목적: 이 연구는 톨루엔이 흰쥐의 태반 기능과 태자의 발생에 미치는 영향을 연구하고자 하였다. 방법: 실험동물은 1 5주령의 임신된 Sprague-Dawley 흰쥐(250±25 g) 를 사용하였다. 실험군은 대조군과 톨루엔 150 mg/kg BW 투여군, 750㎎/㎏ BW 투여군 등 3군으로 구분하였으며, 톨루엔은 참기름과 섞은 뒤 복강주사하였다. 유전자 발현은 Northern blot hybridization과 reverse transcription-polymerase chain reaction (RTPCR)방법으로 조사하였으며, 호르몬 농도는 방사선면역측정법으로, 태반세포의 빈도는 조직병리학적 소견으로 관찰하였으며, 발생학적 자료는 태반과 태자의 무게, 임신기간, 태자의 수 등을 조사하였다. 자료의 통계적 분석에는 SAS (version 8.1)를 사용하였다. 결과: 톨루엔은 투여농도에 비례하여 흰쥐 태반의 PRL-GH군 유전자 발현을 억제하였으며, 이군 유전자들의 전사조절인자인 Pit-1a, b 유전자의 발현도 억제하였다. 그리고 PRL-GH군의 placental lactogen I, Iv, Ⅱ 호르몬의 농도를 감소시켰다. 톨루엔 750 ㎎ 투여군 태반의 이음구역(junctional zone)은 PRL-GH군 호르몬을 분비하는 spon-giotrophoblast세포의 빈도가 감소되었다. 톨루엔은 태반과 태자의 무게를 감소시켰고 임신기간을 증가시켰으며 태자의 수를 감소시켰다. 결론: 임신 중 톨루엔 노출은 PRL-GH군 호르몬 분비를 교란시켜 흰쥐의 태반기능과 태자발생의 장해요인으로 작용한다.
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 ㎎/㎏ 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.
