Stresses on Female Mice Impair Oocyte Developmental Potential: Effects of Stress Severity and Duration on Oocytes at the Growing Follicle Stage

Reprod Sci. 2016 Sep;23(9):1148-57. doi: 10.1177/1933719116630416. Epub 2016 Feb 14.


Aim: Although previous studies found that 1-time acute stress applied during follicle maturation impaired oocyte competence, it is unknown whether repeated chronic stress, which is known to cause animal behavioral adaptation, would damage oocytes when applied during follicle growth.

Methods and results: In this study, female mice were exposed to repeated restraint stress (RRS) or unpredictable stress (UPS) for different days before equine chorionic gonadotropin injection to initiate oocyte prematuration development and to observe effects of different stressors on oocytes in the growing follicles. The results showed that although oocyte pre- and postimplantation development was unaffected when mice were exposed to RRS or UPS once a day for 4 days, development was impaired when mice were exposed to RRS for 8 or more days or to UPS twice a day for 4 days (4 × 2). The 4 × 2 UPS caused more oxidative stress in oocytes and severer apoptosis in antral follicles than did the 4-day RRS. The RRS mice were stressed consistently from days 1 to 23 of restraint, and the stress that a mouse had 4 × 2 UPS was severer than that from 4-day RRS.

Conclusion: The results suggest that (1) the degree that a stress damages oocytes is the product of duration × severity of the stress; (2) RRS impaired oocyte developmental potential through cumulative effects on growing follicles; and (3) preantral follicles were not as sensitive to stress as antral follicles were.

Keywords: mice; oocyte; ovarian follicles; repeated restraint stress; unpredictable stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / etiology
  • Anxiety / physiopathology
  • Apoptosis
  • Body Weight
  • Female
  • Glucocorticoids / blood
  • Glutathione / metabolism
  • Hydrocortisone / blood
  • Mice
  • Oocytes / metabolism
  • Oocytes / physiology*
  • Ovarian Follicle / growth & development*
  • Ovarian Follicle / physiopathology*
  • Restraint, Physical
  • Stress, Psychological / complications
  • Stress, Psychological / physiopathology*


  • Glucocorticoids
  • Glutathione
  • Hydrocortisone