Unfolded protein response prevents blastocyst formation during preimplantation embryo development in vitro

Accumulation of unfolded proteins as a result of increased endoplasmic reticulum stress in the developing murine preimplantation embryo in vitro triggers apoptosis and negatively affects blastocyst formation.


Murat Basar, Ph.D., Idil Bozkurt, M.Sc., Ozlem Guzeloglu-Kayisli, Ph.D., Berna Sozen, M.Sc., Isil Tekmen, Ph.D., Frederick Schatz, Ph.D., Aydin Arici, M.D., Charles J. Lockwood, M.D., Umit A. Kayisli, Ph.D.

Volume 102, Issue 6, Pages 1777-1784



To study the effect of increased endoplasmic reticulum (ER) stress as a major nongenomic mechanism for arrested blastocyst development.


Cell and animal study.


The Ohio State University and Yale University.




Pregnant mare serum gonadotropin and hCG were administered IP; two cell embryos were collected 48 hours after hCG administration.

Main Outcome Measure(s):

Blastocyst development rate.


No morphological difference was detected in control versus tunicamycin- (TM) treated embryos until the blastocyst stage. On day 4 of embryonic development, TM treatment reduced blastocyst formation from 79% to 4% and induced nuclear fragmentation. TM treatment caused 2-fold and 2.6-fold increase in binding immunoglobulin protein and spliced-X-box binding protein 1 mRNA expression, respectively. By comparison, the tauroursodeoxycholic acid + TM combination reversed the effect of TM alone on blastocyst formation to near control levels.


These results indicate that increased ER stress during in vitro embryo development triggers an unfolded protein response (UPR) that negatively affects blastocyst formation and suggests that activation of UPR signaling may account for low rates of blastocyst development.

Read the full text at: http://www.fertstert.org/article/S0015-0282(14)02156-6/fulltext

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