Published: 25-08-2019| Version 1 | DOI: 10.17632/9vr5rb99d2.1
Kamin Johnson


Fetal rat exposure to TCDD reduces epididymal sperm number and a proposed mode-of-action (MOA) involves altered pituitary-testicular hormonal signaling. To evaluate this MOA and compare TCDD and TCDF congeners, an in utero rat exposure and evaluation model was used. 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).