Chronic restraint stress induces excessive activation of primordial follicles in mice ovaries

• Published in: PloS one 2018-03, Vol.13 (3), p.e0194894-e0194894
• Main Authors: Xu, Minhua, Sun, Junyan, Wang, Qian, Zhang, Qiuwan, Wei, Chunsheng, Lai, Dongmei
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Activation; AKT protein; Biology and Life Sciences; Childrens health; Chromosome 10; Complications and side effects; Corticotropin-releasing hormone; Endocrinology; Females; Follicles; Genetic aspects; Homology; Hospitals; Kinases; Laboratory animals; Medicine; Medicine and Health Sciences; mRNA; Ovaries; Ovulation; Physiological aspects; Polymerase chain reaction; Psychological aspects; PTEN protein; Reproduction; Research and Analysis Methods; Rodents; Signaling; Social Sciences; Stress (Psychology); Stresses; Studies; Tensin
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0194894

Chronic stress is an important factor influencing people's health. It usually causes endocrinal disorders and a decline in reproduction in females. Although studies of both human and animals suggest a detrimental effect of stress on reproduction, the influence of chronic stress on the ovarian reservation and follicular development is still not clear. In this study, a chronic restraint stress (CRS) mouse model was used to investigate the effect of stress on ovarian reservation and follicular development and explore the underlying mechanism. In this study, after 8 weeks of CRS, primordial follicles were excessively activated in the ovaries of the CRS group compared with the control group. Further results showed that the activation of primordial follicles induced by CRS was involved in the increasing expression level of Kit ligand and its receptor Kit and the activation of phosphatidylinositol 3-kinase (PI3K)/phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/protein kinase B (Akt) pathway. The corticotropin-releasing hormone (CRH) is a neuropeptide released due to stress, which plays an important role in regulating follicle development. A high level of serum CRH was detected in the CRS mouse model, and the real-time polymerase chain reaction assay showed that the mRNA level of its main receptor CRHR1increased in the ovaries of the CRS mouse group. Moreover, 100nM CRH significantly improved the activation of primordial follicles in newborn mouse ovaries in vitro. These results demonstrated that CRS could induce immoderate activation of primordial follicles accompanied by the activation of Kit-PI3K signaling, in which CRH might be an important endocrine factor.