Reduction of progesterone, estradiol and hCG secretion by perfluorooctane sulfonate via induction of apoptosis in human placental syncytiotrophoblasts.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
These results indicate that PFOS may disrupt the secretion of hCG, progesterone and estradiol by human placental syncytiotrophoblasts via induction of apoptosis.
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.
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Zhang
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.
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Wang
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.
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Li
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.
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Liu
Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, PR China. Electronic address: renjiwangyu@gmail.com.
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Y
Wang
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. Electronic address: sungangrenji@hotmail.com.
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Sun
D017738:Alkanesulfonic Acids / Q000633:toxicity*; D000590:Amino Acid Chloromethyl Ketones; D017209:Apoptosis / Q000187:drug effects*; D001141:Aromatase / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism*; D005466:Fluorocarbons / Q000633:toxicity*; D006801:Humans; D011374:Progesterone / Q000378:metabolism*; D014327:Trophoblasts / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
D017738:Alkanesulfonic Acids; D000590:Amino Acid Chloromethyl Ketones; D006063:Chorionic Gonadotropin; D005466:Fluorocarbons; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D011374:Progesterone; D004958:Estradiol; C076994:perfluorooctane sulfonic acid; D001141:Aromatase; D053148:Caspase 3
Apoptosis; Estradiol; PFOS; Placenta; Progesterone; hCG