Transforming growth factor beta signaling and decidual integrity in mice†.
Animals
Bone Morphogenetic Proteins
/ genetics
Cell Proliferation
Endometrium
/ physiology
Extracellular Signal-Regulated MAP Kinases
/ genetics
Female
Gene Expression Regulation
/ physiology
Gene Expression Regulation, Developmental
MAP Kinase Signaling System
Mice
Mice, Knockout
Receptor, Transforming Growth Factor-beta Type I
/ genetics
Signal Transduction
Transforming Growth Factor beta
/ genetics
Up-Regulation
Uterus
TGFBR1
TGFβ signaling
decidualization
endometrium
uterus
Journal
Biology of reproduction
ISSN: 1529-7268
Titre abrégé: Biol Reprod
Pays: United States
ID NLM: 0207224
Informations de publication
Date de publication:
01 12 2020
01 12 2020
Historique:
received:
02
03
2020
revised:
28
07
2020
accepted:
03
09
2020
pubmed:
10
9
2020
medline:
30
10
2021
entrez:
9
9
2020
Statut:
ppublish
Résumé
Transforming growth factor beta (TGFβ) signaling regulates multifaceted reproductive processes. It has been shown that the type 1 receptor of TGFβ (TGFBR1) is indispensable for female reproductive tract development, implantation, placental development, and fertility. However, the role of TGFβ signaling in decidual development and function remains poorly defined. Our objective is to determine the impact of uterine-specific deletion of Tgfbr1 on decidual integrity, with a focus on the cellular and molecular properties of the decidua during development. Our results show that the developmental dynamics of the decidua is altered in TGFBR1 conditionally depleted uteri from embryonic day (E) 5.5 to E8.5, substantiated by downregulation of genes associated with inflammatory responses and uterine natural killer cell abundance, reduced presence of nondecidualized fibroblasts in the antimesometrial region, and altered decidual cell development. Notably, conditional ablation of TGFBR1 results in the formation of decidua containing more abundant alpha smooth muscle actin (ACTA2)-positive cells at the peripheral region of the antimesometrial side versus controls at E6.5-E8.5. This finding is corroborated by upregulation of a subset of smooth muscle marker genes in Tgfbr1 conditionally deleted decidua at E6.5 and E8.5. Moreover, increased cell proliferation and enhanced decidual ERK1/2 signaling were found in Tgfbr1 conditional knockout mice upon decidual regression. In summary, conditional ablation of TGFBR1 in the uterus profoundly impacts the cellular and molecular properties of the decidua. Our results suggest that TGFBR1 in uterine epithelial and stromal compartments is important for the integrity of the decidua, a transient but crucial structure that supports embryo development.
Identifiants
pubmed: 32902612
pii: 5903309
doi: 10.1093/biolre/ioaa155
pmc: PMC7711917
doi:
Substances chimiques
Bone Morphogenetic Proteins
0
Transforming Growth Factor beta
0
Extracellular Signal-Regulated MAP Kinases
EC 2.7.11.24
Receptor, Transforming Growth Factor-beta Type I
EC 2.7.11.30
Tgfbr1 protein, mouse
EC 2.7.11.30
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1186-1198Subventions
Organisme : NIEHS NIH HHS
ID : P30 ES029067
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD042311
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD087236
Pays : United States
Organisme : NICHD NIH HHS
ID : U01 HD042311
Pays : United States
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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