Effect of Maternal Age on Hippo Pathway Related Gene Expressions and Protein Localization Pattern in Human Embryos (Pages: 74-80)

Sahar Gharanfoli , Abdolhoseein Shahverdi , Azam Dalman , Pooneh Ghaznavi , Hiva Alipour , Poopak Eftekhari-Yazdi *,


The Hippo pathway plays an important role in embryo development, and separation of the trophectoderm (TE) and inner cell mass (ICM) cell lines. Therefore, this study investigated the effect of maternal age on the activity of this pathway in human embryos.


In this experimental study, Embryos that developed up to the blastocyst stage, and embryos whose growth stopped at the morula stage, were collected from women aged 20-30 years (young group, 94 embryos), and >37 years (old group, 89 embryos). The expression of OCT4, SOX2, CDX2, GATA3, YAP (as Hippo propagation markers) genes and proteins, in both groups were evaluated using qRT-PCR and immunofluorescence methods.


There was no significant difference in the expression of OCT4, SOX2, CDX2, GATA3 and YAP genes in blastocyst and morula stage between the two groups. However, SOX2 and CDX2 gene expression in morula stage embryos of the old group was statistically lower than that of the young group (P=0.007 and P=0.008 respectively). Additionally, in embryos collected from women > 37 years, at the blastocyst stage, P-YAP protein was found to be accumulated in the TE, but it almost disappeared from the inner cell mass ICM. Also, in the old group, YAP protein expression, contrary to expectation, was expressed in the ICM rather than TE, was expressed in the ICM rather than TE.


The results of this study show that the YAP and P-YAP of Hippo signalling pathway may be altered by increasing age.