Inhibition of 11β-HSD2 expression by triclosan via induction of apoptosis in human placental syncytiotrophoblasts.

Abstract

Triclosan is widely used in personal care products for its broad spectrum of antimicrobial effects, but triclosan is a potential endocrine disruptor. 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is a cortisol-inactivating enzyme that is highly expressed in human placental syncytiotrophoblasts to ensure normal fetal development in the presence of high levels of maternal cortisol in pregnancy. We investigated the effects of triclosan on 11β-HSD2 and apoptosis and the relationship between these two events in human placental syncytiotrophoblasts. Primary human placental cytotrophoblasts were isolated from term placenta. After syncytialization, the levels of 11β-HSD2 and apoptosis-related proteins including caspase3, Bcl-2, and Bax were examined after treatment with triclosan from 0.001 μM to 10 μM or triclosan (0.1 μM) in the presence and absence of apoptosis inhibitor Z-VAD-FMK (30 μM) for 24 h. Triclosan inhibited 11β-HSD2 mRNA, protein and activity levels in a concentration-dependent manner from 0.001 to 10 μM with a significant inhibition at 0.01 μM and above. Concurrently, triclosan induced apoptosis of human placental syncytiotrophoblasts as demonstrated by observations of increased nuclear condensation, DNA fragmentation and pro-apoptosis proteins such as Bax and cleaved-caspase3, decreased pro-caspase-3 and anti-apoptosis protein such as Bcl-2. Blocking apoptosis with Z-VAD-FMK attenuated the inhibition of 11β-HSD2 by triclosan significantly. Triclosan may attenuate the expression of placental 11β-HSD2 via the induction of apoptosis of placental syncytiotrophoblasts. This is likely to disrupt the placental glucocorticoid barrier and impair fetal development.