Bile Acid Stress Disrupts Homeostasis and Placental Functional Programs in Human First-Trimester Trophoblast Organoids
- 1International Peace Maternal and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
- 2Shanghai Key Laboratory of Embryo Original Diseases, Shanghai 200030, China
- 3Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Abstract
Intrahepatic cholestasis of pregnancy (ICP) is characterized by elevated maternal bile acids (BAs), yet their effects on human trophoblast organization and transcriptional responses remain incompletely understood. Here, we used human first-trimester trophoblast organoids (TOs) to characterize cellular and transcriptional responses to a defined six-component BA mixture (50–150 μM). BA exposure disrupted organoid architecture and intercellular organization, with attenuated proliferation-associated features and more prominent SDC1 staining. These changes were accompanied by increased DNA fragmentation and cleaved caspase-3 staining and by reduced ATP-dependent viability, supporting an apoptotic component of BA-associated trophoblast injury. Bulk RNA sequencing after exposure to 150 μM BA for 96 h identified 413 differentially expressed genes, of which 364 were downregulated and 49 were upregulated. Downregulated transcripts were primarily associated with placental endocrine and secretory processes, epithelial organization, cell adhesion, and transport, whereas a smaller subset of lipid-handling genes was upregulated. RT-qPCR confirmed concordant upregulation of PLIN2 and ABCG1 in two independent donor-derived TO lines. Collectively, these findings show that BA mixture exposure is associated with structural injury and altered transcriptional profiles in human TOs, thereby providing insight into trophoblast responses to BA stress.
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BibTeX
@article{zhang2026bile,
title = {{Bile Acid Stress Disrupts Homeostasis and Placental Functional Programs in Human First-Trimester Trophoblast Organoids}},
author = {Shutian Zhang and Li Li and Sili Zheng and Qing Xu and Zhida Qian and Jingjing Su and Weibin Wu},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms272110023},
url = {https://www.mdpi.com/1422-0067/27/21/10023},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Bile Acid Stress Disrupts Homeostasis and Placental Functional Programs in Human First-Trimester Trophoblast Organoids
AU - Shutian Zhang
AU - Li Li
AU - Sili Zheng
AU - Qing Xu
AU - Zhida Qian
AU - Jingjing Su
AU - Weibin Wu
PY - 2026
DA - 2026/11/09
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms272110023
UR - https://www.mdpi.com/1422-0067/27/21/10023
AB - Intrahepatic cholestasis of pregnancy (ICP) is characterized by elevated maternal bile acids (BAs), yet their effects on human trophoblast organization and transcriptional responses remain incompletely understood. Here, we used human first-trimester trophoblast organoids (TOs) to characterize cellular and transcriptional responses to a defined six-component BA mixture (50–150 μM). BA exposure disrupted organoid architecture and intercellular organization, with attenuated proliferation-associated features and more prominent SDC1 staining. These changes were accompanied by increased DNA fragmentation and cleaved caspase-3 staining and by reduced ATP-dependent viability, supporting an apoptotic component of BA-associated trophoblast injury. Bulk RNA sequencing after exposure to 150 μM BA for 96 h identified 413 differentially expressed genes, of which 364 were downregulated and 49 were upregulated. Downregulated transcripts were primarily associated with placental endocrine and secretory processes, epithelial organization, cell adhesion, and transport, whereas a smaller subset of lipid-handling genes was upregulated. RT-qPCR confirmed concordant upregulation of PLIN2 and ABCG1 in two independent donor-derived TO lines. Collectively, these findings show that BA mixture exposure is associated with structural injury and altered transcriptional profiles in human TOs, thereby providing insight into trophoblast responses to BA stress.
SN - 1422-0067
ER -