Potential endocrine disrupting effect of ochratoxin A on human placental 3β-hydroxysteroid dehydrogenase/isomerase in JEG-3 cells at levels relevant to human exposure

Ochratoxin A (OTA) is a common foodborne mycotoxin. Besides its classical toxicities, it is also associated with the impairment of steroidogenesis in rats. It is hypothesized that OTA may act as an endocrine disruptor by intervening 3β-hydroxysteroid dehydrogenase/isomerase (3β-HSD). To address this hypothesis, human placental cells JEG-3 were used in vitro to examine the effects of short- and long-term OTA exposures on expression levels of 3β-HSD1 and progesterone secretion at 24–96 h. Results showed that both cytotoxic and non-cytotoxic levels of OTA induced 3β-HSD1 mRNA expression by 281–378% at 72 and 96 h. A significant induction (43–316%) of 3β-HSD1 protein expression was observed at 48, 72 and 96 h, and the progesterone production with the involvement of 3β-HSD1 was significantly increased by 22–89% after 48–96 h. This is the first study to demonstrate OTA up-regulates 3β-HSD1 expression in human placental cells, indicating the potential endocrine-disrupting property of OTA.

► Human type 1 3β-hydroxysteroid dehydrogenase was up-regulated after OTA exposure. ► First study reported that OTA affected steriodogenic enzyme in human placental cell. ► Selected OTA concentrations in this study were relevant to human exposure level.