Department of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450007, Henan, PR China.
Stem Cell Regenerative Medicine Transformation Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450007, Henan, PR China.
Placenta. 2024 Feb;146:30-41. doi: 10.1016/j.placenta.2023.12.022. Epub 2023 Dec 28.
Fetal growth restriction (FGR) can lead to fetal mental development abnormalities, malformations, and even intrauterine death. Defects in the trophoblasts at the maternal-fetal interface may contribute to FGR. However, the impact of trophoblasts on FGR is still not well understood. Therefore, the objective of this study is to characterize the heterogeneity of placental cells at the single-cell level and investigate the role of trophoblast subtypes in the pathogenesis of FGR at the cellular and molecular levels.
Single-cell RNA sequencing was performed on the maternal side of placentas from two normal pregnant women and two pregnant women with FGR. Lentivirus transfection was used to establish a FN1 knockout model in trophoblast HTR-8-Svneo cells. The effect of FN1 knockout on cell migration and invasion of HTR-8-Svneo cells was assessed through wound healing and transwell assays.
Nine cell types were annotated in 39,161 cells derived from single-cell RNA sequencing. The FGR group exhibited a decrease in the percentage of trophoblasts, especially in subtype of extravillous trophoblasts (EVTs). The expression of FN1 was reduced in trophoblasts and EVTs. Furthermore, the protein expression levels of FN1 in the placentas of FGR patients were significantly lower than those of normal pregnant women. The cell migration and invasion ability of HTR-8-Svneo cells were inhibited after the knockdown of FN1.
The dysregulation of the trophoblast subtype-EVTs is involved in placental dysplasia related to FGR. The association between aberrant placental trophoblasts and reduced FN1 expression may contribute to insufficient remodeling of spiral arteries and the formation of FGR.
胎儿生长受限（FGR）可导致胎儿精神发育异常、畸形，甚至宫内死亡。母体-胎儿界面的滋养层缺陷可能导致 FGR。然而，滋养层对 FGR 的影响仍不清楚。因此，本研究的目的是在单细胞水平上描述胎盘细胞的异质性，并在细胞和分子水平上研究滋养细胞亚型在 FGR 发病机制中的作用。
对两名正常孕妇和两名 FGR 孕妇的胎盘母侧进行单细胞 RNA 测序。使用慢病毒转染在滋养细胞 HTR-8-Svneo 细胞中建立 FN1 敲除模型。通过划痕愈合和 Transwell 测定评估 FN1 敲除对 HTR-8-Svneo 细胞迁移和侵袭的影响。
从单细胞 RNA 测序中得到的 39161 个细胞中注释了 9 种细胞类型。FGR 组中滋养细胞，尤其是绒毛外滋养细胞（EVTs）的比例下降。FN1 在滋养细胞和 EVTs 中的表达减少。此外，FGR 患者胎盘组织中 FN1 的蛋白表达水平明显低于正常孕妇。FN1 敲低后，HTR-8-Svneo 细胞的迁移和侵袭能力受到抑制。
滋养细胞亚型-EVTs 的失调与 FGR 相关的胎盘发育不良有关。异常胎盘滋养细胞与 FN1 表达减少之间的关联可能导致螺旋动脉重塑不足和 FGR 的形成。
