Deficiency of Pdk1 contributes to primordial follicle activation via the upregulation of YAP expression and the pro‑inflammatory response

The molecular mechanisms underlying the activation of primordial follicles are poorly understood. The serine/threonine protein kinase phosphoinositidedependent kinase 1 (PDK1), a pivotal downstream effector of phosphatidyl inositol3 kinase (PI3K) signaling, plays a vital role in cellular signaling. In order to identify the function of PDK1 in ovarian follicle development, this study used conditional Pdk1 deletion in mouse oocytes by crossing Pdk1loxP/loxP mice with transgenic mice carrying Gdf9 promotermediated Cre recombinase and found that Pdk1flx/flxGdf9Cre mice were subfertile with increased serum folliclestimulating hormone (FSH) and luteinizing hormone (LH) levels compared with Pdk1flx/flx mice. The deletion of Pdk1 in oocytes induced massive primordial follicle activation, leading to premature ovarian failure (POF). Further investigation revealed that enhanced Yesassociated protein (YAP) expression and an increased proinflammatory response also contributed to massive primordial follicle activation. PDK1 formed the complex with the core kinases of Hippo signaling and regulated the expression levels of YAP. On the whole, the findings of the present study demonstrate that PDK1 serves as an indispensable gatekeeper for maintaining the primordial follicle pool and provide a deeper understanding of POF treatment.