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      • Effects of Perinatal Exposure to PhthalateI/Adipate Esters on Sex Steroid Levels and Hypothalamic Gene Expression during Early Postnatal Periods in Rats

        Hwi-Cheul Lee,Gi-Sun lm.,Hak Jae Chung.,Poong-Yeon Lee,Jin-Ki Park,Won-Kyong Chang,Boh-Suk Yang,Keitaro Yamanouchi,Masugi Nishihara 한국동물생명공학회(구 한국동물번식학회) 2006 Reproductive & developmental biology Vol.30 No.4

        Our previous research has identified granulin (grn) and p130 genes as sex steroidinducible genes in the rat hypothalamus, which might be involved in sexual differentiation of the brain. Phthalate esters that are used as plasticizers and also found at low levels in foods such as dairy products are often mentioned as suspected endocrine disrupters. The purpose of the present study is to elucidate whether perinatal exposure to dinbutyl phthalate (DBP), diisononyl phthalate (DINP) and di2ethylhexyl adipate (DEHA) affects hypothalamic sex steroidinducible genes. The present study assessed the effects of perinatal exposure to DBP, DINP and DEHA on sex steroid hormones levels and hypothalamic grn and p130 mRNA expressions at postnatal day (PND) 3 and 7. Pregnant rats were fed a soyfree diet containing 20, 200, 2,000 and 10,000 ppm of DBP, 40, 400, 4,000 and 20,000 ppm of DINP, or 480, 2,400 and 12,000 ppm of DEHA from gestational day (GD) 15 to GD 3 or 7. At PND 3 and 7, perinatal exposure to these chemicals did not substantially affect serum concentrations of testosterone and estradiol. At PND 3, the expression of grn mRNA levels in males was decreased by DEHA, and that of p130 was decreased by DBP, DINP and DEHA, though the effects were not dosedependent. At PND 7, the expression of grn gene in female pups was increased by higher doses of DBP and all the doses, except for 4,000 ppm, of DINP, while that in male pups decreased by 480 and 12,000 ppm of DEHA. Hypothalamic expression of p130 mRNA in males was increased by lower doses of DBP and all the doses of DINP, whereas that of females was decreased by 480 and 2,400 ppm of DEHA. These results suggest that these chemicals may affect the expression of grn and p130 genes by directly acting on the hypothalamus, thus leading to inappropriate expression of these genes.

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        Analysis of DNA Methyltransferases (Dnmts) Expression during Early Development

        Yeoung-Gyu KO,Jong-Mu Kim,Gi-Sun lm,Byoung-Chul Yang,Hwi-Cheul Lee,Hwan-Hoo Seong,Boh-Suk Yang,Hak-Jae chung 한국동물생명공학회(구 한국동물번식학회) 2006 Reproductive & developmental biology Vol.30 No.4

        There are replete numbers of reports which have apparently shown that established patterns of methylation are critical for normal mammalian development. Here, we report expression of the DNA methyltransferases (Dnmts) family during mouse early development. Transcription of Dnmt1o occurs in one-cell and morula stage embryos, whereas Dnmt1s transcripts were detectable in all cells and tissues examined during the study. Dnmt3a1 transcript was detected in all cells and Dnmt3a2 transcript was particularly detected in the oocyte and 1-cell stages. Low level Dnmt3b1 transcripts were expressed ubiquitously in oocyte, 1-cell, and preimplantation embryos except 2~4 cell stages. Dnmt3b3 transcripts were only detected in E7.5 embryo and ovary. Furthermore, Dnmt3l transcripts were detectable in all cells and tissues examined. Unlike Dnmt1, both Dnmt3a and Dnmt3b proteins existed in the nucleus of preimplantation embryos till the morula stage. These Results suggest that differences Dnmts expression level exist and genomic DNA methylation patterns may be determined partly through differential expression of Dnmts during early development.

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