Dual role of NR4A1 in porcine ovarian granulosa cell differentiation and granulosa-lutein cell regression in vitro.
Theriogenology
; 198: 292-304, 2023 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-36634443
ABSTRACT
This study aimed to investigate the role of NR4A1 in forskolin (FSK)-induced granulosa cell (GC) differentiation and PGF2α-induced granulosa-lutein cell (GLC) regression. For experiment 1, primary porcine GCs were pre-cultured for 6 d before induced-differentiation by FSK with or without siNR4A1, and changes in GC proliferation, lipid droplets (LDs), and P4 level were detected. For experiment 2, the GLC model was established by FSK as in experiment 1, and then PGF2α was utilized to induce GLC regression with or without siNR4A1, changes in P4 secretion, apoptosis proteins, and associated signaling pathway members were detected. Results showed that in experiment 1, FSK up-regulated NR4A1 expression during GC differentiation and decreased GC proliferation activity, which was reversed by siNR4A1. siNR4A1 inhibited the FSK-induced decreases in Cyclin B1/D1 and CDK1/2 mRNA abundances, and increases in P21/P27 mRNA abundances, and FSK-induced LD accumulation. FSK up-regulated P4 secretion and StAR, CYP11A1 and HSD3B expression, decreased CYP19A1 expression, which were reversed by siNR4A1 except for StAR expression. In experiment 2, PGF2α induced NR4A1 expression and reduced GLC viability, which were reversed by siNR4A1. Compared with PGF2α group, the levels of P4 secretion and StAR expression were higher in PGF2α+siNR4A1 group, while CYP11A1 and HSD3B expressions held at low levels. siNR4A1 inhibited PGF2α-induced expression of apoptosis proteins (caspase3, Bax, Fas, TNFa), ATF3, and phosphorylated MAPKs (ERK1/2, P38, JNK). In summary, NR4A1 is involved in regulating porcine GC differentiation and GLC regression as well as the changes in cell proliferation, apoptosis, steroidogenesis, and MAPK pathways, which provide a theoretical basis for further understanding of the mechanism of porcine luteal formation and regression.
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Base de dados:
MEDLINE
Assunto principal:
Células Lúteas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article