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.

Molecular and Cellular Mechanisms Underlying Preimplantation Embryo Development

“…Blastomere exclusion is one phenomenon that could generate these fragments [33,34]. Recent time-lapse monitoring of embryo development has shown that blastomere exclusion is a common occurrence (64%) [34] Chromosomal analyses of these excluded blastocysts show a higher frequency of aneuploidy which is consistent with the hypothesis that this could be a mechanism of self-correction [33].…”

“…Fragmentation, also known as blebbing, occurs when a portion of an embryo's cell breaks off from the rest of the cell resulting in a membrane-bound cell fragment. Fragmentation may occur as early as the first embryo cell division [33]. Fragmentation is a common occurrence in embryos; however, high levels of fragmentation are associated with embryo loss.…”

“…Fragmentation has been shown to be a dynamic process in that cytoplasmic fragments can be resorbed back into blastomeres. There is considerable variability in the size and cellular and molecular composition of these fragments [33]. Several etiologies of these fragments have been proposed.…”

Increased sperm deoxyribonucleic acid damage leads to poor embryo quality and subfertility of male rats treated with methylphenidate hydrochloride in adolescence

“…It represents a safe and non‐invasive method used by several groups as a parameter to increase pregnancy rates 77 . The high level of fragmentation seen in the embryos sired from the MPH group is consistent with the poor chromatin structure of the sperm 78 . Adverse embryonic kinetics and embryonic genome instability were recently confirmed by single‐cell whole‐genome sequencing of individual blastomeres as a result of DNA fragmentation in bovine sperm caused by gamma‐radiation 79 …”

“…77 The high level of fragmentation seen in the embryos sired from the MPH group is consistent with the poor chromatin structure of the sperm. 78 Adverse embryonic kinetics and embryonic genome instability were recently confirmed by single-cell whole-genome sequencing of individual blastomeres as a result of DNA fragmentation in bovine sperm caused by gamma-radiation. 79 The protocol of treatment used in the present research-5 mg/kg of MPH per kilogram of body weight 80 -is considered within the average dose administered to humans.…”