期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 100, 期 4, 页码 E542-E549出版社
ENDOCRINE SOC
DOI: 10.1210/jc.2014-4376
关键词
-
资金
- Chinese National Key Basic Research Projects [2014CB943302, 2011CB944403]
- National Natural Science Foundation of China [81330018]
Context: Triclosan is widely used in personal care products for its broad spectrum of antimicrobial effects, but triclosan is a potential endocrine disruptor. 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-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 11 beta-HSD2 and apoptosis and the relationship between these two events in human placental syncytiotrophoblasts. Design: Primary human placental cytotrophoblasts were isolated from term placenta. After syncytialization, the levels of 11 beta-HSD2 and apoptosis-related proteins including caspase3, Bcl-2, and Bax were examined after treatment with triclosan from 0.001 mu M to 10 mu M or triclosan (0.1 mu M) in the presence and absence of apoptosis inhibitor Z-VAD-FMK (30 mu M) for 24 h. Results: Triclosan inhibited 11 beta-HSD2 mRNA, protein and activity levels in a concentration-dependent manner from 0.001 to 10 mu M with a significant inhibition at 0.01 mu M 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 11 beta-HSD2 by triclosan significantly. Conclusions: Triclosan may attenuate the expression of placental 11 beta-HSD2 via the induction of apoptosis of placental syncytiotrophoblasts. This is likely to disrupt the placental glucocorticoid barrier and impair fetal development.
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