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Peroxiredoxin 4 deficiency induces accelerated ovarian aging through destroyed proteostasis in granulosa cells.
Zou, Xiaofei; Liang, Xiuru; Dai, Wangjuan; Zhu, Ting; Wang, Chaoyi; Zhou, Yutian; Qian, Yi; Yan, Zhengjie; Gao, Chao; Gao, Li; Cui, Yugui; Liu, Jiayin; Meng, Yan.
Afiliación
  • Zou X; State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • Liang X; State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • Dai W; State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • Zhu T; State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • Wang C; State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • Zhou Y; State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • Qian Y; State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • Yan Z; State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • Gao C; State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • Gao L; State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • Cui Y; State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • Liu J; State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
  • Meng Y; State Key Laboratory of Reproductive Medicine and Offspring Health, Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China. Electronic address: ctmengyan@njmu.edu.cn.
Biochim Biophys Acta Mol Basis Dis ; 1870(7): 167334, 2024 10.
Article en En | MEDLINE | ID: mdl-38971505
ABSTRACT
Ovarian aging, a complex and challenging concern within the realm of reproductive medicine, is associated with reduced fertility, menopausal symptoms and long-term health risks. Our previous investigation revealed a correlation between Peroxiredoxin 4 (PRDX4) and human ovarian aging. The purpose of this research was to substantiate the protective role of PRDX4 against ovarian aging and elucidate the underlying molecular mechanism in mice. In this study, a Prdx4-/- mouse model was established and it was observed that the deficiency of PRDX4 led to only an accelerated decline of ovarian function in comparison to wild-type (WT) mice. The impaired ovarian function observed in this study can be attributed to an imbalance in protein homeostasis, an exacerbation of endoplasmic reticulum stress (ER stress), and ultimately an increase in apoptosis of granulosa cells. Furthermore, our research reveals a noteworthy decline in the expression of Follicle-stimulating hormone receptor (FSHR) in aging Prdx4-/- mice, especially the functional trimer, due to impaired disulfide bond formation. Contrarily, the overexpression of PRDX4 facilitated the maintenance of protein homeostasis, mitigated ER stress, and consequently elevated E2 levels in a simulated KGN cell aging model. Additionally, the overexpression of PRDX4 restored the expression of the correct spatial conformation of FSHR, the functional trimer. In summary, our research reveals the significant contribution of PRDX4 in delaying ovarian aging, presenting a novel and promising therapeutic target for ovarian aging from the perspective of endoplasmic reticulum protein homeostasis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ovario / Envejecimiento / Ratones Noqueados / Peroxirredoxinas / Estrés del Retículo Endoplásmico / Proteostasis / Células de la Granulosa Límite: Animals / Female / Humans Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ovario / Envejecimiento / Ratones Noqueados / Peroxirredoxinas / Estrés del Retículo Endoplásmico / Proteostasis / Células de la Granulosa Límite: Animals / Female / Humans Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos