Acyl-CoA long-chain synthetase 1 (ACSL1) protects the endometrium from excess palmitic acid stress during decidualization.

Endometrial receptivity relies on the functional and morphological change of endometrium stromal cells (EnSCs) and epithelial cells in the secretory phase. Decidualization of ESCs and transitions in endometrium epithelial cells are crucial for successful uterine implantation and maintaining pregnancy. Accumulated data have demonstrated that decidualization is tightly coordinated by lipid metabolism. However, the lipidomic change and regulatory mechanism in uterine decidualization are still unknown. Our study showed that endometrium stromal cells and decidual stromal cells had different lipidomic profiles. Acyl-CoA long-chain synthetase 1 (ACSL1) which converts fatty acids to acyl-CoA expression was strongly elevated during decidualization. ACSL1 knockdown inhibited stromal-to-decidual cell transition and decreased the decidualization markers prolactin and Insulin-like growth factor-binding protein-1 (IGFBP1) expression through the AKT pathway. Lipid uptake was upregulated in stromal cells while lipid droplet accumulation was downregulated during decidualization. Meanwhile, silencing of ACSL1 led to impaired spare respiratory capacity, and downregulation of TFAM expression, indicating robust lipid metabolism. While palmitic acid addition impeded decidualization, overexpression of ACSL1 could partially reverse its effect. ACSL inhibitor Triacsin C significantly impeded decidualization in a three-dimensional coculture model consisting of endometrial stromal cells and epithelial cells. Knockdown of ACSL1 in stromal cells decreased the expression of the decidualization markers PAEP and SPP1 in epithelial cells. Collectively, ACSL1 is essential for uterine decidualization and protects stromal cells from excess palmitic acid stress.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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