SWATH proteomics analysis of placental tissue with intrahepatic cholestasis of pregnancy

Yuxuan Jiang; Xiaoping Yin; Qian Xu; Xiaoxiao Tang; Huajie Zhang; Xueshan Cao; Jing Lin; Yi Wang; Fei Yang; Naseer Ullah Khan; Liming Shen; Danqing Zhao

doi:10.1016/j.placenta.2023.04.009

SWATH proteomics analysis of placental tissue with intrahepatic cholestasis of pregnancy

Placenta. 2023 Jun:137:1-13. doi: 10.1016/j.placenta.2023.04.009. Epub 2023 Apr 8.

Authors

Yuxuan Jiang¹, Xiaoping Yin¹, Qian Xu¹, Xiaoxiao Tang², Huajie Zhang², Xueshan Cao², Jing Lin², Yi Wang³, Fei Yang¹, Naseer Ullah Khan², Liming Shen⁴, Danqing Zhao⁵

Affiliations

¹ Department of Obstetrics and Gynecology Affiliated Hospital of Guizhou Medical University, Guiyang, China.
² College of Life Science and Oceanography, Shenzhen University, Shenzhen, China.
³ School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, China.
⁴ College of Life Science and Oceanography, Shenzhen University, Shenzhen, China. Electronic address: slm@szu.edu.cn.
⁵ Department of Obstetrics and Gynecology Affiliated Hospital of Guizhou Medical University, Guiyang, China. Electronic address: zhaodanqing2823@163.com.

PMID: 37054625
DOI: 10.1016/j.placenta.2023.04.009

Abstract

Introduction: Intrahepatic cholestasis of pregnancy (ICP) usually occurs in the second and third trimesters. The disease's etiology and diagnostic criteria are currently unknown. Based on a sequence window to obtain all theoretical fragment ions (SWATH) proteomic approach, this study sought to identify potential proteins in placental tissue that may be involved in the pathogenesis of ICP and adverse fetal pregnancy outcomes.

Methods: The postpartum placental tissue of pregnant women with ICP were chosen as the case group (ICP group) (subdivided into mild ICP group (MICP group) and severe ICP group (SICP group)), and healthy pregnant women were chosen as the control group (CTR). The hematoxylin-eosin (HE) staining was used to observe the histologic changes of placenta. The SWATH analysis combined with liquid chromatography-tandem mass spectrometry (LC-MS) was used to screen the differentially expressed proteins (DEPs) in ICP and CTR groups, and bioinformatics analysis was used to find out the biological process of these differential proteins.

Results: Proteomic studies showed there were 126 DEPs from pregnant women with ICP and healthy pregnant women. Most of the identified proteins were functionally related to humoral immune response, cell response to lipopolysaccharide, antioxidant activity and heme metabolism. A subsequent examination of placentas from patients with mild and severe ICP revealed 48 proteins that were differentially expressed. Through death domain receptors and fibrinogen complexes, these DEPs primarily regulate extrinsic apoptotic signaling pathways, blood coagulation, and fibrin clot formation. The differential expressions of HBD, HPX, PDE3A, and PRG4 were down-regulated by Western blot analysis, which was consistent with proteomics.

Discussion: This preliminary study helps us to understand the changes in the placental proteome of ICP patients, and provides new insights into the pathophysiology of ICP.

Keywords: Intrahepatic cholestasis of pregnancy; Pathophysiology; Placenta; Proteomics; SWATH.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cholestasis, Intrahepatic* / metabolism
Female
Humans
Placenta / metabolism
Pregnancy
Pregnancy Complications* / metabolism
Pregnancy Outcome
Proteomics

Supplementary concepts

Intrahepatic Cholestasis of Pregnancy