Making the blastocyst: lessons from the mouse

Abstract

Mammalian preimplantation development, which is the period extending from fertilization to implantation, results in the formation of a blastocyst with three distinct cell lineages. Only one of these lineages, the epiblast, contributes to the embryo itself, while the other two lineages, the trophectoderm and the primitive endoderm, become extraembryonic tissues. Significant gains have been made in our understanding of the major events of mouse preimplantation development, and recent discoveries have shed new light on the establishment of the three blastocyst lineages. What is less clear, however, is how closely human preimplantation development mimics that in the mouse. A greater understanding of the similarities and differences between mouse and human preimplantation development has implications for improving assisted reproductive technologies and for deriving human embryonic stem cells. IntroductionThe period of preimplantation development in mammals, extending from egg fertilization to implantation of the blastocyst in the uterus, is a key stage during which the first three major cell lineages of the embryo and its extraembryonic membranes are set aside. These three lineages contribute to distinct tissues in later development: the epiblast (EPI) gives rise to the fetus itself; the trophectoderm (TE) goes on to form the majority of the fetal contribution to the placenta; and the primitive endoderm (PE) becomes the parietal and visceral endoderm, which later contributes to the yolk sac. Knowledge about how these lineages develop during the preimplantation period has major clinical implications for increasing the success of assisted reproductive strategies (ARTs) such as in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD), preventing the high rate of early pregnancy loss in humans, and improving the derivation of stem cell lines from human embryos.Much of what we know about preimplantation development has come from studies in the mouse, which has been used as a model for the early human embryo for over 40 years. Here, we review what has been learned from the mouse about the major events of mammalian preimplantation development and discuss recent work that has shed new insight on how the three blastocyst lineages come to be established. Despite the significant progress that has been made, we still know little about how closely the events of preimplantation development in the mouse reflect the human situation. We compare between mouse and human development where possible and point out where more investigation of early human development could be especially worthwhile.

Notch1 controls development of the extravillous trophoblast lineage in the human placenta

“…Critical regulators controlling trophoblast stemness and lineage determination have been vastly studied in developing mice (45)(46)(47)(48). However, data on key factors controlling human placental development are scarce.…”

Mouse pluripotent stem cells at a glance

“…This totipotent state is maintained from the zygote stage until the early blastocyst (or late cleavage) stage (Tarkowski et al, 2010). Thereafter, cells gradually lose their developmental potency and undergo functional specialisation (reviewed in Cockburn and Rossant, 2010;Surani et al, 2007). When the morula stage is reached, the cells form a compact sphere containing two different cell layers.…”

Binding of FGF2 to FGFR2 in an autocrine mode in trophectoderm cells is indispensable for mouse blastocyst formation through PKC-p38 pathway

“…The information of the antibodies used is given in Table 1. The embryos were maintained in culture in 5% CO 2 and atmospheric air at 37 C. After 24 h of treatment, all embryos from each group were imaged at time point equivalent to 113 h post-hCG injection. The diameter of the embryos was used to assess blastocyst expansion.…”

“…The EPI will give rise to the embryo proper, the PrE forms some of the extraembryonic membranes, and the TE contributes to the placenta. 2,3 Functional tight junctions form a seal between the cells of the TE, which is essential for fluid accumulation and formation of the blastocyst cavity. 4,5 The Na-K ATPase is also a critical mediator of blastocyst formation as it establishes a transtrophectoderm ionic gradient that directs fluid movement across the epithelium of the TE.…”