title: Inhibition of 11β-HSD2 expression by triclosan via induction of apoptosis in human placental syncytiotrophoblasts.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  We investigated the effects of triclosan on 11β-HSD2 and apoptosis and the relationship between these two events in human placental syncytiotrophoblasts.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine (N.Z., W.W., W.L., C.L., K.S.), and Department of Obstetrics and Gynecology (N.Z., Y.C., Q.Y., Y.W.), Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China.
authors: Nan
authors: N
authors: Zhang
authors: Wangsheng
authors: W
authors: Wang
authors: Wenjiao
authors: W
authors: Li
authors: Chao
authors: C
authors: Liu
authors: Yunyan
authors: Y
authors: Chen
authors: Qianlan
authors: Q
authors: Yang
authors: Yu
authors: Y
authors: Wang
authors: Kang
authors: K
authors: Sun
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics* / Q000378:metabolism; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D010920:Placenta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D014260:Triclosan / Q000494:pharmacology*; D014327:Trophoblasts / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000891:Anti-Infective Agents, Local; D014260:Triclosan; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2