期刊
THERIOGENOLOGY
卷 154, 期 -, 页码 120-127出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.theriogenology.2020.05.019
关键词
Hypoxia; Apoptosis; JNK; FOXO1; Porcine granulosa cells
资金
- National Natural Science Foundation of China [31972571, 31972564, 31630072, 31601939]
- Priority Academic Program Development of Jiangsu Higher Education Institutions [DKQB201903]
- Fundamental Research Funds for the Central Universities [KJQN201705]
- National Major Project for Breeding of Transgenic Pigs [2016ZX08006001-003]
In ovaries, follicles undergo a periodic process of degeneration, namely atresia, during each stage of development. Granulosa cell (GC) apoptosis is believed as the hallmark of follicular atresia. The avascular environment within the granulosa compartment is supposed to cause hypoxic conditions. The effects of hypoxia on organs, tissues, cells can be either positive or negative, depending on the severity and context. The present study aimed to explore whether and how severe hypoxia under in vitro conditions functions in apoptosis of porcine GCs. The current results showed that the apoptosis in porcine GCs exposed to severe hypoxia (1% O-2) was correlated with enhanced activation of c-Jun N-terminal kinase (JNK), nuclear accumulation of FOXO1, as well as elevated level of cleaved caspase-3 and decreased ratio of BCL-2/BAX. Further investigations revealed that severe hypoxia-mediated JNK activation was required for the apoptotic death of porcine GCs and the nuclear transport of FOXO1. Moreover, inhibition of FOXO1 reduced GCs apoptosis upon severe hypoxia exposure. Together, these findings suggested that severe hypoxia might act through JNK/FOXO1 axis to induce apoptosis in porcine GCs. (C) 2020 Elsevier Inc. All rights reserved.
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