Uterine damage induces placenta accreta and immune imbalance at the maternal-fetal interface in the mouse

Jiayi Zhou; Huanpeng Chen; Xiuting Xu; Yunyun Liu; Shengzhu Chen; Si Yang; Fang He; Bolan Yu

doi:10.1016/j.placenta.2022.01.002

Uterine damage induces placenta accreta and immune imbalance at the maternal-fetal interface in the mouse

Placenta. 2022 Mar 4:119:8-16. doi: 10.1016/j.placenta.2022.01.002. Epub 2022 Jan 11.

Authors

Jiayi Zhou¹, Huanpeng Chen¹, Xiuting Xu¹, Yunyun Liu¹, Shengzhu Chen¹, Si Yang¹, Fang He², Bolan Yu³

Affiliations

¹ Department of Obstetrics and Gynecology, China; BioResource Research Center, China; Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
² Department of Obstetrics and Gynecology, China; Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
³ Department of Obstetrics and Gynecology, China; BioResource Research Center, China; Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. Electronic address: yubolan-q@qq.com.

PMID: 35066308
DOI: 10.1016/j.placenta.2022.01.002

Abstract

Introduction: Placenta accreta spectrum (PAS) disorder is one of the major complications resulting in maternal death and serious adverse pregnancy outcomes. Uterine damage - principally that associated with cesarean section - is the leading risk factor for the development of PAS. However, the underlying pathogenesis of PAS related to uterine damage remains unclear.

Methods: For this study, we constructed a mouse PAS model using hysterotomy to simulate a cesarean section in humans. Pregnant mice were sacrificed on embryonic days 12.5 (E12.5) and E17.5. Trophoblast invasion and placental vascularization were analyzed using Hematoxylin-Eosin (H&E) staining and immunohistochemistry (IHC), and the proportions of immune cells at the maternal-fetal interface were analyzed using flow cytometry. We analyzed the expressions of genes in the decidua and placenta using RNA sequencing and subsequent validation by QPCR, and measured serum angiogenic factors by ELISA.

Results: Uterine damage led to increased trophoblast invasion and placental vascularization, with extensive changes to the immune-cell profiles at the maternal-fetal interface. The proportions of T and NK cells in the deciduas diminished significantly, with the decidual NK cells and M - 2 macrophages showing the greatest decline. The expression of TNF-α and IL4 was upregulated in the deciduas, while that of IFN-γ and IL10 was downregulated significantly. The expression of Mmp2, Mmp9, Mmp3, and Dock4 was significantly elevated in the placenta, and the serum levels of anti-angiogenic factors were significantly attenuated.

Discussion: Uterine damage can cause immune imbalance at the maternal-fetal interface, which may contribute to abnormal trophoblast invasion and enhanced vascularization of the mouse placenta.

Keywords: Immune cells; Maternal-fetal interface; PAS; Trophoblast invasion; Uterine damage.

Publication types

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

MeSH terms

Animals
Female
Maternal-Fetal Exchange / immunology*
Mice
Mice, Inbred C57BL
Neovascularization, Physiologic*
Obstetric Surgical Procedures / adverse effects*
Placenta Accreta / etiology*
Pregnancy
Random Allocation
Trophoblasts / physiology*