From Hatching into Fetal Life in the Pig

Background: Potential adverse effects of assisted reproductive technologies may have long term consequences on embryonic and fetal development. However, the complex developmental phases occurring after hatching from the zona pellucida are less studied than those occurring before hatching. The aim of the present review is to introduce the major post-hatching developmental features bringing the embryo form the blastocyst into fetal life in the pig. Review: In the pre-hatching mouse blastocyst, the pluripotency of the inner cell mass (ICM) is sustained through expression of OCT4 and NANOG. In the pre-hatching porcine blastocyst, a different and yet unresolved mechanism is operating as OCT4 is expressed in both the ICM and trophectoderm, and NANOG is not expressed at all. Around the time of hatching, OCT4 becomes confined to the ICM. In parallel, the ICM is divided into a ventral cell layer, destined to form the hypoblast, and a dorsal cell mass, destined to form the epiblast. The hypoblast gradually develops into a complete inner lining along the epiblast and the trophectoderm. Upon hatching (around Day 7-8 of gestation), the trophectoderm covering the developing epiblast (Rauber ́s layer) is lost and the embryonic disc is formed by development of a cavity in the epiblast, which subsequently “unfolds” resulting the establishment of the disc. In parallel, the epiblast initiates expression of NANOG in addition to OCT4. The blastocyst enlarges to a sphere of almost 1 cm around Day 10 of gestation. Subsequently, a dramatic elongation of the embryo occurs, and by Day 13 it has formed a thin approximately one meter long filamentous structure. This elongation is paralleled with the initiation of placentation along with which, the embryonic disc undergoes gastrulation. The latter process is preceded by a thickening of the posterior region of the epiblast, putatively developing as a consequence of an absence of inhibitory signals from a condensed portion of the hypoblast underlying the anterior epiblast. The thickened posterior epiblast expresses the primitive streak marker BRACHYURY. Subsequently, the epiblast thickening extends in an anterior direction forming the primitive streak; also expressing BRACHYURY. Gastrulation is hereby initiated, and epiblast cells ingress through the primitive streak to form mesoderm and endoderm; the latter is inserted into the dorsal hypoblast whereas the mesoderm forms a more loosely woven mesenchyme between the epiblast and the endoderm. The anterior mesoderm, ingressing through the anterior end of the primitive streak, referred to as the node, forms the rod-like notochord interposed between the epiblast and the endoderm. During the subsequent neurulation, which is a process overlapping with gastrulation in time, the notochord induces the overlying epiblast to form neural ectoderm, which sequentially develops into the neural plate, neural groove, and neural tube, whereas the lateral epiblast develops into the surface ectoderm. In parallel with the development of the somatic germ layers, ectoderm, mesoderm, and endoderm, the primordial germ cells, the predecessors of the germ line, develop in the posterior epiblast and initiates a migration finally bringing them to the genital ridges of the developing embryo. In parallel, the ectoderm gives rise to the epidermis and neural tissue, the mesoderm develops into the cardiovascular system as well as the urogenital and musculoskeletal systems, whereas the endoderm forms the gastrointestinal system and related organs as the liver and pancreas. Conclusions: Porcine embryonic and fetal development is controlled by molecular mechanisms that to some degree differ from those operating in the mouse. It is of importance to uncover the molecular control of development in ungulates as it has great implications for assisted reproductive technologies as well as for biomedical model research.