Roles of ERα during mouse trophectoderm lineage differentiation: revealed by antagonist and agonist of ERα

Abstract

During mouse early embryogenesis, blastomeres increase in number by the morula stage. Among them, the outer cells are polarized and differentiated into trophectoderm (TE), while the inner cells remain unpolarized and give rise to inner cell mass (ICM). TE provides an important liquid environment for ICM development. In spite of extensive research, the molecular mechanisms underlying TE formation are still obscure. In order to investigate the roles of estrogen receptor a (ERa) in this course, mouse 8-cell embryos were collected and cultured in media containing ERa specific antagonist MPP and/or agonist PPT. The results indicated that MPP treatment inhibits blastocyst formation in a dose-dependent manner, while PPT, at proper concentration, promotes the cavitation ratio of mouse embryos. Immunofluorescence staining results showed that MPP significantly decreased the nuclear expression of CDX2 in morula, but no significant changes of OCT4 were observed. Moreover, after MPP treatment, the expression levels of the genes related to TE specification, Tead4, Gata3 and Cdx2, were significantly reduced. Overall, these results indicated that ERa might affect mouse embryo cavitation by regulating TE lineage differentiation.

Signaling pathways in mammalian preimplantation development: Linking cellular phenotypes to lineage decisions

“…ERα protein is detected in all the cells at the eight‐cell and morula stages and in the TE cells of blastocysts. In contrast with results from Erα mutant mice, cavitation and TE specification are inhibited in eight‐cell embryos treated with an ERα‐selective antagonist (Cheng et al, ). Conversely, treating embryos with an ERα‐selective agonist promotes cavitation and blastocoel expansion without affecting ICM and TE lineage differentiation, suggesting that maternal contribution might overcome the effects of a lack of ERα in earlier studies.…”

“…Neither Erα nor Erβ knockout is embryonically lethal (Lubahn et al, ; Krege et al, ; Lee et al, ), although ERα mRNA and protein expression is dynamic during early development (Hou and Gorski, ; Hou et al, ; Cheng et al, ). Erα transcripts appear in the zygote and then decline, reappearing in the blastocyst stage.…”

Trophectoderm regeneration to support full-term development in the inner cell mass isolated from bovine blastocyst

“…In addition, to explore the cause of insufficient TE regeneration in mouse embryos, we performed gene expression analysis of 10 primal TE-related genes, Cdx2, Gata2, Gata3, Eomes, Tfap2c, Fgfr1, Esrr␣, Pard6b, Krt8, and Id2, that are critical for TE cell characterization (11,(31)(32)(33)(34)(35)(36)(37)(38) in mouse Whole and re-iICMs using…”

Atypical GATA protein TRPS1 plays indispensable roles in mouse two-cell embryo

“…It was also found to recruit histone deacetylase (HDAC) complexes to enhancers and act as a key repressor of ERα [38], which was dynamically expressed during mouse PED [39][40][41] and affected the expression of MuERV-L at ZGA [42]. Furthermore, through regulating the expression of Gata3, ERα also functions in blastocyst formation [43]. Despite these findings, the possible roles of TRPS1 during PED have not been thoroughly explored.…”