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GRIM19 deficiency aggravates metabolic disorder and ovarian dysfunction in PCOS.
Yang, Lin; Yang, Yang; Han, Xiaojuan; Huang, Chengzi; Wang, Ying; Jiang, Danni; Chao, Lan.
Afiliación
  • Yang L; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, PR China.
  • Yang Y; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, PR China.
  • Han X; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, PR China.
  • Huang C; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, PR China.
  • Wang Y; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, PR China.
  • Jiang D; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, PR China.
  • Chao L; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, PR China. Electronic address: chaolan@email.sdu.edu.cn.
Biochim Biophys Acta Mol Basis Dis ; 1870(4): 167063, 2024 04.
Article en En | MEDLINE | ID: mdl-38360073
ABSTRACT
CONTEXT Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. Retinoid-interferon-induced mortality 19 (GRIM19) is a functional component of mitochondrial complex I that plays a role in cellular energy metabolism. However, the role of GRIM19 in the pathogenesis of PCOS is still unclear.

OBJECTIVE:

To investigate the role of GRIM19 in the pathogenesis of PCOS.

DESIGN:

We first measured the expression of GRIM19 in human granulosa cells (hGCs) from patients with and without PCOS (n = 16 per group), and then established a PCOS mouse model with WT and Grim19+/- mice for in vivo experiments. Glucose uptake-related genes RAC1 and GLUT4 and energy metabolism levels in KGN cells were examined in vitro by knocking down GRIM19 in the cell lines. Additionally, ovulation-related genes such as p-ERK1/2, HAS2, and PTX3 were also studied to determine their expression levels.

RESULTS:

GRIM19 expression was reduced in hGCs of PCOS patients, which was negatively correlated with BMI and serum testosterone level. Grim19+/- mice with PCOS exhibited a markedly anovulatory phenotype and disturbed glycolipid metabolism. In vitro experiments, GRIM19 deficiency inhibited the RAC1/GLUT4 pathway, reducing insulin-stimulated glucose uptake in KGN cells. Moreover, GRIM19 deficiency induced mitochondrial dysfunction, defective glucose metabolism, and apoptosis. In addition, GRIM19 deficiency suppressed the expression of ovulation-related genes in KGN cells, which was regulated by dihydrotestosterone mediated androgen receptor.

CONCLUSIONS:

GRIM19 deficiency may mediate ovulation and glucose metabolism disorders in PCOS patients. Our results suggest that GRIM19 may be a new target for diagnosis and treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome del Ovario Poliquístico / Enfermedades Metabólicas Límite: Animals / Female / Humans Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome del Ovario Poliquístico / Enfermedades Metabólicas Límite: Animals / Female / Humans Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos