Progesterone modulates CD4+ CD25+ FoxP3+ regulatory T Cells and TGF-β1 in the maternal-fetal interface of the late pregnant mouse

© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd..

OBJECTIVE: Progesterone supplementation is recommended to prevent spontaneous preterm birth (sPTB) in clinical practice. However, the exact mechanism is still unclear. This study aims to better understand the mechanisms that progesterone can prevent PTB.

METHODS: Late pregnant mice were given various doses of progesterone receptor antagonist mifepristone, and pregnancy outcomes were observed. Then, non-pregnant and pregnant mice were given a subcutaneous injection of 40 mg/kg progesterone and 5 mg/kg mifepristone, respectively. CD4+ CD25+ FoxP3+ Treg cells in peripheral blood and decidua basalis were detected by FACS. Expressions of FoxP3 and TGF-β1 in the decidua basalis were detected.

RESULTS: Mifepristone induced preterm birth, and an obvious dose-response was found. Proportions of CD4+ CD25+ FoxP3+ Treg cells in the peripheral blood of non-pregnant mice increased significantly after progesterone injection. CD4+ CD25+ FoxP3+ Treg cells in the peripheral blood of pregnant mice increased significantly compared with those of non-pregnant mice. In pregnant mice, mifepristone significantly decreased the proportions of CD4+ CD25+ FoxP3+ Treg cells in peripheral blood, and reduced proportions of Treg cells at the maternal-fetal interface and expressions of FoxP3 and TGF-β1 in the maternal-fetal interface. Total 40 mg/kg of progesterone did not increase CD4+ CD25+ FoxP3+ Treg in the peripheral blood of pregnant mice, but increased proportions of Treg cells at the maternal-fetal interface and up-regulated FoxP3 and TGF-β1 expressions in the maternal-fetal interface.

CONCLUSION: Progesterone promotes pregnancy immune homeostasis by up-regulating Treg cells and TGF-β1 expression in the maternal-fetal interface. It may be one of the mechanisms of progesterone in preventing sPTB.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:88

Enthalten in:

American journal of reproductive immunology (New York, N.Y. : 1989) - 88(2022), 2 vom: 25. Aug., Seite e13541

Sprache:

Englisch

Beteiligte Personen:

Yang, Qianqian [VerfasserIn]
Li, Meihui [VerfasserIn]
Zhao, Ming [VerfasserIn]
Lu, Feifan [VerfasserIn]
Yu, Xiaomin [VerfasserIn]
Li, Li [VerfasserIn]
Gu, Zhongyi [VerfasserIn]
Deng, Yifang [VerfasserIn]
Guan, Rui [VerfasserIn]

Links:

Volltext

Themen:

320T6RNW1F
4G7DS2Q64Y
CD4+CD25+FoxP3+Treg cells
Forkhead Transcription Factors
Foxp3 protein, mouse
Interleukin-2 Receptor alpha Subunit
Journal Article
Mifepristone
Preterm birth
Progesterone
Research Support, Non-U.S. Gov't
TGF-β1
Transforming Growth Factor beta1

Anmerkungen:

Date Completed 15.07.2022

Date Revised 27.07.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1111/aji.13541

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM338687548