Roles of Grp78 in Female Mammalian Reproduction

The glucose-regulated protein (GRP78) also referred to as immunoglobulin heavy chain binding protein (Bip) is one of the best characterized endoplasmic reticulum (ER) chaperone proteins, which belongs to the heat-shock protein (HSP) family. GRP78 as a central regulator of ER stress (ERS) plays many important roles in cell survival and apoptosis through controlling the activation of transmembrane ERS sensors: PKR-like ER-associated kinase (PERK), inositol requiring kinase 1 (IRE1), and activating transcription factor 6 (ATF6). Many studies have reported that GRP78 is involved in the physiological and pathological process in female reproduction, including follicular development, corpus luteum (CL), oviduct, uterus, embryo, preimplantation development, implantation/decidualization, and the placenta. The present review summarizes the biological or pathological roles and signaling mechanisms of GRP78 during the reproductive processes. Further study on the functions and mechanisms of GRP78 may provide new insight into mammalian reproduction, which not only enhance the understanding of the physiological roles but also support therapy target against infertility.