Blastocoel fluid (BF) harbors embryonic DNA that may result from the marginalization of aneuploid cells during embryogenesis

Abstract

OBJECTIVE: The endoplasmic reticulum (ER) stress is activated in response to an accumulation of unfolded protein in the lumen of the ER. ER stress is critical for cell survival, but chronic or excess ER stress can lead to apoptosis in various cell types. ER stress is known to cause various aging related diseases such as diabetics and neurodegenerative diseases. In this study, the participation of the ER stress in the postovulatory aging of oocyte was examined. DESIGN: Animal model study. MATERIALS AND METHODS: In this study, mouse oocytes released from the oviduct at 12.5 hour and 18.5 hour post-hCG were designated as ‘‘fresh’’ and ‘‘aged’’ oocytes, respectively. Experiments were done as follows: (1) Analysis of expression of BiP (chaperone induced at ER stress) level by western blotting with embryo development in the fresh oocytes, (2) Comparison of expression of BiP at protein level in the fresh and the aged oocytes, (3) Analysis of the effects by ER stress inducer, thapsigargin (Tg: calcium pump inhibitor of ER) on BiP expression and on fertilization rate and embryo development after in vitro fertilization. Animals were treated in accordance with the NIH Guide for the Care and Use of Laboratory Animals, as approved by the Animal Care and Use Committee of Yamagata University. RESULTS: (1) Expression of BiP was the highest in the MII oocytes, and decreased with embryo development after in vitro fertilization. (2) Expression of BiP in the aged oocytes was increased compared with that in the fresh oocytes. (3) Tg treated oocytes showed increase in expression of BiP, low fertilization rate and deteriorated embryo development. Furthermore, Tg treatment in the fresh oocytes deteriorated embryo quality. CONCLUSION: Expression of BiP in mouse oocyte/embryo decreased with the embryo development. The result that excessive expression of BiP in the aged oocyte was observed in association with the poor embryo development suggested that aged oocytes were exposed to excess ER stress. Because excess ER stress induced by Tg leaded low fertilization rate and poor embryo development, these data suggested that ER stress might participate in postovulatory aging process of the mouse oocyte. Supported by: This study was Supported by JSPS KAKEN research grants 20591905 to H.I.