Department of Obstetrics and Gynaecology, The University of Auckland, Auckland, 1142, New Zealand.
Department of Pediatrics, Women and Infants Hospital-Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
Sci Rep. 2017 Jul 27;7(1):6694. doi: 10.1038/s41598-017-07017-x.
In preeclampsia, the serum levels of transthyretin, a carrier protein for thyroxine, are elevated. Transthyretin isolated from preeclamptic serum is also aggregated and can induce preeclampsia-like symptoms in pregnant IL10 mice. Using western blotting, immunofluorescence, ELISA and qRT-PCR, we investigated the production of transthyretin by preeclamptic placentae and whether transthyretin is carried into the maternal circulation via placental extracellular vesicles. Both total and aggregated transthyretin were present in higher levels in preeclamptic placentae compared to normotensive placentae (p < 0.05, n = 7), however the levels of transythretin mRNA were not significantly different (n = 8). Preeclamptic placentae secreted similar levels of total transthyretin compared to normotensive placentae (2352 ± 2949 ng/mL vs. 3250 ± 1864 ng/mL, mean ± SD, p > 0.05, n = 8), however in preeclampsia, a significant proportion is vesicle-associated (~48% vs 0%). Increased levels of aggregated transthyretin were specifically associated to preeclamptic nano-vesicles (p < 0.02, n = 8). This study showed that the placenta actively produces transthyretin and in preeclampsia, a significant amount is extruded into the maternal circulation via placental exracellular vesicles. The increased aggregation of transthyretin in preeclampsia occurs at the post-transcriptional level and while preeclamptic nano-vesicles may be removing a toxic aggregated protein from the placenta, they may also be delivering aggregated transthyretin to specific maternal organs, contributing to the pathogenesis of preeclampsia.
在子痫前期中，甲状腺素运载蛋白转甲状腺素的血清水平升高。从子痫前期血清中分离出的转甲状腺素也发生聚集，并可在怀孕的 IL10 小鼠中诱导子痫前期样症状。通过 Western blot、免疫荧光、ELISA 和 qRT-PCR，我们研究了子痫前期胎盘产生转甲状腺素的情况，以及转甲状腺素是否通过胎盘细胞外囊泡进入母体循环。与正常血压胎盘相比，子痫前期胎盘中转甲状腺素的总水平和聚集水平均升高（p < 0.05，n = 7），但转甲状腺素 mRNA 水平无显著差异（n = 8）。与正常血压胎盘相比，子痫前期胎盘分泌的总转甲状腺素水平相似（2352 ± 2949ng/mL 与 3250 ± 1864ng/mL，平均值 ± 标准差，p > 0.05，n = 8），但在子痫前期中，相当一部分是囊泡相关的（~48%比 0%）。聚集的转甲状腺素水平的增加与子痫前期纳米囊泡特异性相关（p < 0.02，n = 8）。本研究表明胎盘主动产生转甲状腺素，在子痫前期中，大量转甲状腺素通过胎盘细胞外囊泡挤出进入母体循环。转甲状腺素在子痫前期中的聚集增加发生在转录后水平，虽然子痫前期纳米囊泡可能从胎盘去除一种毒性聚集蛋白，但它们也可能将聚集的转甲状腺素递送到特定的母体器官，导致子痫前期的发病机制。
