as well as W0, W5, Wl0, W15, and W20 according to the day of onset of suckling only 4 pups in restriction lactation and of suckling no pups in weaned group, respectively, in contrast to suckling 8 pups per litter in normal lactation (NL) group. The results obtained were summarized as follows: 1. The serum IGF- I concentration of NL rats was 750.59$\pm$3.52ng/$m\ell$ on Day 0, which was not changed until Day 15, and then it was increased through the subsequent suckling period to 1690.20$\pm$4.42ng/$m\ell$ on Day 25. 2. The IGF-I concentrations of early restricted lactation (RL0, RL5) were 1395.90$\pm$3.45ng/$m\ell$ and 1351$\pm$3.23ng/$m\ell$ on Day 10, respeotively. It was significantly higher (P<0.05) than NL group (745.96$\pm$2.24ng/$m\ell$), and then was not different between group from day 15 of lactation. 3. The IGF- I concentration of W-group in the early lactation was higher (P<0.05) than NL group during the first week of lactation. But it was decreased to the similar concentration as NL group on Day 10. These data show that lactation stimulus may regulate the IGF-I concentration.

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Effect of Casein Soy Protein and Corn Gluten as Protein Sources in Diets on the Cellular Development of Rats during the Prenatal and Lactating Periods (식이내 단백질 급원의 종류가 태아기와 수유기동안 흰쥐의 세포 발달에 미치는 영향)

  • Kang, In-Ok;Kim, Sun-Hee
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.13 no.2
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    • pp.156-162
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    • 1984
  • The objective of this study was to investigate the influence of three types of protein source in a basal diet during the prenatal and lactating periods on the cellular growth and development of organs in rate. Twenty four pregnant Sprague-Dawley rats weighing 187.7${\pm}$18.5 g were fed ad libitum diets containing casein, soy protein, or corn gluten. The weight of organ and the contents of DAN, RNA, and protein of organs in pups were determined at 0, 3, 7, 14, and 21 days after the birth. Dietary intake of rats during trimester of pregnancy and lactation were significantly higher in the rats fed case in containing diet than those of rats fed the corn gluten diet. Body weight of the progeny fed casein diet at birth and after 7 days were significantly higher than those of rats fed the corn gluten diet. The weight of brain, liver, and kidney of pups which fed corn gluten diet were significantly lower than those fed the casein diet. DNA contents in the brain of pups fed the casein and the soy protein were slightly higher than those fed the corn gluten diet. RNA and protein contents of the brain, and DNA, RNA and protein contents of the liver of the corn gluten treated group were significantly lower than those of the others.

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Chronic exposure of nicotine modulate the expressions of cerebellar glial glutamate transporters in rats

  • Lim, Dong-Koo
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.287.1-287.1
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    • 2002
  • To study the expressions of glutamate transporter subtypes in cerebellar astrocytes following the chronic exposure of nicotine from mating, rats were treated with nicotine (25 ppm) from the beginning of mating through drinking water. After delivery. each group was divided into two groups. Groups were exposed to either distilled water or nicotine. From 7 day-old pups at each group. cerebellar astrocytes were prepared. Ten days after culture. the expressions of glutamate transporter subtypes (GLAST and GLT-1) were determined using immunochemistry and immunoblot. (omitted)

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