Abnormal early folliculogenesis due to impeded pyruvate metabolism in mouse oocytes.
Biol Reprod
; 105(1): 64-75, 2021 07 02.
Article
en En
| MEDLINE
| ID: mdl-33824958
ABSTRACT
Fetal ovarian germ cells show characteristic energy metabolism status, such as enhanced mitochondrial metabolism as well as glycolysis, but their roles in early folliculogenesis are unclear. We show here that inhibition of pyruvate uptake to mitochondria by UK5099 in organ cultures of fetal mouse ovaries resulted in repressed early folliculogenesis without affecting energy production, survival of oocytes, or meiosis. In addition, the abnormal folliculogenesis by UK5099 was partially rescued by α-ketoglutarate and succinate, intermediate metabolites in the TCA cycle, suggesting the importance of those metabolites. The expression of TGFß-related genes Gdf9 and Bmp15 in ovarian germ cells, which are crucial for folliculogenesis, was downregulated by UK5099, and the addition of recombinant GDF9 partially rescued the abnormal folliculogenesis induced by UK5099. We also found that early folliculogenesis was similarly repressed, as in the culture, in the ovaries of a germ cell-specific knockout of Mpc2, which encodes a mitochondria pyruvate carrier that is targeted by UK5099. These results suggest that insufficient Gdf9 expression induced by abnormal pyruvate metabolism in oocytes results in early follicular dysgenesis, which is a possible cause of defective folliculogenesis in humans.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Oocitos
/
Acrilatos
/
Ácido Pirúvico
/
Proteína Morfogenética Ósea 15
/
Factor 9 de Diferenciación de Crecimiento
/
Folículo Ovárico
Límite:
Animals
Idioma:
En
Revista:
Biol Reprod
Año:
2021
Tipo del documento:
Article
País de afiliación:
Japón