Pyruvate Regulates the Expression of DLAT to Promote Follicular Growth

Increasing evidence has suggested that dihydrolipoamide S-acetyltransferase (<i>DLAT</i>), a subunit of the pyruvate dehydrogenase complex, is crucial for pyruvate metabolism and the regulation of cell death. The excessive death of granulosa cells (GCs) hinders the progression of follicular growth. However, the relationship between <i>DLAT</i> and follicular growth is poorly understood. Here, we found that pyruvate significantly shortened the age of pubertal initiation in mice and promoted follicular growth by promoting the proliferation of GCs. In addition, pyruvate up-regulated the expression of <i>DLAT</i> and the high level of <i>DLAT</i> was observed in large follicles, which were associated with follicular growth. Mechanistically, <i>DLAT</i> increased the mRNA and protein levels of proliferation pathways such as <i>PCNA</i> and <i>MCL1</i> to promote GC proliferation. Additionally, DLAT bound to CASP3 and CASP9 proteins to inhibit the apoptosis of GCs. Taken together, these results reveal a mechanism that pyruvate regulated <i>DLAT</i> to promote follicular growth, and <i>DLAT</i> represents a promising target that supports new strategies for improving the growth of follicles.