ID3 regulates progesterone synthesis in bovine cumulus cells through modulation of mitochondrial function

DNA binding inhibitory factor 3 (ID3) has been shown to have a key role in maintaining proliferation and differentiation. It has been suggested that ID3 may also affect mammalian ovarian function. However, the specific roles and mechanisms are unclear. In this study, the expression level of ID3 in cumulus cells (CCs) was inhibited by siRNA, and the downstream regulatory network of ID3 was uncovered by high -throughput sequencing. The effects of ID3 inhibition on mitochondrial function, progesterone synthe-sis, and oocyte maturation were further explored. The GO and KEGG analysis results showed that after ID3 inhibition, differentially expressed genes, including StAR, CYP11A1, and HSD3B1, were involved in cholesterol-related processes and progesterone-mediated oocyte maturation. Apoptosis in CC was increased, while the phosphorylation level of ERK1/2 was inhibited. During this process, mitochondrial dynamics and function were disrupted. In addition, the first polar body extrusion rate, ATP production and antioxidation capacity were reduced, which suggested that ID3 inhibition led to poor oocyte maturation and quality. The results will provide a new basis for understanding the biological roles of ID3 as well as cumulus cells.& COPY; 2023 Published by Elsevier Inc.

Automated summary

This study investigated the effects of inhibiting the expression of ID3 on cumulus cells (CCs) and uncovered the downstream regulatory network of ID3. The results showed that ID3 inhibition disrupted mitochondrial function, progesterone synthesis, and oocyte maturation. GO and KEGG analysis revealed the involvement of cholesterol-related processes and progesterone-mediated oocyte maturation. The study also found that ID3 inhibition led to increased apoptosis, inhibited phosphorylation of ERK1/2, and disrupted mitochondrial dynamics and function, resulting in poor oocyte maturation and quality. These findings contribute to the understanding of the biological roles of ID3 and cumulus cells.