Translational Comparison of the Human and Mouse Yolk Sac Development and Function

The yolk sac (YS) is the oldest of the extraembryonic membranes in vertebrates. Considered a transitory structure in the human species, the importance of the YS for a successful pregnancy is often overlooked. Due to the general inaccessibility of healthy human YS tissue for research, the use of experimental animal models is of great value. In order to better understand whether the mouse could be used as a translational model for the study of the human YS under normal and pathological conditions, this review comprehensively describes key developmental aspects of the human and mouse YS, detailing their development and function. YS major similarities in both species comprise the following: (1) histological composition (both being composed of endoderm, mesoderm, and mesothelium layers); (2) endoderm endocytosis, synthesis, secretion, and transport capabilities; and (3) mesoderm onset of haematopoiesis and angiogenesis. Examples of main dissimilarities include (1) persistence across pregnancy (i.e. early pregnancy in humans vs term pregnancy in mice); (2) the existence of a secondary YS in humans; (3) the presence of proliferative primordial germ cells (PGCs) in the human versus their absence in mice; and (4) eversion of histological layers in the mouse. Although these differences should be considered when interpreting data from mouse-based studies, the overall morphofunctional similarities in the YS between these species indicate that the mouse can be potentially used as a translational model for the study of the human YS.