Transcriptional Profiling of Maternal and Fetal Organs following Rat In Utero TCDD or TCDF Exposure

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.本研究报道了宫内暴露于2,3,7,8-四氯二苯并对二噁英（2,3,7,8-tetrachlorodibenzo-p-dioxin，TCDD）或2,3,7,8-四氯二苯并呋喃（2,3,7,8-tetrachlorodibenzofuran，TCDF）后，妊娠第20天大鼠孕肝、胎鼠雌雄肝脏、雄性胎鼠垂体及胎鼠睾丸的基于RNA测序（RNAseq）的转录组谱。本研究设置两类暴露模型：其一为妊娠大鼠于妊娠第6天至第20天接受梯度剂量的TCDD或TCDF暴露；其二为妊娠大鼠于妊娠第15天接受单次剂量的TCDD或TCDF暴露。本数据集可为二噁英类物质诱导的大鼠雄性生殖毒性作用模式提供数据支撑，该作用模式涉及胎鼠垂体（促性腺激素生成减少）与胎鼠睾丸（莱迪希细胞胆固醇合成及类固醇生成减少）中的关键事件，上述事件被推测可降低围产期塞尔托利细胞增殖，并最终导致精子发生水平下降。TCDF对上述预设关键事件未产生影响，这可能是由于其相较于TCDD具有更高的代谢清除速率。