Research Paper Volume 12, Issue 20 pp 20801—20816

Synergistic effect between LH and estrogen in the acceleration of cumulus expansion via GPR30 and EGFR pathways

Jie Liu1,2, , Ru Yao1,2, , Sihai Lu1,2, , Rui Xu1,2, , Hui Zhang1,2, , Juncai Wei1,2, , Chunrui Zhao1,2, , Yaju Tang1,2, , Chan Li1,2, , Haokun Liu1,2, , Xiaoe Zhao1,2, , Qiang Wei1,2, , Baohua Ma1,2, ,

  • 1 College of Veterinary Medicine, Northwest A&F University, Yangling 712100 Shaanxi, China
  • 2 Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Yangling 712100, Shaanxi, China

Received: May 3, 2020       Accepted: July 25, 2020       Published: October 28, 2020
How to Cite

Copyright: © 2020 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The estrogen membrane receptor GPR30 (also known as G-protein coupled receptor 30) has recently been shown to be involved in the regulation of oocyte maturation and cumulus expansion. However, whether GPR30 expression is regulated by gonadotropin stimulation and how it participates in the regulation of the maturation process is still not clear. In this study, we explored the mechanism underlying the synergy between luteinizing hormone and 17β-estradiol (17β-E2) to improve the epidermal growth factor (EGF) response in cumulus oocyte complexes (COCs) during oocyte maturation in mice. The expression and distribution of GPR30, EGFR, and EGF-like growth factors were examined by real-time quantitative PCR, western blot, and immunofluorescence staining. Lyso-Tracker Red labeling was performed to detect the lysosomal activity in follicle granular cells (FGCs). Cumulus expansion of COCs was evaluated after in vitro maturation for 16 h. We found that EGF-like growth factors transmit LH signals to increase GRP30 levels by inhibiting protein degradation in lysosomes. Meanwhile, 17β-E2 stimulates the GPR30 signaling pathway to increase EGF receptor levels, enhancing the response ability of EGF signaling in COCs and thus promoting cumulus expansion. In conclusion, our study reveals the synergistic mechanism between LH and estrogen in the regulation of cumulus expansion during oocyte maturation process.


AREG: amphiregulin; BA1: bafilomycin A1; BTC: betacellulin; BSA: bovine serum albumin; CHX: cycloheximide; CCs: cumulus cells; COCs: cumulus oocyte complexes; DMEM/F12: Dulbecco’s minimum essential medium nutrient mixture F-12; DMSO: dimethyl sulfoxide; E2: estradiol; EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; EREG: epiregulin; FGCs: follicle granular cells; GPR30: G-protein coupled receptor 30, also known as the estrogen membrane receptor.; hCG: human chorionic gonadotropin; IVM: in vitro maturation; LH: luteinizing hormone; MEM-α: Minimum Essential Medium Alpha; OOs: oocytes; PBS: phosphate buffer solution; PMSG: pregnant mare serum gonadotropin; RT: room temperature; RT-qPCR: RNA extraction and quantitative reverse transcription polymerase chain reaction.