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3 "Pit-1"
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Original Article
Effects of Toluene on the Expression of Placental PRL-GH Family Genes and Reproduction in the Rat
Byong Soo Choe, Chae Kwan Lee, Deog Hwan Moon, Byung Chul Son, Dae Hwan Kim, Chang Hee Lee, Hwi Dong Kim, Jung Won Kim, Jong Eun Kim, Chae Un Lee
Korean Journal of Occupational and Environmental Medicine 2004;16(3):262-275.   Published online September 30, 2004
DOI: https://doi.org/10.35371/kjoem.2004.16.3.262
AbstractAbstract PDF
OBJECTIVES
The purpose of this experimental study was to investigate the toxic effects of toluene on the placental functions and reproductionin the rat. In this study, the expression of placental prolactin-growth hormone (PRL-GH) and Pit-1 genes, the frequency of placental trophoblast cells, and the reproductive data were analyzed.
METHODS
The pregnancy of the Sprague-Dawley rats (250+/-25 g) was determined by verifying the presence of the copulatory plug or sperm in the vaginal smear and the day on which this was observed was defined as pregnancy day 0. The pregnant rats were divided into three groups. The control group was intraperitoneally (ip) injected with sesame oil, and the other two groups were given either 150 or 750 mg/kg BW/day of toluene resuspended in sesame oil during pregnancy days 7-11 and 16-20. The rats from the three experimental groups were sacrificed on pregnancy days 11 and 20, respectively. The mRNA levels of the PRL-GH, Pit-1a and b isotype genes were analyzed by Northern blot hybridization and Reverse transcription-polymerase chain reaction (RT-PCR), respectively. The hormonal concentration was analyzed by Radioimmunoassay. The frequency of the placental trophoblast cells was determined by means of a histochemical study. Reproductive data, such as the placenta and infnat weight, pregnancy period and litter size were surveyed at pregnancy day 20 and after birth. Statistical analysis was carried out by means of the SAS program (version 8.1).
RESULTS
The mRNA levels of the PRL-GH family genes were reduced in a linear fashion by exposure to toluene. The mRNA levels of the Pit-1a and b isotype genes, which induce the expression of the PRL-GH family genes, were also reduced by exposure to toluene. The placental lactogen Iv and II concentrations in the rat placenta, fetus and maternal blood were also decreased by exposure to toluene. During the last stage of gestation, exposure to a high dose of toluene reduced the frequency of the spongiotrophoblast cells that secrete the PRL-GH hormones. Reproductive data such as the placenta and infant weight, and litter size were reduced, and the pregnancy period was extended in the toluene exposed group as compared with the control group.
CONCLUSIONS
Toluene disrupts the PRL-GH hormone metabolism in the rat placenta and this leads to reproductive disorder.

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Original Article
Effects of Cadmium on Placental Function and Reproduction in Rats
Jin Hong Ahn, Kwang Soo Ko, Chae Kwan Lee, Deog Hwan Moon, Byung Chul Son, Dae Hwan Kim, Chang Hee Lee, Hwi Dong Kim, Jung Won Kim, Jong Eun Kim, Jin Ho Chun, Chae Un Lee
Korean Journal of Occupational and Environmental Medicine 2004;16(3):236-249.   Published online September 30, 2004
DOI: https://doi.org/10.35371/kjoem.2004.16.3.236
AbstractAbstract PDF
OBJECTIVES
This study investigated the toxic effects of cadmium on placental function and reproduction in rats. For this study, the mRNA levels of the placental prolactin-growth hormone (PRL-GH) gene family, placental trophoblast cell frequemcy and reproductive data were analyzed.
METHODS
Pregnant F344 Fisher rats (200 g+/-23 g) were intraperitoneally injected with 0, 0.5, and 5.0 mg/kg B.W/day of cadmium (CdCl2) dissolved in saline from days 7-11 or 16-20 of pregnancy, and were sacrificed at days 11 or 20, respectively. The mRNA levels were analyzed by Northern blot hybridization and reverse transcription-polymerase chain reaction. The hormone concentration was analyzed by radioimmunoassay and the frequemcy of the placental trophoblast cells was observed by histochemical study. Reproductive data were surveyed at day 20 of the pregnancy and after the births. Statistical analysis was carried out using the SAS program (version 8.1).
RESULTS
The mRNA levels of the PRL-GH gene family were reduced dose dependently by cadmium. The mRNA levels of Pit-1a and -b isotype genes were also reduced by cadmium. The hormone concentration of PL-Iv and -II was decreased by cadmium. During the second half of pregnancy (days 11-21), a high dose of cadmium exposure significantly reduced the frequency of spongiotrophoblast and trophoblast giant cells that secrete the PRL-GH hormones. In the last stage of pregnancy (day 20), a high dose of cadmium exposure induced the apoptosis of spon-giotrophoblast cells in the junctional zone of the placenta. Reproductive data such as placental and infant weight, number of live fetuses were decreased, and number of resorptions and dead fetuses, post-implantation loss were increased significantly in the cadmium exposed group compared with the control.
CONCLUSIONS
Cadmium disrupts the functions of the placenta and these effects leads to reproductive disorders in rats.

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Original Article
Effects of Toluene, Xylene and Trichloroethylene on the Regulation of GnRH, GnRH Receptor and Pit-1 Gene Expression in Male Rat Hypothalamus and Pituitary
Dae Hwan Kim, Hun Lee, Chae Kwan Lee, Dae Sung Kang, Jung Ho Kim, Jong Tae Lee, Jin Ho Chun, Chae Un Lee, No Suk Ki
Korean Journal of Occupational and Environmental Medicine 1998;10(2):267-281.   Published online May 31, 1998
DOI: https://doi.org/10.35371/kjoem.1998.10.2.267
AbstractAbstract PDF
The workplace exposure of chemicals has steadily increased, therefore the concern for subsequent effect on reproductive outcome has been an important issue in occupational medicine. In previous studies, higher rates of spontaneous abortion, reduced fertility and menstrual disorder among women, and an impairment of sperm quantity and quality among men have been associated with a wide variety of chemical agents. This study was conducted to evaluate the effects of toluene, xylene and trichloroethylene (TCE) injection on the mRNA levels of GnRH, GnRH receptor and Pit-1 genes in male rats hypothalamus and pituitary and the effects on the plasma levels of FSH, LH, prolactin and testosterone. Sprague-Dawley male rats were divided into five groups of five each according to concentration of toluene, xylene and TCE. The rats were injected subcutaneously to 0, 50, 100, 200, 400 mg/kg body weight/day of toluene, xylene and TCE, respectively for 6 days. Rat brains were excised and hypothalamus and pituitary were separated. Reverse transcription-polymerase chain reaction (RT-PCR) and RNase protection assay (RPA) were used to evaluate the GnRH, GnRH receptor and Pit-1 mRNA levels. Plasma concentrations of FSH, LH, prolactin and testosterone were assayed by radioimulunoassay (RIA). The results were as follows; 1. GnRH, GnRH receptor and Pit-1 mRNA levels in toluene and xylene injected groups, and GnRH receptor mRNA levels in TCE injected group were lowered dose-dependently. Especially, GnRH receptor and Pit-1 mRNA levels in 200 mg/kg of toluene injected group, and GnRH, GnRH receptor and Pit-1 mRNA levels in 400 mg/kg of toluene injected group were significantly lowed than control group (p<0.05). GnRH receptor and Pit-1 mRNA levels in 400 mg/kg of xylene injected group, and GnRH receptor mRNA levels in 400 mg/kg of TCE injected group were significantly lower than control group (p<0.05). 2. The plasma levels of prolactin and testosterone in 400 mg/kg of toluene injected group, and LH in 100, 200 and 400 mg/kg of xylene injected group, and testosterone in 400 mg/kg of TCE injected group were significantly lower than control group (p<0.05). In conclusion, we speculated that toluene and xylene affected reproductive system secondarily through hypothalamus-pituitary axis, and TCE affected directly through steroidogenesis. And we recomended that further study for assessment of the reproductive toxiclty of mixed organic solvent exposures should be conducted.

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