Cellular and Molecular Nature of Fragmentation of Human Embryos

Abstract

Embryo fragmentation represents a phenomenon generally characterized by the presence of membrane-bound extracellular cytoplasm into the perivitelline space. Recent evidence supports the cellular and molecular heterogeneity of embryo fragments. In this narrative review, we described the different embryo fragment-like cellular structures in their morphology, molecular content, and supposed function and have reported the proposed theories on their origin over the years. We identified articles related to characterization of embryo fragmentation with a specific literature search string. The occurrence of embryo fragmentation has been related to various mechanisms, of which the most studied are apoptotic cell death, membrane compartmentalization of altered DNA, cytoskeletal disorders, and vesicle formation. These phenomena are thought to result in the extrusion of entire blastomeres, release of apoptotic bodies and other vesicles, and micronuclei formation. Different patterns of fragmentation may have different etiologies and effects on embryo competence. Removal of fragments from the embryo before embryo transfer with the aim to improve implantation potential should be reconsidered on the basis of the present observations.

Keywords: apoptosis; embryo; fragmentation; micronuclei; vesicles.

Figure 1

Schematic representation of the various fragment-like cellular structures detected in embryos.

Figure 2

Different degrees of fragmentation in cleavage stage human embryos. (A–F) Representative images of day 3 embryos characterized by cellular fragments of different sizes and positions. For each embryo, arrows indicate a representative cellular fragment.

Figure 3

Cellular debris/fragments in the zona pellucida of day 5, 6, and 7 blastocysts. For each embryo, arrows indicate a representative cellular fragment or blastomere excluded upon blastocyst formation. (A–D) Representative images of collapsing blastocysts presenting different degree of fragmentation; (E) hatching blastocyst characterized by several cellular fragments within the zona pellucida; (F) hatched blastocyst on the right and its original zona pellucida containing leftovers of cell debris on the left.

Figure 4

Entire blastomeres are excluded upon blastocyst formation. (A–F) Representative images of expanded blastocysts expelling one or more cells.