Genomic analysis of Fisher F344 rat kidneys from a reproductive study following dietary ochratoxin A exposure

Abstract

Ochratoxin A (OTA) is a mycotoxin produced by species of Penicillium and Aspergillus, and is found in many commodities including cereal grains, nuts, and coffee. OTA is a renal carcinogen and nephrotoxin at high concentrations, targeting the proximal tubules. This study uses transcriptomics and the previously reported apical data (Bondy et al., 2021) to infer mode-of-action of OTA toxicity in male and female rats exposed to low doses of OTA in utero and throughout development. Our findings support a male-specific activation of the innate and adaptive immune responses in F1 pups to OTA exposure. This was not found in the female F1 pups, and may be due to female-specific increased p38 activity and VDR signaling. Differentially expressed genes related to karyomegaly, MAPK activity, and immune activation appears to develop from in utero exposure to OTA whereas those related to decreased kidney and liver function, and changes to reproductive pathways occur in both rat generations. Together, these transcriptional results confirm that dietary exposure to OTA causes renal toxicity as well as alterations to hepatic and reproductive pathways in rats. In utero exposure of rats to OTA results in sex-specific alterations in immune response pathways, VDR signaling, and p38 activity.