Restraint Stress on Female Mice Diminishes the Developmental Potential of Oocytes: Roles of Chromatin Configuration and Histone Modification in Germinal Vesicle Stage Oocytes1

The mechanisms by which restraint stress impairs oocyte developmental potential are unclear. Factors causing differences between the developmental potential of oocytes with surrounded nucleolus (SN) and that of oocytes with nonsurrounded nucleolus (NSN) are not fully characterized. Furthermore, the relationship between increased histone acetylation and methylation and the increased developmental competence in SN oocytes is particularly worth exploring using a system where the SN configuration can be uncoupled (dissociated) from increased histone modifications. In this study, female mice were subjected to restraint for 24 or 48 h or for 23 days before being examined for oocyte chromatin configuration, histone modification, and development in vitro and in vivo. Results showed that restraint for 48 h or 23 days impaired NSN-to-SN transition, histone acetylation and methylation in SN oocytes, and oocyte developmental potential. However, whereas the percentage of stressed SN oocytes returned to normal after a 48-h postrestraint recovery, neither histone acetylation/methylation in SN oocytes nor developmental competence recovered following postrestraint recovery with equine chorionic gonadotropin (eCG) injection. Priming unstressed mice with eCG expedited oocyte histone modification to an early completion. Contrary to the levels of acetylated and methylated histones, the level of phosphorylated H3S10 increased significantly in the stressed SN oocytes. Together, the results suggest that 1) restraint stress impaired oocyte potential with disturbed histone modifications; 2) SN configuration was uncoupled from increased histone acetylation/methylation in the restraint-stressed oocytes; and 3) the developmental potential of SN oocytes is more closely correlated with epigenetic histone modification than with chromatin configuration.