Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Hefei, 230022, Anhui, China.
NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No.81 Meishan Road, Hefei, 230032, Anhui, China.
Reprod Biol Endocrinol. 2023 Nov 15;21(1):108. doi: 10.1186/s12958-023-01142-1.
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.
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.
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 THRβ, MCT8 and OATP1A1, were downregulated. The protein abundances of TTR and THRα were downregulated in miscarriage group, but not THRβ. 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.
Thyroid hormone transport and metabolism in miscarriage were disturbed and may impaired angiogenesis of placental villi, which was associated with the occurrence of miscarriage.
长期以来，人们一直认为甲状腺激素调节胎盘绒毛的发育，这与流产的发生有关。然而，胎盘绒毛中甲状腺激素代谢和转运的异常是否参与流产仍有待验证。
收集选择性终止妊娠（ETP）和流产的胎盘绒毛。通过 TUNEL 和免疫化学检测绒毛滋养层的增殖活性和凋亡以及血管生成。通过 RT-PCR、Western blot、免疫组化和免疫荧光检测甲状腺激素受体（THR）、转甲状腺素蛋白（TTR）、单羧酸转运蛋白 8（MCT8）、有机阴离子转运多肽 1A1（OATP1A1）、脱碘酶 2（Dio2）和 Dio3 的表达。用碘帕醇（IOP）处理 JEG3 细胞，一种 Dio2 活性抑制剂，通过 RT-PCR 和 Western blot 检测 Dio2、胎盘生长因子（PLGF）和 sFlt1 的表达。
流产胎盘绒毛滋养层细胞增殖受到抑制，凋亡增加。流产组 CD34 血管数和血管内皮生长因子（VEGF）蛋白丰度降低。在流产组中，Dio2、Dio3、TTR 和 THRα 的基因表达下调，但 THRβ、MCT8 和 OATP1A1 基因表达未下调。TTR 和 THRα 的蛋白丰度在流产组中下调，但 THRβ 蛋白丰度未下调。与 ETP 相比，流产绒毛中 Dio2 的蛋白丰度降低。在 JEG3 细胞中，IOP 处理后 PLGF 的基因表达降低，sFlt1 的表达增加；IOP 处理后 Dio2 蛋白丰度下调，但 Dio2 基因表达不受影响。
流产时甲状腺激素的转运和代谢受到干扰，可能损害胎盘绒毛的血管生成，这与流产的发生有关。
