Uterine receptivity, embryo attachment, and embryo invasion: Multistep processes in embryo implantation

Abstract

Background Recurrent implantation failure is a critical issue in IVF‐ET treatment. Successful embryo implantation needs appropriate molecular and cellular communications between embryo and uterus. Rodent models have been used intensively to understand these mechanisms. Methods The molecular and cellular mechanisms of embryo implantation were described by referring to the previous literature investigated by us and others. The studies using mouse models of embryo implantation were mainly cited. Results Progesterone (P4) produced by ovarian corpus luteum provides the uterus with receptivity to the embryo, and uterine epithelial growth arrest and stromal proliferation, what we call uterine proliferation‐differentiation switching (PDS), take place in the peri‐implantation period before embryo attachment. Uterine PDS is a hallmark of uterine receptivity, and several genes such as HAND2 and BMI1, control uterine PDS by modulating P4‐PR signaling. As the next implantation process, embryo attachment onto the luminal epithelium occurs. This process is regulated by FOXA2‐LIF pathway and planar cell polarity signaling. Then, the luminal epithelium at the embryo attachment site detaches from the stroma, which enables trophoblast invasion. This process of embryo invasion is regulated by HIF2α in the stroma. Conclusion These findings indicate that embryo implantation contains multistep processes regulated by specific molecular pathways.

Promoting Roles of Embryonic Signals in Embryo Implantation and Placentation in Cooperation with Endocrine and Immune Systems

“…Estrogen is mainly secreted from growing follicles and progesterone is produced by the corpus luteum, a newly formed endocrine organ originating from the ovulated follicle. This sequential endocrine stimulation is closely coordinated with the estrus cycle, creating the endometrial receptive phase, referred to as an implantation window [3][4][5][6].…”

Computational modelling unveils how epiblast remodelling and positioning rely on trophectoderm morphogenesis during mouse implantation

“…Understanding the processes by which the mammalian embryo implants in the maternal uterus is crucial to many breakthroughs in embryology [1]. New insights into these morphogenesis events could be of great importance in helping for example to reduce human infertility [31]. Although advances have been made by studying biochemical cues involved in these events, we focused here on the mechanical basis at the cellular level of epiblast morphogenesis.…”

Comparative secretome profile analysis of cultured immortalized human endometrial stromal cells supplemented with implanted versus nonimplanted blastocyst‐conditioned medium: A preliminary analysis

“…3), which were reported to be involved in the process of embryo implantation in previous studies. 7,34 Therefore, the signals in BCM could trigger endometrial cells like HESCs to prepare for implantation. The physiological factors for interaction may present as specific cytokine secretions, as determined in our study.…”