PI3K/AKT signaling pathway identified as key molecular link between obesity and female infertility

Female infertility linked to obesity is a complex issue arising from the interplay of metabolic and reproductive dysfunctions. Current approaches often fall short in addressing the underlying molecular mechanisms that connect these two conditions. The Phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway is a central regulator of cellular processes, including insulin action, adipokine signaling, and ovarian physiology, making it a prime candidate for mediating this intricate connection. Understanding its role is crucial for developing more effective interventions.

This review article systematically examines the current understanding of the PI3K/AKT signaling pathway as a crucial molecular link between obesity and female infertility. It synthesizes research on how aberrant regulation of key protein and peptide mediators—including insulin, adipokines, gonadotropins, and inflammatory cytokines—impacts ovarian physiology. The authors explore the mechanistic and clinical implications of PI3K/AKT dysfunction, focusing on its role in dysfunctional follicular growth, hormonal dysregulation, and decreased endometrial receptivity.

The review highlights that in obesity, dysfunctional PI3K/AKT signaling directly contributes to impaired reproductive function. Specifically, it mediates the adverse effects of elevated insulin, dysregulated adipokines, altered gonadotropin signaling, and chronic inflammatory cytokines on ovarian health. This aberrant signaling leads to dysfunctional follicular growth, significant hormonal dysregulation, and decreased endometrial receptivity, all critical factors in female infertility.

The article emphasizes that modulation of the PI3K/AKT pathway presents a promising avenue for novel therapeutic strategies to concurrently manage both the metabolic and reproductive complications associated with obesity.