Project description:We report the RNAseq-based transcriptome profiles of rat gestation day 20 dam liver, fetal male and female liver, fetal male pituitary, and fetal testis following in utero exposure to either 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 2,3,7,8-tetrachlorodibenzofuran (TCDF). Two exposure models were examined: 1) pregnant rats exposed to either a dose response series of TCDD or TCDF from gestation day 6 - 20 or 2) pregnant rats exposed to a single dose of TCDD or TCDF on gestation day 15. These data support a mode-of-action for dioxin-induced rat male reproductive toxicity involving key events in both the fetal pituitary (reduced gonadotropin production) and fetal testis (reduced Leydig cell cholesterologenesis and steroidogenesis) which are hypothesized to decrease perinatal Sertoli cell proliferation and culminate in reduced spermatogenesis. The lack of a TCDF effect on proposed key events may be due to a higher rate of metabolic clearance relative to TCDD.
Project description:2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes the many forms of reproductive toxicity, such as defects in sexual behaviors, in pups of which mother is exposed to this substance at lower doses. However, the mechanism underlying these defects remains to be clarified in spite of many researches conducted so far. Our previous studies have revealed that maternal treatment with TCDD attenuates the production of pituitary gonadotropins [luteinizing hormone (LH) and follicle-stimulating hormone] in the late fetuses, leading to the impairment of sexual behavior in adulthood. To identify the target genes for a fetal reduction in gonadotropin β-subunit, we performed DNA microarray analysis using the fetal pituitary and its regulatory organ, the hypothalamus. The result showed that TCDD induced histone deacetylases (HDACs), and altered the expression of genes including gonadotropin-releasing hormone and activin signaling in the fetal pituitary. Moreover, our data indicated that the increased deacetylation of histone due to HDAC induction plays a critical role for a dioxin-induced attenuation of LHβ in the fetal pituitary. This study suggests a novel molecular mechanism explaining dioxin-produced reproductive toxicity. Pregnant Wistar rats were orally treated with TCDD (1 µg/kg in corn oil) at gestational day (GD)15. Then, the total RNA was extracted from the fetal pituitary and hypothalamus at GD20. To identify the target genes the alteration of which contributes to a reduction in fetal gonadotropin β-subunit, the profile of gene expression was analyzed using the Illumina RatRef-12 Expression BeadChip.
Project description:Male Sprague-Dawley rats were used to establish exhausted-exercise model by motorized rodent treadmill. Yu-Ping-Feng-San at doses of 2.18 g/kg was administrated by gavage before exercise training for 10 consecutive days. Quantitative proteomics was performed for assessing the related mechanism of Yu-Ping-Feng-San.