ZFIN ID: ZDB-PUB-181127-10
Loss-of-function mutations with circadian rhythm regulator Per1/Per2 lead to premature ovarian insufficiency
Zheng, Y., Liu, C., Li, Y., Jiang, H., Yang, P., Tang, J., Xu, Y., Wang, H., He, Y.
Date: 2018
Source: Biology of reproduction   100(4): 1066-1072 (Journal)
Registered Authors: Liu, Chao, Li, Yan, Wang, Han
Keywords: none
MeSH Terms:
  • Animals
  • Circadian Rhythm/genetics
  • Female
  • Infertility, Female/genetics
  • Loss of Function Mutation*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Ovarian Reserve/genetics
  • Period Circadian Proteins/genetics*
  • Primary Ovarian Insufficiency/genetics*
  • Primary Ovarian Insufficiency/pathology
PubMed: 30452546 Full text @ Biol. Reprod.
Mechanism underlying premature ovarian insufficiency remains incompletely understood. Here we report that mice with Per1m/m; Per2m/m double mutations display a decrease in female fertility starting approximately at 20-week-old, with significantly less pups born from 32-week-old onwards. Histological analysis revealed that a significant reduction of ovarian follicles was observed in the Per1/Per2 mutants compared with the littermate controls examined at 26- and 52-week-old while the difference was not statistically significant between the two groups at 3- and 8-week-old. We further showed that vascular development including the ovarian follicle associated vascular growth appeared normal in the Per1/Per2 mutant mice, although clock genes were reported to regulate angiogenesis in zebrafish. The findings imply that loss-of-function mutations with Per1/Per2 result in a premature depletion of ovarian follicle reserve leading to the decline of reproductive capacity.