@Article{biocell.2023.045884,
AUTHOR = {DAOLUN YU, DEYONG SHE, KAI GE, LEI YANG, RUINA ZHAN, SHAN LU, YAFEI CAI},
TITLE = {<i>Smad8</i> is involvement in follicular development via the regulation of granulosa cell growth and steroidogenesis in mice},
JOURNAL = {BIOCELL},
VOLUME = {48},
YEAR = {2024},
NUMBER = {1},
PAGES = {139--147},
URL = {http://www.techscience.com/biocell/v48n1/55441},
ISSN = {1667-5746},
ABSTRACT = { <b>Background:</b> SMAD family proteins (SMADs) are crucial transcription factors downstream of transforming growth factor beta (TGF-ß)/SMAD signaling pathways that have been reported to play a pivotal role in mammalian reproduction. However, the role of SMAD family member 8 (SMAD8, also known as SMAD9), a member of the SMAD family, in mammalian reproduction remains unclear. <b>Methods:</b> We employed RNA interference techniques to knock down <i>Smad8</i> expression in mouse granulosa cells (GCs) to investigate the effects of <i>Smad8</i> on GC growth and steroidogenesis. <b>Results:</b> Our findings revealed a significant decrease in the proliferative capacity and a substantial increase in the apoptosis rate of GCs after transfection with <i>Smad8</i>-siRNA for 48 h. Subsequent hormone assays demonstrated a significant decrease in estradiol (E<sub>2</sub>) levels, whereas progesterone (P<sub>4</sub>) remained unchanged. Further mechanistic analysis showed that the mRNA expression of proliferating cell nuclear antigen (<i>Pcna</i>), <i>Cyclin D2</i>, cell cycle-dependent kinase 4 (<i>Cdk4</i>), B-cell lymphoma-2 (<i>Bcl-2</i>), estrogen receptor (<i>Er</i>), luteinizing hormone receptor (<i>Lhr</i>) and cytochrome P450 family 19 subfamily A member 1 (<i>Cyp19a1</i>) significantly decreased. Conversely, the mRNA of cysteine aspartate proteinase 3 (<i>Caspase 3</i>) significantly increased, wheras <i>Bcl2</i>-associated X (<i>Bax</i>), follicle-stimulating hormone receptor (<i>Fshr</i>) and cytochrome P450 family 11 subfamily A member 1 (<i>Cyp11a1</i>) remained unchanged compared to the controls. <b>Conclusion:</b> This study indicates that <i>Smad8</i> knockdown inhibits cell proliferation, promotes apoptosis, reduces <i>Er</i> and <i>Lhr</i> transcription, and decreases E<sub>2</sub> production in mouse GCs. These findings suggest that <i>Smad8</i> may serve as a novel genetic marker for mammalian reproduction.},
DOI = {10.32604/biocell.2023.045884}
}