Zhang N, Wang W S, Li W J, Liu C, Wang Y, Sun K
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, PR China; Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, PR China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, PR China.
Placenta. 2015 May;36(5):575-80. doi: 10.1016/j.placenta.2015.02.008. Epub 2015 Feb 21.
Perfluorooctane sulfonate (PFOS) is widely used as surfactants, lubricants, adhesives, fire retardants and propellants. Animal experiments have shown that PFOS can potentially influence reproductive function. The objective of the present study was to investigate the effects of PFOS on the endocrine function of human placental syncytiotrophoblasts.
Primary human placental cytotrophoblasts were isolated from term placenta. After syncytialization, the levels of aromatase and apoptosis-related proteins including caspase3, Bcl-2 and Bax were examined after treatment with PFOS from 0.0001 μM to 1 μM or PFOS (0.1 μM) in the presence and absence of apoptosis inhibitor Z-VAD-FMK (30 μM) for 24 h.
PFOS suppressed aromatase level and the secretion of estradiol, hCG and progesterone in a concentration-dependent manner from 0.0001 μM to 1 μM with a significant inhibition at 0.001 μM and above in human placental syncytiotrophoblasts. Furthermore PFOS reduced cell viability and induced apoptosis in human placental syncytiotrophoblasts as revealed by increases of pro-apoptosis proteins such as Bax and cleaved-caspase3, and decreases of pro-caspase3 and anti-apoptosis protein Bcl-2. The apoptosis induced by PFOS was further illustrated by increased DNA fragmentation and nuclear condensation. Blocking apoptosis with pan-caspase inhibitor Z-VAD-FMK, the impairment of placental endocrine function by PFOS was restored.
These results indicate that PFOS may disrupt the secretion of hCG, progesterone and estradiol by human placental syncytiotrophoblasts via induction of apoptosis.
全氟辛烷磺酸（PFOS）被广泛用作表面活性剂、润滑剂、粘合剂、阻燃剂和推进剂。动物实验表明，PFOS可能会影响生殖功能。本研究的目的是探讨PFOS对人胎盘合体滋养层细胞内分泌功能的影响。
从足月胎盘中分离出原代人胎盘细胞滋养层细胞。在细胞融合后，用0.0001 μM至1 μM的PFOS或在存在和不存在凋亡抑制剂Z-VAD-FMK（30 μM）的情况下用PFOS（0.1 μM）处理24小时后，检测芳香化酶和凋亡相关蛋白（包括caspase3、Bcl-2和Bax）的水平。
在人胎盘合体滋养层细胞中，PFOS以浓度依赖的方式抑制芳香化酶水平以及雌二醇、hCG和孕酮的分泌，在0.001 μM及以上浓度时具有显著抑制作用。此外，PFOS降低了人胎盘合体滋养层细胞的活力并诱导其凋亡，表现为促凋亡蛋白如Bax和裂解的caspase3增加，以及前caspase3和抗凋亡蛋白Bcl-2减少。PFOS诱导的凋亡通过DNA片段化增加和核浓缩进一步得到证实。用泛半胱天冬酶抑制剂Z-VAD-FMK阻断凋亡后，PFOS对胎盘内分泌功能的损害得以恢复。
这些结果表明，PFOS可能通过诱导凋亡破坏人胎盘合体滋养层细胞分泌hCG、孕酮和雌二醇。
