Molecular Drivers of Developmental Arrest in the Human Preimplantation Embryo: A Systematic Review and Critical Analysis Leading to Mapping Future Research

Abstract

Developmental arrest of the preimplantation embryo is a multifactorial condition, characterized by lack of cellular division for at least 24 hours, hindering the in vitro fertilization cycle outcome. This systematic review aims to present the molecular drivers of developmental arrest, focusing on embryonic and parental factors. A systematic search in PubMed/Medline, Embase and Cochrane-Central-Database was performed in January 2021. A total of 76 studies were included. The identified embryonic factors associated with arrest included gene variations, mitochondrial DNA copy number, methylation patterns, chromosomal abnormalities, metabolic profile and morphological features. Parental factors included, gene variation, protein expression levels and infertility etiology. A valuable conclusion emerging through critical analysis indicated that genetic origins of developmental arrest analyzed from the perspective of parental infertility etiology and the embryo itself, share common ground. This is a unique and long-overdue contribution to literature that for the first time presents an all-inclusive methodological report on the molecular drivers leading to preimplantation embryos’ arrested development. The variety and heterogeneity of developmental arrest drivers, along with their inevitable intertwining relationships does not allow for prioritization on the factors playing a more definitive role in arrested development. This systematic review provides the basis for further research in the field.

Arginine Regulates Zygotic Genome Activation in Porcine Embryos Under Nutrition Restriction

“…Therefore, we removed nutrients from the medium such that the embryos could develop to the 4-cell stage using maternally derived substances, but development was arrested thereafter. Abnormal ZGA is one of the main causes of early embryonic developmental arrest in mammals ( 62 , 63 ). The time of mammalian developmental arrest is consistent with the time of ZGA, and developmental arrest in pigs occurs at the 4-cell stage ( 64 ).…”

Desiccated cat spermatozoa retain DNA integrity and developmental potential after prolonged storage and shipping at non-cryogenic temperatures

“…While it is generally believed that the underlying cause is originating from the oocyte and can be partially circumvented through culture environmental changes [49,50], our results hinted possible involvement of paternal factors in this process. Paternal factors, other than sperm chromatin, that have been proposed to contribute to post-fertilization events include centrosomes, sperm RNAs, microRNAs, and sperm epigenome [51][52][53][54][55]. Future studies will be required to investigate the influence of desiccation and storage on sperm centrosome, transcripts, and epigenome.…”

Molecular Clues to Understanding Causes of Human-Assisted Reproduction Treatment Failures and Possible Treatment Options

“…Even though oocyte aneuploidies are responsible for most ART failures, especially in women of advanced age, other oocyte-borne ART failures are caused by specific gene variations, methylation pattern abnormalities, and inadequate gene expression levels (reviewed in Sfakianoudis et al [ 34 ]).…”

“…However, it is rarely responsible for oocyte quality. The quality of oocytes is mainly dependent on the female age, and it can be ameliorated, to some extent, by medical treatments in most cases [ 34 ].…”

“…Embryonic development is particularly sensitive to differential expression or mutation of numerous genes that control the pathways involved in cell cycle regulation, DNA repair and oocyte cytoplasmic maturation [ 34 ].…”