Sequential activation of uterine epithelial IGF1R by stromal IGF1 and embryonic IGF2 directs normal uterine preparation for embryo implantation.
J Mol Cell Biol
; 13(9): 646-661, 2021 12 06.
Article
en En
| MEDLINE
| ID: mdl-34097060
ABSTRACT
Embryo implantation in both humans and rodents is initiated by the attachment of a blastocyst to the uterine epithelium. For blastocyst attachment, the uterine epithelium needs to transform at both the structural and molecular levels first, and then initiate the interaction with trophectoderm. Any perturbation during this process will result in implantation failure or long-term adverse pregnancy outcomes. Endocrine steroid hormones, which function through nuclear receptors, combine with the local molecules produced by the uteri or embryo to facilitate implantation. The insulin-like growth factor (IGF) signaling has been reported to play a vital role during pregnancy. However, its physiological function during implantation remains elusive. This study revealed that mice with conditional deletion of Igf1r gene in uteri suffered from subfertility, mainly due to the disturbed uterine receptivity and abnormal embryo implantation. Mechanistically, we uncovered that in response to the nidatory estrogen on D4 of pregnancy, the epithelial IGF1R, stimulated by the stromal cell-produced IGF1, facilitated epithelial STAT3 activation to modulate the epithelial depolarity. Furthermore, embryonic derived IGF2 could activate both the epithelial ERK1/2 and STAT3 signaling through IGF1R, which was critical for the transcription of Cox2 and normal attachment reaction. In brief, our data revealed that epithelial IGF1R was sequentially activated by the uterine stromal IGF1 and embryonic IGF2 to guarantee normal epithelium differentiation during the implantation process.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Implantación del Embrión
/
Factor I del Crecimiento Similar a la Insulina
/
Factor II del Crecimiento Similar a la Insulina
/
Receptor IGF Tipo 1
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Mol Cell Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2021
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA