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On-line Access: 2022-06-16

Received: 2021-12-07

Revision Accepted: 2022-05-04

Crosschecked: 2022-09-16

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Bin YU


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Journal of Zhejiang University SCIENCE B

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Reduced cell invasion may be a characteristic of placental defects in pregnant women of advanced maternal age at single-cell level

Author(s):  Bin ZHANG, Feng ZHANG, Fengying LU, Jing WANG, Wenbai ZHOU, Huihui WANG, Bin YU

Affiliation(s):  Department of Medical Genetics, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China

Corresponding email(s):  binyu@njmu.edu.cn

Key Words:  Advanced maternal age (AMA); Pregnancy complications; Placenta; Trophoblast; Cell invasion; Serine protease inhibitor clade E member 1 (SERPINE1)

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Bin ZHANG, Feng ZHANG, Fengying LU, Jing WANG, Wenbai ZHOU, Huihui WANG, Bin YU. Reduced cell invasion may be a characteristic of placental defects in pregnant women of advanced maternal age at single-cell level[J]. Journal of Zhejiang University Science B, 2022, 23(3): 747-759.

@article{title="Reduced cell invasion may be a characteristic of placental defects in pregnant women of advanced maternal age at single-cell level",
author="Bin ZHANG, Feng ZHANG, Fengying LU, Jing WANG, Wenbai ZHOU, Huihui WANG, Bin YU",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Reduced cell invasion may be a characteristic of placental defects in pregnant women of advanced maternal age at single-cell level
%A Fengying LU
%A Jing WANG
%A Wenbai ZHOU
%A Huihui WANG
%A Bin YU
%J Journal of Zhejiang University SCIENCE B
%V 23
%N 9
%P 747-759
%@ 1673-1581
%D 2022
%I Zhejiang University Press & Springer

T1 - Reduced cell invasion may be a characteristic of placental defects in pregnant women of advanced maternal age at single-cell level
A1 - Bin ZHANG
A1 - Feng ZHANG
A1 - Fengying LU
A1 - Jing WANG
A1 - Wenbai ZHOU
A1 - Huihui WANG
A1 - Bin YU
J0 - Journal of Zhejiang University Science B
VL - 23
IS - 9
SP - 747
EP - 759
%@ 1673-1581
Y1 - 2022
PB - Zhejiang University Press & Springer
ER -

The mechanisms underlying pregnancy complications caused by advanced maternal age (AMA) remain unclear. We analyzed the cellular signature and transcriptomes of human placentas in AMA women to elucidate these mechanisms. Placental tissues from two AMA women and two controls were used for single-cell RNA-sequencing (scRNA-seq). Controls consisted of AMA women who did not experience any pregnancy complications and pregnant women below the age of 35 years without pregnancy complications. Trophoblast cells were obtained from the placentas of another six pregnant women (three AMA women and three controls), and in-vitro transwell assays were conducted to observe the cell invasion ability. Thirty additional samples (from 15 AMA women and 15 controls) were analyzed to verify the specific expression of serine protease inhibitor clade E member 1 (SERPINE1). Preliminary study of the role of SERPINE1 in cell invasion was carried out with HTR8-S/Vneo cells. High-quality transcriptomes of 27‍607 cells were detected. Three types of trophoblast cells were detected, which were further classified into eight subtypes according to differences in gene expression and Gene Ontology (GO) function. We identified 110 differentially expressed genes (DEGs) in trophoblast cells between the AMA and control groups, and the DEGs were enriched in multiple pathways related to cell invasion. In-vitro transwell assays suggested that the invading trophoblast cells in AMA women were reduced. SERPINE1 was specifically expressed in the trophoblast, and its expression was higher in AMA women (P<0.05). Transfection of human SERPINE1 (hSERPINE1) into HTR8-S/Vneo trophoblast cells showed fewer invading cells in the hSERPINE1 group. Impaired cell invasion may underlie the increased risk of adverse pregnancy outcomes in AMA women. Abnormal expression of SERPINE1 in extravillous trophoblast (EVT) cells appears to play an important role.


目的:目前高龄孕妇(advanced maternal age,AMA)妊娠风险增高的原因尚不清楚,本研究从单细胞水平解析AMA孕妇胎盘的细胞组成与转录组特征。


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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