Biol Reprod. 2018 Nov 18. doi: 10.1093/biolre/ioy245. [Epub ahead of print]
Zheng Y1, Liu C1, Li Y1, Jiang H1, Yang P2, Tang J3, Xu Y4, Wang H5, He Y1.
Author Information
1Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, China.
2Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, USA.
3Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
4Cam-Su Genomic Resources Center, Soochow University, Suzhou, China.
5Center for Circadian Clocks, Soochow University, Suzhou, China.
Abstract
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.