Open AccessDeficiency of Pdk1 contributes to primordial follicle activation via the upregulation of YAP expression and the pro‑inflammatory response
Author(s) -
Jiayin Gao,
Tiefang Song,
Dehong Che,
Changmin Li,
Jing Jiang,
Jingyao Pang,
Yujuan Yang,
Hao Wang
Publication year - 2019
Publication title -
international journal of molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm.2019.4437
Subject(s) - downregulation and upregulation , oncogene , microbiology and biotechnology , biology , inflammatory response , molecular medicine , cancer research , cell cycle , apoptosis , inflammation , immunology , gene , genetics
The molecular mechanisms underlying the activation of primordial follicles are poorly understood. The serine/threonine protein kinase phosphoinositide‑dependent kinase 1 (PDK1), a pivotal downstream effector of phosphatidyl inositol‑3 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 Gdf‑9 promoter‑mediated Cre recombinase and found that Pdk1flx/flxGdf9Cre mice were subfertile with increased serum follicle‑stimulating 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 Yes‑associated protein (YAP) expression and an increased pro‑inflammatory 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.