Granulosa cell-specific FOXJ2 overexpression induces premature ovarian insufficiency by triggering apoptosis via mitochondrial calcium overload
FOXJ2 overexpression in GCs led to reduced fertility, hormonal abnormalities, and follicle atresia, starting at the initiation of sexual maturity, resulting in a premature ovarian insufficiency (POI)-like phenotype. Increased apoptosis and mitochondrial calcium overload were detected in the GCs of Amh-cre; Foxj2<sup>tg/tg</sup> mice. Mcu (encoding a mitochondrial calcium uniporter) was observed to be upregulated in the GCs of the Amh-cre; Foxj2<sup>tg/tg</sup> mice and was a direct target of FOXJ2. Moreover, Mcu knockdown restored mitochondrial calcium homeostasis and reduced the apoptosis in the GCs of the Amh-cre; Foxj2<sup>tg/tg</sup> mice and in KGN cells transfected with FOXJ2-overexpression lentivirus.
Authors
- Furong Bai (ORCID: https://orcid.org/0000-0002-5312-5021)
- Bufang Xu (ORCID: https://orcid.org/0000-0002-1386-7119)
- Yujie Tang (ORCID: https://orcid.org/0000-0001-7647-5780)
- Yunxia Zhang (ORCID: https://orcid.org/0000-0002-5637-6782)
- Qiqian Wu
- Yanqin Hu (ORCID: https://orcid.org/0000-0002-6156-8471)
- Jingwen Wu (ORCID: https://orcid.org/0000-0003-0939-511X)
Institutions
- Shanghai Jiao Tong University (CN)
Publication Details
- Journal
- Journal of Ovarian Research
- Published
- 2025-04-09
- DOI
- https://doi.org/10.1186/s13048-025-01651-0
- Citations
- 6
- Primary Topic
- Genetics, Aging, and Longevity in Model Organisms
- Type
- article
- Field-Weighted Citation Impact
- 5.72
Funders
- National Science Foundation
- Shanghai Municipal Health Commission
- National Natural Science Foundation of China
- Shanghai Municipal Health and Family Planning Commission