Ochratoxin A at low concentrations inhibits in vitro growth of canineumbilical cord matrix mesenchymal stem cells through oxidativechromatin and DNA damage

Ochratoxin A (OTA) exposure during pregnancy in laboratory animals induces delayed/abnormal embryodevelopment. Foetal adnexa-derived mesenchymal stem cells (MSCs) could help evaluate the devel-opmental risk of exposure to chemicals in advanced gestational age. We tested the effects of OTA atconcentrations ranging from 2.5 × 10-4to 25 nM on growth parameters of canine umbilical cord matrix(UCM)-derived MSCs. The hypothesis that oxidative chromatin and DNA damage could underlie OTA-mediated cell toxicity was also investigated. After in vitro exposure, OTA significantly decreased celldensity and increased doubling time in a passage- and concentration-dependent manner and no exposedcells survived beyond passage 5. Significantly higher rates of cells showed condensed and fragmentedchromatin and oxidized DNA, as assessed by OxyDNA assay. These findings showed that in vitro exposureto OTA, at picomolar levels, perturbs UCM-MSC growth parameters through oxidative chromatin andDNA damage, suggesting possible consequences on canine foetal development.