GPD1L‐Mediated Glycerophospholipid Metabolism Dysfunction in Women With Diminished Ovarian Reserve: Insights From Pseudotargeted Metabolomic Analysis of Follicular Fluid

ABSTRACT Diminished ovarian reserve (DOR) is a pathological condition characterised by reduced ovarian function, which refers to the decreased quality and quantity of oocytes, potentially causing female infertility and various health issues. Follicular fluid (FF) serves as the microenvironment for follicular development and oocyte maturation, gaining an in‐depth understanding of the metabolic state of FF will help us uncover the key biological processes involved in ovarian aging, while the specific underlying pathogenic mechanisms are not fully understood. In this study, we utilised pseudotargeted metabolomic analysis of FF to reveal the glycerophospholipid metabolism dysfunction mediated by GPD1L in DOR patients. We also found that GPD1L was downregulated in granulosa cells (GCs) of DOR patients, resulting in increased cell apoptosis and mitochondrial dysfunction. Moreover, our results demonstrated that the downregulated expression of GPD1L could induce follicular atresia and impair oocyte quality in mouse ovaries. Altogether, our research suggested that GPD1L in GCs and the key metabolites in the glycerophospholipid metabolism pathway could potentially act as novel biomarkers of DOR diagnosis, paving the way for a new theoretical basis for understanding the pathogenesis of DOR.