Thyroid hormone transport and metabolism are disturbed in the placental villi of miscarriage.

BACKGROUND: It has been long known that thyroid hormone regulates placental villi development, which is associated with the occurrence of miscarriage. However, whether abnormal thyroid hormone metabolism and transport in placental villi are involved in miscarriage is still to be verified. METHODS: Placental villi of elective terminations of pregnancies (ETPs) and miscarriage were collected. Proliferative activity and apoptosis of villi trophoblasts and angiogenesis were detected by TUNEL and immunochemistry. The expressions of thyroid hormone receptors (THRs), transthyretin (TTR), monocarboxylate transporter 8 (MCT8), organic anion transporting polypeptides 1A1 (OATP1A1), deiodinase 2 (Dio2) and Dio3 were examined by RT-PCR, Western blot, immunohistochemistry and immunofluorescence. JEG3 cell was treated with iopanoic acid (IOP), an inhibitor of Dio2 activity, the expressions of Dio2, placenta growth factor (PLGF) and sFlt1 were detected by RT-PCR and Western blot. RESULTS: Cell proliferation was suppressed and apoptosis was increased in placental villi cytotrophoblasts of miscarriage. CD34+ vessel number and vascular endothelial growth factor (VEGF) protein abundance were decreased in miscarriage. In miscarriage group, the gene expression of Dio2, Dio3, TTR and THRα, but not THRß, MCT8 and OATP1A1, were downregulated. The protein abundances of TTR and THRα were downregulated in miscarriage group, but not THRß. The protein abundance of Dio2 in miscarriage villi was decreased compared with that in ETP. In JEG3 cells, the gene expression of PLGF was decreased and the expression of sFlt1 was increased in IOP treatment; The protein abundance of Dio2 was downregulated but the gene expression of Dio2 was unaffected in IOP treatment. CONCLUSION: Thyroid hormone transport and metabolism in miscarriage were disturbed and may impaired angiogenesis of placental villi, which was associated with the occurrence of miscarriage.

STAT3 signaling pathway is involved in the pathogenesis of miscarriage.

INTRODUCTION: The STAT3 signaling pathway plays an important role in the migration and invasion of villous trophoblast cells. In early miscarriage, the activation of STAT3 has been confirmed to decline, but its effect in early pregnancy has not received much attention. METHODS: The number of trophoblast cells were detected by HE staining in 30 cases of earlymiscarriage, 20 cases of recurrent miscarriage and 30 cases of control group.The protein levels of CyclinD1, VEGF, VEGFR1, Ki67, CD34 and phosphorylated STAT3 in three groups weredetected by immunohistochemistry or Western blot.Consistently, the mRNA levels of them weredetected by qPCR. The expression of STAT3 signaling pathway on trophoblast cells were evaluated in HTR-8/SVneo cell treated by AG490. Additionally, we established the situation of AG490-induced STAT3 signaling pathway inhibited in HTR-8/SVneo cell as well. RESULTS: HE staining showed that the number of trophoblast cells in the two study groups were significantly lower than that in the control group. The expression of STAT3 and its down stream target gene, such as CyclinD1, VEGF were significantly downregulated in abortion tissues (villi and decidua) in patients with early miscarriage. In vitro, AG490 inhibited the growth of trophoblast cells and promoted apoptosis of them by inhibiting STAT3 signaling pathway. DISCUSSION: The STAT3 signaling pathway might be involved in the pathogenesis of earlymiscarriage.However, further experiments are still needed to verify whether inhibitors of the STAT3 pathway can be used as drug treatment targets for spontaneous abortion.

Exosomes Derived from Umbilical Cord Mesenchymal Stem Cells Alleviate Mifepristone-Induced Human Endometrial Stromal Cell Injury.

The human endometrial stromal cells (hEndoSCs) could maintain endometrial homeostasis and play a critical role in repairing endometrial injury. Mesenchymal stem cells (MSCs) significantly increase the proliferation of damaged hEndoSCs and protect them from apoptosis. Recent studies indicated that exosomes derived from stem cells could be recruited to damaged tissues for regeneration, which exhibit the potential for stem cell therapy as therapeutic vectors. In this study, we isolated human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) and investigated the effects of hUCMSC-Exos on mifepristone-induced hEndoSC injury. Exosome uptake and cell proliferation as well as cell apoptosis of damaged hEndoSCs treated with hUCMSC-Exos were detected. We also assessed the expression of apoptosis-related proteins and the PTEN/AKT signaling pathway. We found hUCMSC-Exos improved the proliferation of damaged hEndoSCs and protected hEndoSCs from the mifepristone-induced apoptosis. hUCMSC-Exos upregulated Bcl-2 level as well as downregulated Cleaved Caspase-3 level and activated the PTEN/AKT signaling pathway to regulate the proliferation and antiapoptosis. These results indicated hUCMSC-Exos protected hEndoSCs from mifepristone-induced apoptosis and played an active role in repairing the damaged hEndoSCs through the PTEN/AKT signaling pathway in vitro. hUCMSC-Exos may hold great promise in the cell-free therapy of endometrial injury.