Chlorogenic Acid Ameliorates Ovarian Aging in Laying Chickens by Restoring Lipid Metabolism and Steroidogenesis via the ERK/PPARα Signaling Pathway

Background Ovarian aging is characterized by progressive impairments of follicular development and reproductive performance. Increasing evidence indicates that metabolic dysregulation plays a central role in the decline of ovarian function. Chlorogenic acid (CGA), a widely distributed plant-derived polyphenol, is known for its antioxidant, anti-inflammatory, and metabolic properties. However, its potential role in ovarian aging and the underlying mechanisms remain unexplored. Methods D-galactose-induced granulosa cell (GC) senescence model and naturally aging laying chickens were used for evaluating the protective effects of CGA on ovarian aging. Cellular senescence, mitochondrial function, lipid metabolism, and steroidogenic capacity were evaluated through molecular, biochemical, transcriptomic, and histological analyses. Mechanistic studies employed pharmacological inhibition and genetic knockdown to delineate the signaling hierarchy. Results In D-gal-induced GCs, CGA mitigated cellular senescence, improved mitochondrial function, and restored key steroidogenic gene expression ( STAR, CYP11A1 , and CYP19A1 ). Mechanistically, CGA reversed metabolic dysregulation by suppressing ERK1/2 phosphorylation to restore PPARα activity. This mechanism was supported by pharmacological ERK1/2 inhibition, which amplified these benefits, and siRNA-mediated PPARα silencing, which blunted CGA-induced steroidogenic recovery. In naturally aging laying chickens, CGA supplementation enhanced serum estradiol and antioxidant capacity. Crucially, CGA positively modulated the liver-ovary axis by rejuvenating hepatic lipid metabolism and systemic transport, thereby promoting yolk deposition, follicular development, and egg-laying performance. Conclusion These findings suggest that CGA mitigates ovarian aging by coordinating mitochondrial homeostasis, lipid metabolism, and steroidogenesis via the ERK/PPARα pathway. The result provides mechanistic insight into the potential of plant-derived polyphenols as metabolic regulators for preserving ovarian function.