#38 : Maternal Age Affects Morula Compaction and Cell Polarity of Human Embryos

Abstract

Background and Aims: With the exception of chromosome segregation errors, the molecular and biochemical mechanisms responsible for advanced maternal age (AMA)-related reduced embryo developmental competence remain unclear. In women of AMA, the blastocyst formation rate has been reported to decline due to an increase in embryo arrest at the morula stage. Therefore, we aimed to reveal the impact of AMA on cellular events during compaction, as assessed using morphokinetic analysis. We also assessed the possible influence of AMA on the expression of cell polarity markers, yes-associated protein (YAP) and protein kinase C-[Formula: see text] (PKC[Formula: see text]), during blastomere compaction. Method: We retrospectively analysed 2,058 fertilized oocytes, which were stratified by maternal age according to the Society for Assisted Reproductive Technology classification (< 35, 35-37, 38–40, 41–42, and > 42 years). The effects of AMA were assessed in relation to embryo morphokinetics and morphological alterations. Furthermore, 20 voluntarily donated human embryos were used for immunofluorescence staining of YAP and PKC-[Formula: see text]. Results: Delayed embryonic compaction and an increased number of extruded blastomeres post compaction were observed in the > 42-year group. The time interval from the eight-cell stage to compaction initiation was prolonged with increasing age. The number of YAP-positive cells in the outer cells of the morulae was significantly higher in the young age group than in the AMA groups. The PKC[Formula: see text] fluorescence intensity in the cortical region of the morulae was significantly lower in the AMA groups than in the young age groups. Conclusion: Delayed compaction and blastomere extrusion occur more frequently in embryos from women of AMA due to insufficient regulation of cell polarity, which may lead to morula arrest. Further research is required to reveal the impacts of AMA on the mechanism underlying the expression of cell polarity factors and develop methods to avoid AMA-associated morula arrest.