Fertilization and Early Embryogenesis: From Research to Clinical Practice

Early embryo development in mammals begins with the recognition and fusion of gametes of both sexes, followed by a series of mitotic cell divisions. The gamete fusion results in the formation of totipotent cells, which are capable of developing into three basic cell lineages in mammals. These include the trophoblast, surrounding the embryo and facilitating communication with the mother, the epiblast which develops into the fetus, and the primitive endoderm which forms the yolk sac. Until implantation, the embryos undergo remarkable changes, including histone modifications, chromatin remodeling, epigenetic modifications of chromatin, the onset of transcription from the embryonic genome, and the first differentiation to the formation of the trilaminar disc, containing all primary cell lineages required for the formation of fetal tissues and organs. Remarkably, some of the most complex events of early development, such as fertilization,
are achieved during complete transcriptional silencing. Another unique feature is how fast the development proceeds. In humans, reaching the stage of early gastrulation takes approximately two weeks.

During the last couple of decades, we have uncovered many mechanisms that play a role during fertilization and early embryonic development. We have better knowledge about molecular players essential for the recognition and fusion of gametes. Thanks to techniques such as live cell imaging, we uncovered what happens to pronuclei after fertilization, and how the first mitotic spindle is built. Sequencing techniques allowed us to analyze chromatin organization within the embryo, and the order of genes as they are transcribed during the awakening of the embryonic genome. Progress in techniques, such as single-cell sequencing, further allowed us to study the cell fate commitment within the embryo.

Although our knowledge has increased significantly, there are still aspects and mechanisms, about which we know very little. Some of them have an impact on the exploitation of germ cells and embryos in human and animal Assisted Reproductive Technology (ART). For example, the protein network facilitates sperm-oocyte fusion or mechanisms of chromosome segregation errors, although they represent the most frequent case of termination of development in mammals. The in vitro culture system of mammalian embryos is still suboptimal, with less than half of embryos reaching the blastocyst stage. Despite the knowledge that the exposure of embryos to in vitro culture likely impacts an individual's health after birth, the optimal conditions to prevent the negative impact are yet to be determined. In summary, the substantial progress made during the last decades uncovered the urgent need for both basic and clinically oriented research in the field of reproduction.

The scope of this Research topic is to present an overview of current progress in reproductive and developmental biology, with specific emphasis on fertilization and early embryonic development. We encourage the submission of various article types including Original Research, Brief Research Reports, and (Mini-)Reviews focusing on but not limited to the following subthemes:

• New discoveries related to basic mechanisms of fertilization and early embryonic development in vertebrates
• Clinical implications arising from research on human or animal germ cells and embryos
• The use of animal models, such as zebrafish, drosophila, c. elegans, etc., to further our understanding of fertilization and basic mechanisms of early embryonic development
• The impact of assisted reproduction technologies (ART) on the development of human embryos
• Determining molecular mechanisms that regulate the quality of preimplantation embryos and developing new approaches to improve the efficiency of ART.