Time Course of Renal Transcriptomics after Subchronic Exposure to Ochratoxin A in Fisher Rats

• Main Authors: Laura Pastor, Ariane Vettorazzi, Elizabeth Guruceaga, López de Cerain A.
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: Toxins
• Subjects: ochratoxin A (OTA); sex differences; gene expression; metabolism; transporters; Fisher rats
• Online Access: https://www.mdpi.com/2072-6651/13/3/177

The mycotoxin ochratoxin A (OTA) is a potent nephrocarcinogen, mainly in male rats. The aim of this study was to determine the time course of gene expression (GeneChip^® Rat Gene 2.0 ST Array, Affymetrix) in kidney samples from male and female F344 rats, treated daily (p.o) with 0.50 mg/kg b.w. (body weight) of OTA for 7 or 21 days, and evaluate if there were differences between both sexes. After OTA treatment, there was an evolution of gene expression in the kidney over time, with more differentially expressed genes (DEG) at 21 days. The gene expression time course was different between sexes with respect to the number of DEG and the direction of expression (up or down): the female response was progressive and consistent over time, whereas males had a different early response with more DEG, most of them up-regulated. The statistically most significant DEG corresponded to metabolism enzymes (<i>Akr1b7</i>, <i>Akr1c2</i>, <i>Adh6</i> down-regulated in females; <i>Cyp2c11</i>, <i>Dhrs7</i>, <i>Cyp2d1</i>, <i>Cyp2d5</i> down-regulated in males) or transporters (<i>Slc17a9</i> down-regulated in females; <i>Slco1a1</i> (OATP-1) and <i>Slc51b</i> and <i>Slc22a22</i> (OAT) down-regulated in males). Some of these genes had also a basal sex difference and were over-expressed in males or females with respect to the other sex.