Blastocyst activation engenders transcriptome reprogram affecting X-chromosome reactivation and inflammatory trigger of implantation

Abstract

Implantation of the blastocyst into the uterus is the gateway for further embryonic development in mammals. Programming of blastocyst to an implantation-competent state known as blastocyst activation is the determining factor for implantation into the receptive uterus. However, it remains largely unclear how the blastocyst is globally programmed for implantation. Employing a delayed implantation mouse model, we show here that the blastocyst undergoes extensive programming essential for implantation. By analyzing the transcriptional profile of blastocysts with different implantation competency, we reveal the dynamic change in the biosynthesis, metabolism, and proliferation during blastocyst reactivation from diapause. We also demonstrate that reactivation of the X chromosome, one of the most important events during periimplantation of female embryonic development, is not completed even in blastocysts under conditions of dormancy, despite long term suspension in the uterus. Moreover, the mural trophectoderm (TE), but not the polar TE, differentiates to be more invasive through the weakened cell-cell tight junctions and extracellular matrices (ECMs). By analyzing the differentially expressed profile of secretory proteins, we further demonstrate that the blastocyst functions as a proinflammatory body to secrete proinflammatory signals, such as TNFα and S100A9, thereby triggering embryo-uterine attachment reaction during implantation. Collectively, our data systematically and comprehensively disclose the programming of blastocyst reactivation from diapause for implantation and uncover previously undefined roles of blastocyst during implantation.

microRNAs Regulating Human and Mouse Naïve Pluripotency

“…Importantly, we propose that the dynamics of the paused stage, embryonic diapause are affected by microRNA regulated stress and inflammation response genes. This is interesting in the light of recent publications that have revealed importance of stress response and inflammation in regulation of embryonic diapause and stem cell quiescence [35,88,89], and calls for further analysis on microRNA contribution in stress induced regulation of pause in development.…”

In Vitro Derivation of Quiescent Mouse Embryonic Stem Cells Based on Distinct Mitochondrial Activity

“…Diapaused embryos can resume their normal development in response to favorable environments ( He et al., 2019 ; Renfree and Fenelon, 2017 ). To determine whether quiescent ESCs are capable of responding to distinct environmental cues, we analyze their behaviors under self-renewal and differentiation conditions.…”

Single Cell Proteomics Profiling Revealing that Embryo Secreted TNF-α play Critical Role during Embryo Implantation to Endometrium

“…In each well of a 96-well plate, 1x10 4 Ishikawa cells were cultured as attached monolayers overnight. Then different dosage of TNF-α (R&D, Minneapolis, MN, USA) and ETA were used to treat the cell line.…”

“…Using mice embryo activation model, Wang et al has found that several cytokines, including TNF-α, is activated when embryo form dominancy to the activated status and play roles in Xchromosome reactivation. 4 Therefore, dysregulation of these factors would potentially cause the skewed cross-talk of embryo and endometrium, which could lead to implantation failure in clinic.…”