Fetal rat exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduces epididymal sperm number involving altered pituitary-testicular hormonal signaling as the proposed mode-of-action (MOA). To evaluate this MOA and compare TCDD to 2,3,7,8-tetrachlorodibenzofuran (TCDF), an in utero rat exposure and study was conducted. Endpoints included congener tissue levels and transcriptomes of maternal liver and fetal liver, testis, and pituitary. Decreased gonadotropin subunit mRNAs levels (Lhb and Fshb) and enriched signaling pathways including GNRH Signaling and Calcium Signaling were observed in fetal pituitary after TCDD (but not TCDF) exposure. TCDD (but not TCDF) decreased fetal testis cholesterologenic and steroidogenic pathway genes. TCDD tissue concentrations in dam liver, dam adipose, and whole fetus were approximately 3- to 6-fold higher than TCDF. These results support a MOA for dioxin-induced rat male reproductive toxicity involving key events in both the fetal pituitary (e.g., reduced gonadotropin production) and fetal testis (e.g., reduced Leydig cell cholesterologenesis and steroidogenesis).

中文翻译：

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二恶英对大鼠生殖毒性的作用方式和相对效能为2,3,7,8-四氯二苯并-p-二恶英和2,3,7,8-四氯二苯并呋喃的特征为胎儿垂体和睾丸转录组谱。

胎儿大鼠暴露于2,3,7,8-四氯二苯并-对-二恶英（TCDD）会减少附睾的精子数量，涉及垂体-睾丸激素信号的改变，这是拟议的作用方式（MOA）。为了评估该MOA并将TCDD与2,3,7,8-四氯二苯并呋喃（TCDF）进行比较，进行了宫内大鼠暴露和研究。终点包括母体肝脏和胎儿肝脏，睾丸和垂体的同类组织水平和转录组。暴露于TCDD（而非TCDF）的胎儿垂体中观察到促性腺激素亚基mRNA水平（Lhb和Fshb）降低，信号传导途径丰富，包括GNRH信号传导和钙信号传导。TCDD（但不是TCDF）降低胎儿睾丸的胆固醇生成和类固醇生成途径基因。大坝肝脏，大坝脂肪，整个胎儿大约比TCDF高3至6倍。这些结果支持了二恶英诱导的大鼠雄性生殖毒性的MOA，涉及胎儿垂体（例如，促性腺激素生成减少）和胎儿睾丸（例如，Leydig细胞胆固醇生成和类固醇生成减少）中的关键事件。